Note: Descriptions are shown in the official language in which they were submitted.
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OPIOID + DEVICE COMBINATION PRODUCTS WITH IMPROVED SAFETY AND
EFFICACY PROFILES
CROSS REFERENCE TO RELATED APPLICATIONS
[0001] This application claims benefit of U.S. Provisional Patent
Application No.
62/294,585 filed on February 12, 2016, U.S. Provisional Patent Application No.
62/325,012 filed
on April 20, 2016, U.S. Provisional Patent Application No. 62/375,192 filed on
August 15, 2016,
U.S. Provisional Patent Application No. 62/375,256 filed on August 15, 2016,
U.S. Provisional
Patent Application No. 62/416,972 filed on November 3, 2016, U.S. Provisional
Patent
Application No. 62/427,919 filed on November 30, 2016, U.S. Provisional Patent
Application
No. 62/432,292 filed on December 9, 2016, U.S. Provisional Patent Application
No. 62/432,248
filed on December 9, 2016, U.S. Provisional Patent Application No. 62/432,358
filed on
December 9, 2016, U.S. Provisional Patent Application No. 62/432,394 filed on
December 9,
2016, and International Patent Application No. PCT/U516/46491 filed on August
11, 2016;
which are incorporated herein by reference in their entirety to the full
extent permitted by law.
FIELD OF THE INVENTION
[0002] The present disclosure relates to a novel system, each independent
component
which brings a unique attribute, that together as a drug + device combination
product improves
the opioid's drug/safety profile and deters/decreases opioid overdoses,
misuse, abuse, accidental
ingestion, and opioid divergence. Each opioid drug + device combination
product is comprised
of an opioid, an interrelated Opioid Specific and Patient Tailored APPTM, an
overdose diagnostic
(OverDoseScreenTm), opioid specific and patient tailored dispensing algorithm,
drug dispenser,
drug cassette, electronic data exchange, and certain integrated support
services. The closed loop
system is designed to decrease opioid diversion, misuse, abuse, addiction,
dependence, overdose,
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accidental ingestion and deaths ¨ thereby improving the quality of care,
enhancing the patient's
quality of life, and decreasing the total cost of care by minimizing the
number of opioid related
medical interventions, emergency room visits, and hospitalizations.
BACKGROUND OF THE INVENTION
[0003] Deterring opioid divergence, misuse, decreasing the incidence of
opioid addiction
and dependence, avoiding opioid overdoses and deaths, decreasing the incidence
of accidental
ingestion of opioids by children, properly titrating and dosing patients,
optimizing treatment,
effectively managing opioid tolerance, avoiding unnecessary opioid induced
side effects, and
ensuring patient prescription compliance, and controlling opioid withdrawal
represent major
unmet needs.
[0004] According to the United Nations Office on Drugs and Crime (UNODC),
drug
overdose is the top cause of drug-related deaths in the world, and opioids are
the top drug type
associated with those deaths. Opioids are derived from opium, which comes from
opium poppy
seeds. In general, the term opioid is used to refer to synthetic prescription
painkillers, but heroin
is also an opioid. The following are commonly prescribed opioids with example
brand names of
established and new products: (i) Oxycodone (OxyContin()), (ii) Hydrocodone
(Vicodinc)), (iii)
Morphine, (iv) Buprenorphine, (v) Hydromorphone (Dilaudidc)), (vi) Oxymorphone
(Opanac)),
Tapentadol, (vii) Tramadol (Ultramc)), (viii) Fentanyl (Duragesicc)),
methadone (Dolophinec)),
Morphine Sulfate and Naltrexone Hydrochloride (Embedac)), Oxycodone
Hydrochloride and
Naltrexone Hydrochloride (Troxyca ER), etc.
[0005] The World Health Organization (WHO) estimated that 16.4 million
people used
opioids in 2012. People who take prescription painkillers can become addicted
with just one
prescription. Once addicted, it can be hard to stop. According to the National
Institute on Drug
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Abuse (NIDA), combined with their highly-addictive nature, opioids are
dangerous because a
single large dose can cause severe respiratory depression and death. In
addition, a drug user's
tolerance to opioids decreases during breaks from drug use. When they take the
drug at the same
dose as they did before a break, it often leads to an overdose.
[0006] According to the International Narcotics Control Board (INCB), North
America
consumes 80 percent of the world's opioids, and has the highest rate of drug-
related deaths in the
world. IMS Health reported that Americans accounted for 99 percent of the
world's
hydrocodone (Vicoding) consumption, 80 percent of the world's oxycodone
(Percocet and
Oxyconting) consumption and 65 percent of the world's hydromorphone
(Dilaudidg)
consumption in 2014.
[0007] The United States' opioid statistics are alarming:
a. According to the National Institute of Drug Abuse, opioid abuse is an
epidemic
in the United States, with about five (5) percent of the adult population
using
opiate pain medications non-medically. In 2015, approximately 12.5 million
people misused prescription pain relievers in the past year, representing 4.7
percent of the population aged 12 or older.'
b. Major causes of preventable death ¨ like car accidents ¨ have been on the
decline, but deaths from drug abuse doubled in the last decade (Deaths by
overdoses involving prescription painkillers quadrupled since 1999.). More
people die from overdoses of prescription opioids than from all other drugs
1 Prescription Drug Use and Misuse in the United States: Results from the 2015
National Survey on Drug Use and
Health, SAMHSA: Arthur Hughes, Matthew R. Williams, Rachel N. Lipari, and
Jonaki Bose; RTI International:
Elizabeth A. P. Copello and Larry A. Kroutil, September 2016.
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combined, including heroin and cocaine.2 In 2014, there were 18,893 overdose
deaths related to prescription pain relievers ¨ 52 people per day.3 Opioid
painkillers are the leading cause of accidental death.
c. In 2015, 2.1 million people aged 12 or older were recent initiates for pain
reliever misuse (i.e., misused for the first time in the past year), an
average of
5,753 per day.4
d. In 2015, 2.0 million people had a pain reliever use disorder;
e. Most adolescents who misuse prescription pain relievers are given them for
free
by a friend or relative.5
f In 2014, 467,000 adolescents, aged 12 to 17, were current nonmedical users
of
pain relievers, with 168,000 having an addiction to prescription pain
relievers.6
g. According to the CDC, each day, almost 7,000 people are treated in
emergency
room (ER) for using opioids in a manner other than as directed (That equates
to
2.6 million people annually. Of these, more than 1.4 million ER visits were
related to prescription drugs).
h. There are 420,000 prescription opioid overdose ER visits annually.' Fifty
five
percent (55%) result in hospitalizations (on average 3.8 days) costing on
2 National Institute of Drug Abuse. (2015). Drug Facts: Prescription and Over-
the-Counter Medications. Bethesda,
MD: National Institute of Drug Abuse.
3 CDC
4 Prescription Drug Use and Misuse in the United States: Results from the 2015
National Survey on Drug Use and
Health, SAMHSA: Arthur Hughes, Matthew R. Williams, Rachel N. Lipari, and
Jonaki Bose; RTI International:
Elizabeth A. P. Copello and Larry A. Kroutil, September 2016.
Prescription Drug Use and Misuse in the United States: Results from the 2015
National Survey on Drug Use and
Health, SAMHSA: Arthur Hughes, Matthew R. Williams, Rachel N. Lipari, and
Jonaki Bose; RTI International:
Elizabeth A. P. Copello and Larry A. Kroutil, September 2016.
6 Substance Abuse and Mental Health Services Administration, Center for
Behavioral Health Statistics and Quality.
(2015). Behavioral health trends in the United States: Results from the 2014
National Survey on Drug Use and
Health. Rockville, MD: Substance Abuse and Mental Health Services
Administration.
7 CDC
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average $29,500; 45% treated in the ER for an average cost of $3,600.8 Direct
medical costs related to ER prescription opioid overdose visits equal >$7.5
billion annually - >$25 billion in total medical costs annually (including ER
costs).
= 91% of opioid overdose patients get another opioid prescription, most
from
the same doctor.
= 7% overdose again within 12 months.
= 14% overdose again within 24 months.
o 17% of high-dose patients overdose within 24 months, equal to
10.7% of total annual overdose patients.
i. Opioid abusers have healthcare costs that are nearly nine times higher
than non-
abusers.
j. Three studies estimated the United States economic burden of the opioid
epidemic at around $55 billion annually.
= In the United States, prescription opioid abuse costs were about $55.7
billion in 2007. Of this amount, 45%, $25 billion, to healthcare costs (e.g.,
ER visits and treatment costs), 46% was attributable to workplace costs
(e.g., lost productivity), and 9% to criminal justice costs.9
= Hansen's study attributed 79 percent of the costs to lost productivity
($42
billion), 15 percent to criminal justice costs ($8.2 billion) and only six
8 Substance Abuse and Mental Health Services Administration, Center for
Behavioral Health Statistics and Quality.
(2015). Behavioral health trends in the United States: Results from the 2014
National Survey on Drug Use and
Health. Rockville, MD: Substance Abuse and Mental Health Services
Administration.
9 Alabama Teen Challenge, Prescription Painkiller Overdose Epidemic In US
https://alatc.org/prescription-painkiller-
overdose-epidemic-in-us/
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percent to medical costs, comprising four percent for drug abuse treatment
($2.2 billion) and two percent for medical complications ($944 million).10
= In Birnbaum's study, healthcare costs, defined more broadly, accounted
for
45 percent ($25.0 billion) of the total, while workplace costs accounted for
46 percent ($25.6 billion) and criminal justice costs for only 9 percent ($5.1
billion)." The medical expense number correlates with the estimated costs
per h above.
Regardless of the cost allocations, the burden to the United States healthcare
system
and federal, state, and local governments is significant and growing.
[0008] This is a worldwide problem. As examples, according to the Canadian
Centre on
Substance Abuse (CCSA), Canada ranked second, behind the United States, for
the highest
opioid consumption per capita in the world. In Europe, deaths from heroin
declined, but deaths
from synthetic opioids rose. Estonia saw one of the worst increases in
prescription opioid deaths
in the world, with a 38 percent increase from 2011-12. In New Zealand, opioid
abuse is on the
rise, and more than 1.2 million people abuse opioids ¨ primarily prescription
painkillers. In
South America, a continent known for its production and trafficking of illicit
drugs, opioid abuse
is low in most countries. However, Costa Rica reported about 2.8 percent of
the population
abuses prescription painkillers.
[0009] Many problems regarding prescription drug abuse arise when doctors
prescribe
highly-addictive drugs in too large of dosages or prescribe drugs based on
inaccurate diagnoses.
Increased scrutiny of doctors leads to another problem. Some doctors do not
prescribe
Ryan N. Hansen, et al., "Economic Costs of Nonmedical Use of Prescription
Opioids," Clinical Journal of Pain 27,
no. 3 (2011): 194-202, doi:10.1097/AJP.0b013e3181ff04ca.
11 Howard G. Birnbaum, et al., "Societal Costs of Prescription Opioid Abuse,
Dependence and Misuse in the United
States," Pain Medicine 12, no. 4 (2011): 657-67, doi:10.1111A.1526-
4637.2011.01075.x.
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medications in high enough doses because of the fear of addicting their
patients or because of
fear of scrutiny from other doctors and/or government agencies.
[00010] Unfortunately, the population that most often suffers from chronic
pain is also one
of the most vulnerable to addiction. The elderly is one of the biggest groups
of prescription drug
addicts in the United States. Doctors wrote 55 million, 21 percent of the 260
million opioid
prescriptions, for people 65 and older, in 2013, a 20 percent increase from
the prior five years.
The Substance Abuse and Mental Health Services Administration (SAMHSA) found
that the
number of seniors misusing or dependent on prescription pain relievers rose to
336,000 in 2012,
up by 132,000 since 2002. From 2007-11, visits to the emergency room caused by
the misuse of
pharmaceuticals by people older than 65 climbed 50 percent.
[00011] Exemplifying the misconception regarding the safety of
prescriptions, a SAMHSA
survey found more than half of the people aged 12 and older who abused
prescriptions in 2012-
13 got the drugs from friends or family members for free.
[00012] A NIDA survey found about one out of every 12 high school seniors
admitted to the
nonmedical use of Vicodin and one out of every 20 admitted to abusing
OxyContin in 2010.
SAMHSA found 2.2 percent of youths aged 12 to 17 used prescription drugs for
nonmedical
purposes, and 1.7 percent used pain killers for nonmedical purposes in 2013.
That's more than
hallucinogens (0.6 percent), cocaine (0.2 percent) and heroin (0.1 percent)
combined.
[00013] Avoiding unnecessary medical complications or death by ensuring a
drug is
efficacious for the patient and that the patient is compliant and persistent
with their
prescription(s) represents a major unmet need and a trillion-dollar global
market opportunity ¨
this is larger than the global pharmaceutical industry. As an example, Express
Scripts, the
largest pharmacy benefit manager in the United States, found only 25 to 30
percent of
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medications are taken per the Prescriber's instructions (adherence)... and of
those taken, only 15
to 20 percent are refilled per the Prescriber's instructions (persistence).
This lack of adherence
and persistence is estimated to result in more than $300 billion being wasted
annually for the
treatment of unnecessary medical complications in the United States.
[00014] Drug-related hospitalizations account for 2.4 to 6.5 percent of all
medical
admissions in the general population. A meta-analysis found a fourfold
increase in the rate of
hospitalization related to adverse drug events (ADE) in older adults compared
with younger
adults (16.6 versus 4.1 percent). Myriad factors in older individuals
contribute to their increased
risk for developing a drug-related problem. These include frailty, coexisting
medical problems,
memory issues, polypharmacy, and the use of non-prescribed medications.
Estimates indicate
that 88 percent of the ADE hospitalizations among older adults were
preventable, compared with
24 percent among young persons.
[00015] Prescription opioid overdoses in the United States illustrates the
cost savings
potential of controlled medication prescribing12. According to the CDC
(Centers for Disease
Control and Prevention), there are 420,000 prescriptions opioid overdose ER
visits and 16,000
Rx opioid overdose deaths annually. Fifty-five (55) percent result in an
average 3.8 days of
hospitalization at an average cost of approximately $30,000. The remaining 45
percent of
patients run up an average $3,600 per ER visit. That equates to an average
cost of $18,000 per
ER Rx opioid overdose annually ¨ a total direct cost of $7.5 billion. If total
medical costs for
additional physician visits, addiction treatment, etc. are factored in, the
medical costs, including
the $7.5 billion, exceed $25 billion annually. This estimate correlates well
with other estimates
of direct medical costs associated with prescription overdose abuse.
12 Sources: CDC; Presentation of Prescription and Nonprescription Opioid
Overdoses to US Emergency
Departments, JAMA Intern Med. 2014;174(12):2034-2037.
doi:10.1001/jamainternmed.2014.5413; Societal costs
of prescription opioid abuse, dependence, and misuse in the United States.
Pain Medicine 2011; 12: 657-667
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[00016] Optimizing drug therapy is an essential part of medical care. The
process of
prescribing a medication is complex and includes (i) deciding that a drug is
indicated, (ii)
choosing the best drug, (iii) determining a dose and schedule appropriate for
the patient's
physiologic status, (iv) monitoring for effectiveness, tolerance and toxicity,
(v) educating the
patient about expected side effects, and (vi) indications for seeking
consultation.
[00017] Avoidable adverse drug events (ADEs) are the serious consequence of
(i)
inappropriate drug prescribing, (ii) changes in the patient's reaction to the
drug over time due to
increased tolerance, lifestyle, other medications, other medical conditions,
worsening medical
condition, or changes in the patients overall well-being, etc., or (iii)
addition of new prescription
or OTC medications, vitamins, dietary supplements, herbal medicines (e.g.,
ginseng, ginkgo
biloba extract, glucosamine, St. John's wort, echinacea, garlic, saw palmetto,
kava, and valerian
root), and/or recreational drugs, etc. Often, clinicians do not question
patients about use of
herbal medicines and patients do not routinely volunteer this information.
Furthermore, most
patients do not inform their clinician that they were using unconventional
and/or recreational
medications. A study of the use of 22 supplements in a survey of 369 patients
aged 60 to 99
years found potential interactions between supplements and medications for ten
of the 22
supplements surveyed. As a result, any new symptom should first be considered
to be drug-
related until proven otherwise.
[00018] Prescribing for older patients, who consume the most medications
per capita,
presents unique challenges. Premarketing drug trials often exclude geriatric
patients and
approved doses may not be appropriate for older adults. Many medications need
to be used with
special caution because of age-related changes in pharmacokinetics (i.e.,
absorption, distribution,
metabolism, and excretion) and pharmacodynamics (the physiologic effects of
the drug).
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[00019] Larger drug storage reservoirs and decreased clearance prolong drug
half-lives and
lead to increased plasma drug concentrations in older people. Particular care
must be taken in
determining drug dosages. The proportional increase in body fat relative to
skeletal muscle that
generally accompanies aging may result in the increased volume of drug
distribution. Decreased
drug clearance may also result from the natural decline in renal function with
age, even in the
absence of renal disease.
[00020] The same dose could lead to higher plasma concentrations in an
older, compared to
younger, patient. For example, the volume of distribution for diazepam is
increased, and the
clearance rate for lithium is reduced, in older adults. From the
pharmacodynamic perspective,
increasing age may result in an increased sensitivity to the effects of
certain drugs, e.g., opioids
and benzodiazepines. Prescription Opioid overdose deaths often involve
benzodiazepines.
[00021] The use of greater numbers of drug therapies has been independently
associated
with an increased risk for an adverse drug event, irrespective of age, and
increased risk of
hospital admission. Polypharmacy is of particular concern in older people who,
compared to
younger individuals, tend to have more disease conditions for which therapies
are prescribed.
Approximately half of the patients taking drugs take two medications and 20
percent five or
more. As an example, one study found that among ambulatory older adults with
cancer, 84
percent were receiving five or more and 43 percent were receiving 10 or more
medications.
[00022] The risk of an adverse event due to drug-drug interactions is
substantially increased
when multiple drugs are taken.
[00023] Periodic evaluation of a patient's drug regimen is an essential
component of medical
care. However, a survey of Medicare beneficiaries found that more than 30
percent of patients
reported they had not talked with their doctor about their different
medications in the previous 12
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months. Furthermore, when these reviews are done, they often overlook OTC,
supplements,
herbal medicines and recreational drugs that are being taken by the patient.
[00024] Multiple factors contribute to the appropriateness and overall
quality of drug
prescribing. These include avoidance of inappropriate medications, appropriate
use of indicated
medications, monitoring for side effects and drug levels/opioid tolerance,
avoidance of drug-drug
interactions, monitoring for increasing medication tolerance and involvement
of the patient and
integration of patient values. Current measures of the quality of prescribing
generally focus on
one or some of these factors, but rarely on all.
BRIEF SUMMARY OF THE INVENTION
[00025] The present invention describes a novel integrated system of an
opioid, tamper
resistant drug dispensing device, related drug cassette, firmware, software,
biometric logon, a
drug specific and/or patient tailored App, an opioid overdose diagnostic
screen
(OverDoseScreenTm), opioid specific dose dispensing algorithm, electronic
communications,
data analytics, and integrated support. The system, processes and methods are
integrated
together so as a whole they ensure: 1) the opioid is only dispensed to or (in
the case of a minor)
for the patient for whom the opioid is prescribed (avoid divergence); 2) the
opioid is efficacious
for the patient; 3) the opioid is properly titrated to achieve the best
therapeutic dose; 4) the opioid
is the right dose to control the patient's pain; 5) the dispensed opioid dose
will not overdose the
patient, 6) the prescriber has the requisite drug specific digitally captured
and/or patient self-
assessment and/or self-test and/or self-reported physiological, psychological,
lifestyle,
concurrent medications, and environmental information (values) to manage
opioid dosing, and/or
tolerance and/or side effects; 7) that in the case of withdrawing the patient
from an opioid, that
the withdrawal is properly managed; 8) that the prescription is only written,
filled, and dispensed
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by authorized medical professionals; 9) that the dispensing of each dose is
controlled to preclude
dispensing if:
i. the patient is trying to take the medication sooner than the prescribed
interval,
ii. the algorithm deduces that taking the drug may result in an adverse
event, e.g., a
drug-drug interaction or overdose, even if it could otherwise be dispensed
within
the prescription's dosing instructions,
iii. the drug is past its expiration/beyond-use date,
iv. the prescription dispensing period has expired,
v. the drug was not stored properly, e.g., within the right temperature
and/or humidity
guidelines,
vi. the drug batch has been recalled, and/or
vii. the patient is trying to double dose or if he/she is trying to take
the same prescribed
dose from more than one dispenser at the same time (misuse and/or abuse).
[00026] It is designed to improve the opioid's safety and efficacy profile
by assisting the
prescriber in managing patient specific opioid tolerance, opioid induced side
effects, e.g., opioid
induced constipation, and prescription compliance and persistence through the
use of digitally
captured and/or patient inputted self-assessment, self-test, and/or self-
reported information at the
point of dispensing when an opioid dose is dispensed or dispensing is
attempted by the patient.
This is one time and or trended information (values) which are made available
to the patient
and/or prescriber via on demand reports that show the relationship between
medication dosing
and certain tracked values/side effect information, e.g., medication
effectiveness.
[00027] The system functions as if the patient's physician was with the
patient asking
questions and making the requisite drug related observations and dispensing
decisions each time
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the patient attempts to dispense a prescribed opioid dose. In this way, by
increasing the drug's
efficacy/safety profile, the integrated dispensing system improves the quality
of care and the
patient's quality of life while saving the healthcare system money by: (i) in
precluding overdose
deaths, (ii) emergency room visits, (iii) hospitalizations, and (iv) physician
and allied healthcare
professional interventions while decreasing the incidence of drug related side
effects, addiction
and dependence.
[00028] The novel Opioid Specific and Patient Tailored App, which can be
operated from a
standalone drug dispensing device and/or interface device (smartphone, tablet
and/or computer,
etc.) with Bluetooth, Wi-Fi, and/or Internet communication capabilities, reads
and aggregates; (i)
the prescription information, (ii) drug storage requirements, (iii)
Prescriber's name, unique
government issued identification number, and, if applicable, DEA number (or
similar
government control number), (iv) the drug label information from the drug
cassette, (v) the drug
cassette's unique serial number, (vi) the dispensing device's unique serial
number, (vii) storage
temperature and humidity readings, (viii) unauthorized attempts to open the
dispenser since last
dispensed dose, (ix) the date and time of the last dispensed dose, (x) digital
data generated by
wearable devices, consumed, implanted, or ingested diagnostic devices,
monitoring devices,
machines, instruments, gadgets, contraptions, apparatuses, utensils,
implements, tools,
mechanisms, smartphones, digital cameras, and informalgizmos, etc., (xi)
patient self-assessment
data from input screens on the standalone dispenser or interface device
(smartphone, tablet,
and/or computer, etc.), (xii) patient self-test information/data from input
screens on the
standalone dispenser and/or interface device (smartphone, tablet, and/or
computer, etc.) and (xiii)
self-reported information from query screens, digital diaries (e.g., Apple
iPhone Health App),
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and/or from input screens on the standalone dispenser and/or interface device
(smartphone,
tablet, and/or computer, etc.)
[00029] The novel Opioid Specific and Patient Tailored App incorporates an
opioid specific
HIPPA and/or similar healthcare information protection legislation and
guidelines compliant
Opioid Specific Dispensing Algorithm which uses encrypted communications to
control the drug
dispensing device and to communicate with the patient, the centralized data
servers, and the
Integrated Support Center and/or designated Prescribers, physicians,
caregivers, and/or family
members. The algorithm uses the prescription information, dispensing device
information, drug
cassette information, Prescriber's DEA and/or unique identifier number,
digitally captured and/or
patient inputted self-assessment, and/or self-test, and/or self-reported
physiological,
psychological, lifestyle, concurrent medications being taken and/or
environmental data
(digitalized information and/or values), in a novel drug specific diagnostic
algorithm to decide if
the drug dispenser should dispense the opioid or keep the dispenser from
dispensing the opioid
by keeping the tamper resistant dispensing unit locked.
[00030] The Opioid Specific Dispensing Algorithm utilizes an incorporated
opioid specific
overdose screen diagnostic, OverDoseScreenTM, to ascertain if the opioid dose
should be
dispensed or if it should not be dispensed, even if it would otherwise be
allowed by the
prescription. The opioid specific overdose screen diagnostic is specific to
each opioid and each
opioid formulation. The objective of the opioid specific overdose screen
diagnostic is to
decrease opioid overdoses.
[00031] The novel integrated system is designed to be able to use various
drug dispenser
configurations, designs, and sizes. They can be limited to a single drug or
configured to dispense
multiple drugs. The drug dispenser can be a disposable unit or a reusable
unit. Regardless, dose
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dispensing from each drug dispenser is controlled by an Opioid Specific and
Patient Tailored
App. The App can be resident on a standalone version of the drug dispenser or
can reside on an
interface device (e.g., smartphone, computer, tablet, etc.). The following
describe disposable
versus reusable drug dispensers.
[00032] The disposable drug dispensing device (Disposable Drug Dispenser)
is designed to:
(i) fit in a pants pocket and/or purse, (ii) be water, and dust resistant,
(iii) withstand being
dropped and/or banged, (iv) operate and withstand hot and cold temperatures
within defined
temperature ranges, (v) be powered by a battery with a life equal to or
greater than the opioid's
expiration date, (vi) have a drug cassette containing an opioid that docks
into the dispenser
housing, (vii) have a tamper resistant dispenser housing that becomes an
integral unit with no
access to the opioid in the drug cassette except for when the single opioid
dose is dispensed,
(viii) remain locked from dispensing unless the dispensing device receives an
encrypted signal
authorization from the Opioid Specific App to dispense a dose, (ix) one click
dose dispensing.
When the drug dispensing device effectuates a secure handshake with the Opioid
Specific App,
the drug dispenser transmits: (i) its serial number, (ii) the current and
historic temperatures and
humidity levels since the last dispense, (iii) any alerts regarding attempts
to open the drug
dispenser since the last opioid dose was last dispensed, (iv) any drug
dispensing error messages
since the drug was last dispensed, and (v) the date and time the last opioid
dose was last
dispensed. The drug dispensing device can be configured to dispense one or
more drugs from a
single drug cassette.
[00033] The reusable drug dispensing device (Reusable Drug Dispenser) is
designed to: (i)
fit in a pants pocket (for single opioid units) and/or purse and/or belt
holster (single or multiple
drug dispensers), (ii) be water, and dust resistant, (iii) withstand being
dropped and/or banged,
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(iv) operate and withstand hot and cold temperatures within defined
temperature ranges, (v) be
reusable, (vi) be powered by a replaceable and/or rechargeable battery, (vii)
have a drug cassette
containing the opioid only be able to be docked or removed by an authorized
healthcare
professional, (viii) have a tamper resistant dispenser housing that becomes an
integral unit with
no access to the opioid in the drug cassette except for when the single opioid
dose is dispensed,
(ix) remain locked from dispensing unless the dispensing device receives an
encrypted signal
authorization from the Opioid Specific App to dispense a dose, and (x) one
click opioid
dispensing. When the drug dispenser effectuates a handshake with the Opioid
Specific App, the
drug dispenser transmits: (i) its serial number, (ii) the drug information on
the drug cassette, (iii)
the current and historic temperatures and humidity levels since the last
dispense, (iv) any alerts
regarding attempts to open the drug dispenser since the last opioid dose was
last dispensed, (v)
any drug dispensing error messages since the opioid was last dispensed, and
(vi) the date and
time the last opioid dose was last dispensed. The drug dispensing device can
be configured to
dispense one or more drugs from a single drug cassette or from more than one
cassette when
multidrug dispensing devices are used.
[00034] The single drug dispensing device is controlled by a single App.
[00035] The multi-drug dispensing units utilize multiple drug cassettes
(one each per drug)
which are controlled by a consolidation App that combines the individual drug
Apps into a single
user interface to eliminate duplication of inputs and to facilitate one click
drug dispensing for
one or more medications. The handshake between Apps is controlled by the
biometric security
system.
[00036] The single Opioid Specific App, as well as the multi-drug App,
require biometric
sign on by the patient and utilize a drug specific decision tree algorithm and
drug specific
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diagnostics and/or digitally captured and/or patient entered self-assessment,
and/or self-test,
and/or self-reported physiological, psychological, lifestyle, concomitant
medications, and/or
environmental information (data/values) to make dispensing decisions. An
encrypted biometric
sign on and/or alternative sign on include but are not limited to an iris
scan, a Logon Name and
Password, finger print scan, unique sequence of hand movements, voice control,
face scan,
unique phrases, a unique code sent to the patient's mobile phone, etc.
[00037] Once the biometric logon has been effectuated and the required
information for the
dispensing diagnostic has been captured, if everything is within normal
ranges, then the patient is
given a message to dispense the opioid and/or related medications with one
click on the drug
dispensers control button. No further communication with the patient are
required.
[00038] However, if the algorithm ascertains that it has to keep the
dispensing device locked
and not to dispense, even if within prescribing guidelines, then a number of
alternative messages
are shown on the dispensing device's and/or interface device's screen(s).
These range from
telling the patient that the requested opioid dose is not authorized by the
prescription for a
specified period of time to a message indicating that a dose, even within the
prescription dosing
schedule parameters, should not be taken without first talking with the
integrated support center
or the prescribing healthcare professional. The App facilitates calling the
support center using a
single click on the alert window. The Integrated Support Center is able to
triage the inquiry to a
physician, payer defined disease management support center, or can serve as a
disease
management and/or as medical support center for patients.
[00039] The App uses the biometric sign on and encrypted communications
with the data
center's servers and the support center to document and communicate to the
appropriate parties
(Integrated Support Center, care givers, authorized family members, etc.)
that, for example, (i)
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the patient may be heading for an undesired event, (ii) that the prescription
should be changed,
(iii) the drug may have to be changed based upon efficacy concerns, (iv) the
patient has
attempted to dispense an opioid dose early too many times (depends on the
opioid), (iv) appears
to be following a misuse or an abuse pattern, etc., (v) is not following
prescribing guidelines, and
(vi) is failing to take the medication, etc.
[00040] The App is unique to each drug and/or each patient. Certain
algorithm interface
screens may be selected by the Prescriber to capture information, on a defined
schedule or
sequence, to allow for better patient management and to individualize drug
therapy. These
screens may or may not be utilized by the Drug Dispensing Algorithm to make a
dose dispensing
decision. As an example, the Prescriber may indicate that the App presents a
pain self-
assessment screen to track the effectiveness of the opioid to control the
patient's pain and to
monitor for increasing opioid tolerance; for stool consistency (self-reported)
and/or for the
frequency of bowel (self-reported) movements to ascertain if the patient is
moving towards
opioid induced constipation, and/or an Sp02 (blood oxygen saturation self-
test) to ascertain if
the opioid is leading to a depressed respiratory rate, etc. and/or pulse rate
(digitally captured) as
part of the dispensing procedure.
[00041] A prescriber may request the constipation self-reporting
information to enable the
algorithm to: 1) make a dispensing decision and/or 2) alert the patient that
he/she appears to be
getting constipated and that the patient should consider taking a laxative,
and/or 3) to
recommend the patient consult the support center to ascertain if it would be
advisable to take a
laxative, and/or 4) to advise the prescriber that the patient is showing signs
of opioid induced
constipation, etc. Another example would be the Prescriber designating that
the App require a
speech self-test and/or a cognition self-test and completion of a concomitant
medications taken
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self-report, etc. as part of the dispensing request procedure. The Prescriber
would use this
particular information to preclude a potential drug-drug interaction, etc. The
respective screens
may be presented every time before dispensing or based upon a defined interval
or as a result of
a digital reading or other screen input, etc., as defined by the Prescriber.
[00042] The Prescriber can also designate that certain opioid specific side
effect information
be tracked via specific side effect input screens, even if they will not be
required by the
dispensing algorithm, to better manage the patient. If the Prescriber chooses
to track a side effect
or multiple side effects, the Prescriber can designate how often each should
be tracked, e.g.,
every time before a dose is dispensed, once per day, once per week, when a
tracked value
exceeds or is lower than a specified range, etc.
[00043] The prescription information and Prescriber designated side-effect
tracking
information can either be automatically digitally uploaded or manually entered
into the Opioid
Specific and Patient Tailored App. The system generally calls for utilization
of a novel
Prescription API (Application Program Interface) to allow the Prescriber to
avoid having to enter
information twice, once for the prescription and once for the Opioid Specific
App. The API
syncs the data input interface with the e-prescribing programs (e.g., ADSC
MedicsRx, Allscripts,
DAW Systems, DrFirst Rcopia, MDT Toolbox-Rx, Medtab RxCure, OA Systems,
Practice
Fusion, RxNT eRx, Spectra eRx, etc.) and/or pharmacy prescription systems
(e.g., OmniCare,
QS/1, PharMerica, Frameworks, etc.) and/or Electronic Prescribing Networks
(e.g., SureScripts -
that seamlessly connects Prescribers with Pharmacies) eliminating duplicate
entries. The
Prescription API enables the Prescriber to prescribe his/her additional
information capture and/or
side effects tracking and their respective tracking frequencies and to input
patient authorized care
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giver and medical professional alert notification authorizations and their
related contact
information.
[00044] Eliminating duplicate inputs may also be facilitated via the
integration of data
through the utilization of a network, such as SureScripts Electronic
Prescribing Network, which
seamlessly connects physicians with pharmacies. The networks allow the secure,
reliable
transmission and delivery of electronic prescription orders and renewal
authorization requests
between computers at the pharmacy and computers at the physician's office.
Simultaneous
transmission to the Patient Database resident on the Central Servers can be
accommodated.
[00045] Upon submission of the electronic prescription, which can also
happen at the
pharmacy from a written prescription, the information from the prescription
interface is sent to
the Patient Database resident on the Central Servers. Upon receipt, the Opioid
Specific and
Patient Tailored App generation program creates a patient specific database
and generates certain
authorization codes (e.g., patient identifier record number, dispenser opening
code for reusable
drug dispensers, etc.), link the prescription, patient, and pharmacy to the
App, and then
automatically generate the patient and Opioid Specific App, a copy which is
retained on the
Central Server. Then, the program automatically sends an email and/or text
message to the
Patient with an App download link. A click on the link, or copying the link to
the navigation bar
on the Internet browser, will take the patient to the patient and Opioid
Specific App download
page. Clicking on the "download button" automatically downloads the App to the
interface
device. Once the patient downloads the Opioid Specific and Patient Tailored
App, they will
receive a separate email with a unique Patient Identification Number. At that
point, the Patient
will be able to marry the Opioid Specific App with the drug dispenser. The
updates can also be
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accomplished via a wireless connection and via a wireless connection or a USB
cable interface
for multi-drug reusable drug dispensers, etc.
[00046] For reusable drug dispensers, this is a procedure that would
normally be done when
the pharmacy plugs in the USB cable to power the mechanical open and close
locking
mechanism on the drug dispenser and which is required to enter the medical
professional
restricted Dispenser Opening Code (the reusable opioids drug dispenser can
only be loaded by an
authorized medical professional).
[00047] The initial click on the App requires the Patient to provide their
Patient
Identification Number which was previously emailed to them, certain personal
information,
establish the biometric certification baseline, and tech support password and
challenge questions
information. Upon completion, the Patient will be able to use the biometric
log on to access the
drug dispensing algorithm. If this fails, they can request a password reset or
can contact the
Integrated Support Center for Tech Support to provide a temporary password
once the patient
properly answers certain challenge questions. If required, the Integrated
Support Center can
enable the patient to dispense an opioid dose while they work with the patient
to troubleshoot
their biometric log on problem. The Integrated Support Center can be contacted
by clicking on
the dial button on the alert screen of the Opioid Specific and Patient
Tailored App or by calling
the number listed for the Integrated Support Center.
[00048] The App allows the patient to ask certain questions regarding when
they took their
last opioid (or medications for multidrug dispensers), how much medication is
left, when their
next dose is due, the medication's expiration/beyond-use date, and the drug's
package insert
information, etc. It further provides access to personalized analytical
charts, some which may be
downloaded from the Integrated Support Center's servers or created by the App
from the limited
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information stored by the App, to show how the patient's symptoms are affected
when the
patient takes an opioid dose over time. This is designed to aid in patient
prescription persistence,
reinforce the importance of prescription compliance, and assist the patients
in discussions with
the prescriber related to pain management and any opioid tolerance and/or side
effect issues
(depends on the types of information the prescriber designates be tracked).
[00049] The Integrated Support Center's IT system (data servers) stores
authorized log on
information, all App history data and enables the continual update/syncing of
the App history on
all the patient's devices where the Opioid Specific and Patient Tailored App
has been
downloaded. The centralized servers are also designed to: (i) via the
Internet, update individual
App software as required, (ii) update the patient's electronic medical record
resident on the
Central Servers, (iii) to, on a real time basis, update the Integrated Support
Center's patient
specific counselor screens, (iv) conduct metadata analysis on both the
patient's individual data as
well as analysis that may include information from the patient's electronic
medical record, as
well as de-identified patient data from other patients that share similar
clinical profiles, (v) carry
out comparative patient analysis against metadata across a patient population
with similar
characteristics, etc. The analytical output is designed to assist the
Integrated Support Center
and/or payer specified disease management group(s) and/or the patient's care
givers in their
counseling of the individual patient as well as any reporting and contacts
with the Prescriber,
patient and/or payer designated disease management center and/or the patient's
physician, etc.
[00050] The Integrated Support Center IT systems are designed to allow the
Integrated
Support Center, via the patient's Opioid Specific App, (i) to change a
patient's prescription based
on an authorized Prescriber's instructions, (ii) lock the dispenser if
tampering is suspected (and
to follow the established patient, Prescriber and/or disease management
protocol to ascertain the
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next step the Integrated Support Center should follow), (iii) to lock and
unlock the dispensing
ability on the individual drug dispensing unit based upon a discussion with
the patient and/or his
care giver, and (iv) to lock all appropriate dispensing devices that contain a
recalled opioid and
to instruct the patient via a message on their mobile phone, tablet and/or
computer, by text
message, by email, voice messages, by twitter, and/or any other like
communication services to
go to their pharmacy to get the opioid replaced or to follow the recalling
manufacturer's
instructions.
[00051] The Integrated Support Center's support team uses metadata analysis
as well as
opioid registry information, as requested by the prescribing medical
profession, to assist them in
developing the best course of therapy based on specific queries of the
Integrated Support
Center's databases and any authorized related electronic medical records. The
Integrated
Support Center can also utilize de-identified patient data in comparison with
the individual
patient's information to identify potential medication issues (e.g., under
dosing, overdosing,
increasing tolerance, addiction and/or dependence risks, potential abuse,
etc.) to assist the
physician, on a proactive basis, to manage/better manage the patient's pain
management
needs/drug therapy.
BRIEF DESCRIPTION OF THE DRAWINGS
[00052] Advantages of embodiments of the present invention will be apparent
from the
following detailed description of the exemplary embodiments thereof, which
description should
be considered in conjunction with the accompanying drawings in which:
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[00053] FIG. 1 is an exemplary embodiment of a closed loop system to
control opioid
diversion, misuse, abuse, addiction, dependence, overdose, and deaths.
[00054] FIG. 2 is an exemplary embodiment of a closed loop opioid drug
dispensing system
controlled by an Opioid Specific App which incorporates a Drug Specific
Dispensing Algorithm.
[00055] FIG. 3 is an exemplary embodiment of the Prescription Interface
data capture
between e-prescription Prescriber and/or pharmacy programs.
[00056] FIG. 4 is an exemplary embodiment of the logic to enter the
Prescription
information in the Pharmacy Database and in the Patient Database and to
generate a Dispenser
Opening Code (not required for disposable drug dispensers) and Patient
Identification Number
and to authorize the dispensing App to dispense the medication from the
specific Drug
Dispenser. Conversely, to deny dispensing of a prescribed opioid dose from
more than one Drug
Dispenser where multiple drug dispensers containing the opioid exist. The
logic precludes
multiple dispensing/abuse via the utilization of multiple drug dispensers.
[00057] FIG. 5 is an exemplary embodiment showing specific App Modules of
an Opioid
Specific App which controls the Drug Dispenser.
[00058] FIG. 6 is an exemplary embodiment of the Biometric Authentication
setup and log
on.
[00059] FIG. 7 is an exemplary embodiment of the loading of the drug
cassette into a
reusable drug dispenser. The drug cassette is preloaded and sealed into
disposable drug
dispensers.
[00060] FIG. 8 is an exemplary embodiment of how the drug dispenser's
firmware,
database, and software will be updated/synced.
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[00061] FIG. 9 is an exemplary embodiment of data syncing between the
Patient Database
and the Opioid Specific App.
[00062] FIG. 10 is an exemplary embodiment of the Interface Database
organizational
structure and relation with the Patient Database.
[00063] FIG. 11 is an exemplary embodiment of the starting logic sequence
when the
patient accesses the Opioid Specific App and the App logic checks to ensure
the opioid is
efficacious.
[00064] FIG. 12 is an exemplary embodiment of the prescription dispensing
compliance
sequence.
[00065] FIG. 13 is an exemplary embodiment of the access and storage of
digitally captured
patient data/values.
[00066] FIG. 14 is an exemplary embodiment of the input and storage of
patient self-
assessment, self-test, and/or self-report values.
[00067] FIG. 15 is an exemplary embodiment of the information capture and
storage of
concomitant medications, tracked drug side effects, and additional clinical
trial patient
information.
[00068] FIG. 16 is an exemplary embodiment of a flow chart/decision tree
used by the
opioid specific Drug Dispensing Algorithm.
[00069] FIG. 17 is an exemplary embodiment of the support triage used by
the Integrated
Call Center to respond to drug dispenser and/or medication dispensing issues.
[00070] FIG. 18 is an exemplary embodiment of a flow chart of a standard
prescription log
in, Patient Self-Assessment, Patient Self-Test, Patient Self-Reporting,
digitally captured values
and/or information, and drug dispensing or dispensing control screens.
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[00071] FIG. 19 is an exemplary embodiment of different devices and the
types of data that
can be captured digitally by the Opioid Specific App utilizing various
application programming
interfaces (APIs).
[00072] FIG. 20 is an exemplary embodiment of the Drug Dispenser and
related Drug
Cassette docking.
[00073] FIG. 21 is an exemplary embodiment of how the Drug Dispenser can be
lengthen or
widened to accommodate larger pills and/or more drug doses or widened to
accommodate more
than one Drug Cassette.
[00074] FIG. 22 is an exemplary embodiment of other drug dispenser designs
as well as
different drug dispenser configurations.
[00075] FIG. 23 is an exemplary embodiment of different Drug Cassettes on
various
exemplary pill configurations and number of tablets of different sizes that
can be accommodated
by an individual Drug Cassette.
[00076] FIG. 24 is an exemplary embodiment of Patient dosing times versus
Patient Self-
Assessment, Patient Self-Test, Patient Self-Reported, and or digitally
reported Patient Values
Reporting Screens.
[00077] FIG. 25 is an exemplary embodiment of the Consolidated Therapy App
and various
Multi-Drug Drug Dispensers designed to accommodate more than one Drug
Cassette.
[00078] FIG. 26 is an exemplary embodiment of the Centralized IT System
utilized to
support the various drug dispensing systems.
[00079] FIG. 27 is an exemplary embodiment of an Integrated Support Center,
triage center.
[00080] FIG. 28 is an exemplary embodiment of how the Reusable Drug
Dispenser's clam
shell design is assembled for secure, tamper resistant closing and opening.
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[00081] FIG. 29 is an exemplary embodiment of the electronics schematic for
the Drug
Dispenser.
[00082] FIG. 30 is an exemplary embodiment of the placement of electronics
and
mechanical components on the outside and within the Drug Dispenser.
[00083] FIG. 31 is an exemplary embodiment, using oxycodone as an example,
of the
correlation of opioid plasma levels and pupil size.
[00084] FIG. 32 is an exemplary embodiment of a how pupil size can be used
as an opioid
overdose screen/diagnostic indicator.
[00085] FIG. 33 is an exemplary embodiment of the anatomy of eyes and the
difference in
dilation from bright light to dark light.
[00086] FIG. 34 is an exemplary embodiment showing how to detect,
authenticate, and
capture iris and pupil data to educate a dispense or do not dispense decision.
[00087] FIG. 35 is an exemplary embodiment of an algorithm used from the
captured
normalized pupil data to making a dispense or do not dispense decision.
[00088] FIG. 36 is an exemplary embodiment of the data capture screens and
sequence for a
motor skills self-test to ascertain cognitive impairment.
[00089] FIG. 37 is an exemplary embodiment of the dispense or do not
dispense Oxycodone
algorithm for the motor skills self-test.
[00090] FIG. 38 is a continuation of the exemplary embodiment of the
dispense or do not
dispense Oxycodone algorithm for the motor skills self-test depicted in Fig.
36.
[00091] FIG. 39 is an exemplary embodiment of an Oxycodone dispensing
patient interface
using a pupil scan and a motor skills self-test in combination to reduce the
number of false
positive (e.g., erroneous dispense or do not dispense decisions).
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[00092] FIG. 40 is an exemplary embodiment of the opioid dispensing
algorithm (using
oxycodone as an example) used with a pupil scan and a motor skills self-test
in a sequential order
decision logic designed to reduce the number of false positives (e.g.,
erroneous do not dispense
decisions).
[00093] FIG. 41 is an exemplary embodiment of the self-assessment and self-
reporting
screens used in sequence to reduce the number of erroneous opioid dispense or
do not dispense
decisions.
[00094] FIG. 42 is an exemplary embodiment of an algorithm that uses self-
assessment and
self-reporting responses to reduce the number of erroneous opioid dispense or
do not dispense
decisions.
DETAILED DESCRIPTION OF THE INVENTION
I. Terms and Acronyms
[00095] Terms used in this document, AKA denotes terms used
interchangeably:
[00096] Abuse (AKA Substance Abuse, Medication Abuse, Drug Abuse, Opioid
Abuse,
etc.) refers to the act or practice of improperly using medications (e.g.,
opioids, anxiolytics,
antidepressants, stimulants, etc.). It also refers to the compulsive,
excessive, and self-damaging
use of habit forming drugs or of using opioids in harmful amounts, leading to
addiction or
dependence, serious physiological injury (such as damage to kidneys, liver,
heart) and/or
psychological harm (such as dysfunctional behavior patterns, hallucinations,
memory loss), or
death.
[00097] Addiction (AKA Drug Addiction, Substance Use Disorder, Opioid
Addiction) is
defined as a chronic, relapsing disease that is characterized by compulsive
drug seeking and use,
despite harmful consequences. As an example, in the case of opioids, it refers
to the compulsive
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need for and use of an opioid or opioids, e.g., a habit-forming substance,
characterized by
tolerance and by well-defined physiological symptoms upon withdrawal; broadly:
persistent
compulsive use of a substance known by the user to be harmful.
[00098] Adverse Event (AKA: AE, Adverse Event, Adverse Experience, Adverse
Drug
Event, ADE, Adverse Drug Reaction, ADR, or Unexpected Adverse Drug Reaction,
etc.) refers
to (i) a medical occurrence temporally associated with the use of a medicinal
product, but not
necessarily causally related, (ii) any response to a drug which is noxious and
unintended, and
which occurs at doses normally used in man for the prophylaxis, diagnosis, or
therapy of disease,
or for the modifications of physiological function, (iii) an unexpected
reaction not consistent
with applicable product information or characteristics of the drug, and (iv)
the unintended effect
occurring at normal dose related to the pharmacological properties of a
medication, etc.
[00099] Allied Healthcare Professionals as used in this patent refers to
all non-physician
healthcare professionals engaged in caring for a patient inclusive of nursing,
physician assistants,
medicine, and pharmacy which may or may not have the authority to prescribe an
opioid.
[000100] API (AKA Application Program Interface) is a set of routines,
protocols, and tools
for building software applications. The API specifies how software components
should interact.
The API is the interface shared by two applications or programs that allow
both to communicate
with one another.
[000101] Beyond-use date (see Expiration Date)
[000102] Biometric Authentication (AKA Biometric Identification, Biometric
Sign On)
encompasses but is not limited to biometric technologies that digitally
capture fingerprint, palm
and full-hand scanners, voice, facial recognition systems, iris scanning
technology, pupil scans,
document readers, biometric software, and related services capable of
wireless, mobile or
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stationary use to limit access to the Patient. In this document the term also
incorporates any
system, while not biometric, that allows access via the use of a Login Name in
combination with
a Password and/or any additional security information, e.g., a computer-
generated password that
is sent by a server via email and/or text message, as well as programs
developed to allow for the
personalization of motions or movements, etc. to restrict access only to the
Patient.
[000103] Breakthrough Dose (AKA BTD, Rescue Dose) is an as needed
additional
medication dose used to control breakthrough pain (a transitory flare of pain
that occurs on a
background of relatively well controlled baseline pain, for the
treatment/management of sporadic
worsening of pain). It does not replace or delay the next routine dose.
[000104] Caregiver is defined as any individual, such as a physician,
nurse, disease
management representative, allied health professional, social worker or family
member,
guardian, or friend who assists a patient in the identification, prevention,
management, and/or
treatment of an illness or disability.
[000105] CDC (AKA Centers for Disease Control and Prevention).
[000106] Central Servers (AKA Cloud Servers, Centralized Server Structure)
refers to the
centralized computer system that stores all patient related data and
communications. It refers to
the hardware where programs are stored and databases reside to support all
patient specific
activities required to manage and control related drugs dispensing.
[000107] Cognitive Computing in this patent refers to computer systems,
most notably IBM
Watson, that rely on deep learning algorithms and neural networks to process
information by
comparing it to a teaching set of data. The more data the system is exposed
to, the more it
learns, and the more accurate it becomes over time. The neural network is a
complex "tree" of
decisions the computer can make to arrive at an answer. The programs help
collate the span of
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knowledge around a condition, for instance the patient's pain, including
patient history, journal
articles, best practices, diagnostic tools, etc., analyze that vast quantity
of information, and
provide a recommendation regarding the best course to treatment to control the
pain. Cognitive
computing can also be utilized to continually analyze metadata to compare a
patient's trended,
for example, pupil scans, to predict if a patient is in danger of overdosing.
Alternatively, it can
be used to track pupil size, early dispensing attempts, drug dispenser tamper
attempts, and pain
self-assessment scores along with other patient data to warn the prescriber
about potential opioid
dependence, addiction, abuse, and/or diversion problems. It can be used by the
Integrated
Support Center to use face recognition, via images from the patient's smart
phone, and tone
analysis to help educate the Support Center counselor regarding whether a
requested opioid drug
dispenser lock should be unlocked and a dose dispensed.
[000108] Compliance (AKA Adherence, Capacitance, Prescription Compliance,
Medication
Compliance, Drug Compliance) describes the degree to which a patient correctly
follows the
prescription's drug dosing, dispensing and storage instructions.
[000109] Consolidation App (AKA Multiunit Dispenser App) is an App designed
to
recognize other Drug Specific Apps resident on a standalone dispenser or
Interface Device and
then to consolidate the requisite digitally captured information, Patient Self-
Assessment screens
and/or Patient Self-Test screens and/or Patient Self-Reported screens into a
single interface for
the control and dispensing of multiple drugs.
[000110] Data Input Interface (AKA Data Interface, Data Input) refers to
the program
designed to interface with the applicable e-prescribing programs (e.g., ADSC
MedicsRx,
Allscripts, DAW Systems, DrFirst Rcopia, MDT Toolbox-Rx, Medtab RxCure, OA
Systems,
Practice Fusion, RxNT eRx, Spectra eRx, etc.) and/or pharmacy prescription
systems (e.g.,
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OmniCare, QS/1, PharMerica, Frameworks, etc.) and/or Electronic Prescribing
Networks (e.g.,
SureScripts - that seamlessly connects Prescribers with Pharmacies) to
streamline patient data
input and minimize or eliminate duplicate data entry requirements.
[000111] Dependence (AKA Physical Dependence) refers to the physiological
adaptation of
the body to the presence of a substance, e.g., opioids. It is defined by the
development of
withdrawal symptoms when the substance is discontinued or when the dose is
reduced abruptly
or, specifically in the case of opioids, when an antagonist (e.g., naloxone)
or an agonist-
antagonist (e.g., pentazocine) is administered. Physical dependence is a
normal and expected
aspect of certain medications and does not necessarily imply that the patient
is addicted.
[000112] Digitally Captured refers to digital Patient data captured by
diagnostic or
monitoring devices and stored and/or transmitted in a machine-readable format.
Digitally
captured information can come from multiple sources such as apps resident on a
smartphone or
computer, data captured by the drug dispenser, from RFID chips embedded in the
drug, from
selfie images, from biometric logon (e.g., pupil size), from digital
interfaces, from digitalized
diagnostic devices, and/or from digital monitors, etc. The data may be used by
the opioid
dispensing algorithm to make a dispense decision, and/or by the prescriber to
better manage the
patient, and/or by the drug's sponsor to capture clinical trial information,
and/or by the patient to
ascertain how effective the opioid is for treating and controlling their pain,
etc.
[000113] Dispensing Site (AKA Pharmacy) is defined as a pharmacy or any
other medical
facility, physician's officer, clinic, or the Patient's home where the
prescription is dispensed.
[000114] Dispensing System (AKA Standalone Dispensing System, Disposable
Dispensing
System) is comprised of the opioid, Drug Cassette containing the opioid, a
Drug Dispenser, the
Opioid Specific App which contains an Opioid Specific Dispensing Algorithm,
the Interface
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Device or Standalone Drug Dispenser where the Opioid Specific App resides, and
the Integrated
Support Center with its related Data Bases and Data Servers. The standalone
Dispensing System
is comprised of the opioid, Drug Cassette containing the opioid, a Drug
Dispenser, an Opioid
Specific App which contains an Opioid Specific Dispensing Algorithm. The
Disposable
Dispensing System is comprised of the opioid, Drug Cassette containing the
opioid (which may
be an integral part of the Drug Dispenser, a Drug Dispenser, the Opioid
Specific App which
contains an Opioid Specific Dispensing Algorithm, the Interface Device (it can
also be a
Standalone Drug Dispenser) where the Opioid Specific App resides, and the
Integrated Support
Center with its related Data Bases and Data Servers. All the Drug Dispensers
interface with and
relate to the Integrated Support Center with its related Data Bases and Data
Servers.
[000115] Diversion (AKA Opioid Diversion, Drug Diversion) is a medical and
legal concept
involving the transfer of any legally prescribed controlled substance from the
individual for
whom it was prescribed to another person for any illicit use.
[000116] Docked refers to the Drug Cassette residing in the Drug Dispensing
Unit. Docked
can also refer to a Drug Dispenser which is stored into a multiple Drug
Dispenser Dispensing
Unit.
[000117] Drug (AKA opioid, pharmaceutical, medication, medicament, OTC drug,
supplement, or herbal remedy, etc.)
[000118] Drug Cassette is either a reusable or disposable unit that
contains an opioid to be
dispensed over a defined period of time and/or days per the prescription
instructions that is
designed to dock into a Drug Dispenser or designed to be an integral part of a
Disposable Drug
Dispenser. The Drug Cassette may come either prefilled with the opioid from
the drug
manufacturer or filled by a medical professional at the pharmacy or at any
location which is
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authorized to dispense the opioid. The Drug Cassette may be an independent
device designed to
dock into a Drug Dispensing Unit or may be an integrated Drug Cassette in a
disposable Drug
Dispenser.
[000119] Drug Dispenser (AKA Dispensing Device, Opioid Drug Dispenser,
Standalone
Dispenser, Dispensing Unit, Disposable Drug Dispenser, Disposable Dispenser,
etc.) refers to the
Drug Dispensing Unit with a Docked or Integrated Drug Cassette whose
dispensing is controlled
by an Opioid Specific App or a Standalone Drug Dispenser with a resident
Opioid Specific App
or a drug dispensing program that controls dose drug dispensing by the
dispenser.
[000120] Drug Dispensing Unit (AKA Reusable Drug Dispenser, Drug Dispensing
Device,
Drug Delivery Device, Standalone Drug Delivery Device, Standalone Drug
Dispenser,
Disposable Drug Dispenser, Multiple Drug Dispenser) is the device where the
Drug Cassette is
resident in the Dispensing Unit and whose dispensing mechanism (lock, unlock,
and dispensing)
are activated by Firmware controlled by a Opioid Specific App and/or Drug
Specific Apps or the
resident software logic contained in the Standalone Drug Dispenser.
[000121] Drug Dispensing Software refers to dispensing software resident on
an interface
device or Standalone Drug Dispenser that: 1) requires Biometric
Authentication, and 2) controls
dose dispensing by a Drug Dispenser/Drug Dispensing Unit.
[000122] Drug Specific Dispensing Algorithm refers to the decision tree
based algorithm
specifically developed for each opioid and opioid formulation to ascertain if
the drug dose should
or should not be dispensed.
[000123] Electronic Medical Record (AKA EMIR, Electronic Health Record,
EHR, Patient
Medical Record, PMR, etc.) refers to the systematized collection of patient
and population
electronically-stored health information in a digital format. These records
can be shared across
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different health care settings. The centralized Electronic Medical Record for
each Patient
maintained by the Integrated Support Center on its Centralized Servers is
designed to store all
captured opioid/medication dispensing information and all interactions between
the Integrated
Support Center representative and medical personnel and the Patient and/or
caregivers. The
information is made available to authorized providers in keeping with HIPPA
guidelines and
general requirements for protecting and sharing health information. It
captures and stores all the
information that is captured by the App as prescribed by the physician or
dictated by clinical trial
requirements, as required.
[000124] Encryption (AKA Encrypted, Encrypted communications) is the most
effective way
to achieve data security. Access requires a secret key or password that
enables decryption.
Unencrypted data is called plain text; encrypted data is referred to as cipher
text. Encryption as
used in this patent, by definition, is encryption which is designed to meet
all HIPPA security
standards or general requirements for protecting health information.
[000125] Expiration Date (AKA Beyond-Use Dates, Drug Expiration Date,
Expiration/Beyond-Use Date) refers to the date after which a medication should
not be taken
(should not be dispensed) because an expected decline in quality or
effectiveness. For this
patent, Expiration Date is the shorter of the manufacturer assigned expiration
date and the
pharmacy assigned "Beyond-use date". The "Beyond-Use Date" is the date placed
on a
prescription by a pharmacy noting when that prescription should no longer be
used. It will often
say "discard after ..." or "do not use after ...".
[000126] Firmware is embedded systems software contained in the Drug
Dispenser's
memory to provide operating systems control, sensor information capture
Oalerts, and handshake
with the Interface Device.
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[000127] Handshake (AKA Digital Handshake) refers to an exchange of signals
between
devices ensuring synchronization whenever a connection, as with another
device, is initially
established.
[000128] Integrated Support Center (AKA Call Center, Patient Support
Center, Physician
Support Center, Prescriber Support Center, etc.) refers to an Integrated
Support Center designed
to: (i) provide patient support related to the Drug Dispenser, Opioid Specific
App, alerts, locked
dispenser screens, the opioid, or health related questions. It can triage
calls from dispenser and
App technical support to the appropriate opioid counselor, to the prescriber,
to the patient's
physician, and/or any contracted disease management services; and/or (ii)
assist prescribers in
optimizing opioid therapy for a patient, and (iii) answer any business
questions (e.g., customer
inquiries regarding invoices, billing, orders, pricing, shipments, etc.).
[000129] Interface Device refers to the smartphone, tablet, computer, or
standalone drug
dispenser, etc. with Internet communications capabilities or like
communications capabilities
where the Opioid Specific App resides which allows communications with the
Integrated
Support Center Servers (Central Computers).
[000130] Locked indicates the drug cannot be dispensed by the Dispensing
Device until the
Opioid Specific App or the standalone device's dispensing software unlocks the
Dispensing unit
and allows it to dispense the medication.
[000131] Long Acting Medications (AKA Sustained Release, SR, Controlled
Release, CR,
Extended Release, ER) are slowly effective medications after initial dosage,
but maintaining its
effects over a long period of time, being slowly absorbed and persisting in
the tissues before
being excreted. These can come in various forms, but by reference in this
patent, refer to oral or
transdermal formulations.
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[000132] Long Acting Opioids (AKA Sustained Release, SR, Controlled
Release, CR or
Extended Release, ER). These can come in oral or transdermal formulations.
[000133] Medication (AKA Drug, Pharmaceutical) refers to a substance used
for medical
treatment, especially a medicine or legal or illegal drugs, OTC medications,
vitamins, dietary
supplements, herbal medicines, and/or recreational drugs, etc.
[000134] Metadata Analysis (AKA Structural Metadata Analysis, Descriptive
Metadata
Analysis, Big Data, Big Data Analytics) as used herein refers to the use of
the organization of
patient data to enable analysis of both individual and patient population data
to ascertain how to
best manage opioid therapy on an opioid by opioid and patient by patient
basis. By reference, it
incorporates the use of cognitive computing to ascertain how to best treat an
individual patient's
pain based upon the patient's own information as well as that of de-identified
patient records, a
patient's facial scan, and/or the patient's tone.
[000135] Opioids (AKA Opiates, Short Acting Opioid, Long Acting Opioid)
refers to all
agonists and antagonists with morphine-like activity, and also the naturally
occurring and
synthetic opioid peptides. This definition also includes all drug combinations
which include at
least one opioid in the drug combination. Examples of opioids are:
buprenorphine, codeine,
fentanyl, hydrocodone, hydromorphone, methadone, morphine, oxymorphone,
oxycodone,
tapentadol, and tramadol, etc.
[000136] Opioid Specific App (AKA Opioid Specific App, Patient Tailored
Opioid Specific
App, Opioid Specific and Patient Tailored App, Medication Specific App, App)
refers to an app
that requires Biometric Authentication prior to a Patient being able to
respond to Patient Self-
Assessment screens and/or Patient Self-Tests screens and/or Patient Self-
Report screens which
are used by the App's Drug Specific Dispensing Algorithm to decide whether or
not to signal the
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Dispensing Device to dispense the opioid or to indicate to the patient and/or
Integrated Support
Center why the opioid is not being dispensed.
[000137] Opioid titration has traditionally been referred to as adjusting
the dosage of an
opioid. It requires regular assessment of the patient's pain, when and why it
occurs as well as the
amount of medication used in the previous 24 to 72-hour period.
[000138] Opioid rotation is switching one opioid for another. It is
required for patients with
inadequate pain relief and / or intolerable opioid related toxicities or
adverse effects.
[000139] Opioid withdrawal occurs when an opioid is discontinued abruptly.
Withdrawal
symptoms last for a few days and are generally the opposite of symptoms
exhibited when the
opioid was started.
[000140] Opioid naive patient refers to an individual who has either never
had an opioid or
who has not received repeated opioid dosing for a 2 to 3-week period.
[000141] Opioid tolerance is a state of adaptation in which exposure to an
opioid induces
changes that result in a diminution of one or more of the drug's effect over
time. It is a known
pharmacologic effect of opioids. Tolerance to the analgesic effects of opioids
is relatively
uncommon.
[000142] Oral Patient Controlled Analgesia (AKA OPCA) is any method of
allowing a
person in pain to administer their own pain relief Historically, this has been
limited to infusion
using an infusion pump that is programmable by the prescriber. If it is
programmed and
functioning as intended, the machine is unlikely to deliver an overdose of
medication. The
embodiment of the invention expands the application to oral medications. The
prescriber
indicates the limitations put on the patient regarding the dispensing of his
oral opioid.
Dispensing may be controlled to: 1) a specified number of pills (doses) during
a defined time
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interval; or 2) the number of pills that may be prescribed during a defined
time interval with the
limitation that individual doses not to be dispensed more frequently than a
given timeframe
between each dose, e.g., minimum of 20 minutes between doses, etc.
[000143] Patient refers to the individual that is prescribed and is taking
an opioid and/or
medications.
[000144] Patient Database refers to all the patient data stored in the
Central Servers. The data
may be stored in one of more databases and on one or more servers which are
collectively
referred to as the Patient Database.
[000145] Patient Reported Outcomes (AKA PRO) is a method or questionnaire
used in a
clinical trial where the responses are collected directly from the patient.
Collection may be via
automatic digital capture, or via patient inputted self-assessment, self-test,
or self-report
physiological, psychological, lifestyle, concomitant medications, or
environmental
information/data.
[000146] Patient Self-Assessment (AKA Patient-Reported Outcome, PRO) covers
a whole
range of potential types of measurement resulting from a (i) patient
responding to a question, (ii)
a self-administered test, (iii) a self-report input which is digitally
captured, and/or (iv) digital
diaries whose information can be quantified for utilization by the Drug
Specific Dispensing
Algorithm and/or for utilization by the Prescriber for better Patient
management and/or by a drug
sponsor for clinical trial information reporting. Each self-assessment scale
or question or diary
input measures a single underlying characteristic(s). Examples include, but
are not limited to
responding/reporting, (i) the level of pain (e.g., responding to the Mosby
Pain Index, Wong-
Baker Facial Grimace Scale, etc.), (ii) an activity tolerance scale, (iii) a
quality of life scale, (iv)
a discomfort scale, (v) a physiologic value (e.g., blood pressure, heart rate,
eye dilation, balance,
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gait, weight, food consumption), (vi) stress, (vii) blood oxygen saturation,
Sp02, etc. The
definition may include, but is not limited to, certain patient self-
administered tests (also refer to
as Patient Self-Test) or self-reported observations (also referred to Patient
Self-Report).
[000147]
Patient Self-Test refers to any test which is responded to by the patient and
digitally
captured to allow the Drug Dispensing Algorithm to make a drug dispensing
decision.
Examples, with specific applicability to opioids, include but are not limited
to: (i) a fine typing
test to ascertain cognition (speed and accuracy of movement); (ii) a walking
test to ascertain
balance and/or gait; (iii) voice test to ascertain the clarity and flow of
speech; (iv) memory test to
gauge cognitive status, motor functioning, attention/working memory,
processing speed, and
executive functioning, as well as learning and memory, (v) a manual acuity
test to ascertain
alertness and cognition, (vi) data entry test to ascertain cognition, etc.
This information can be
quantified for utilization by the Drug Specific Dispensing Algorithm and/or
for utilization by the
Prescriber for better Patient management and/or by the drug sponsor for drug
clinical trials data
capture.
[000148]
Patient Self-Report is defined as any response made by the patient which is
based
upon his/her action, observation or best recollection. Examples include, but
are not limited to, (i)
OTC, herbal, or other medications taken over a prespecified period of time (as
an example, in the
case of opioids, this may be a question that deals with medications taken
since the last opioid
dose which would result in a medication or drug-drug interaction with the
opioid), (ii) how the
patient's stool composition appears (e.g., on the Bristol Stool Index), (iii)
the last time the patient
had a bowel movement, (iv) digital diaries (e.g., iPhone Health App, Samsung's
S Health,
disease specific diaries), etc. This information can be quantified for
utilization by the Drug
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Specific Dispensing Algorithm and/or for utilization by the Prescriber for
better Patient
management, and/or by the drug's sponsor for use in clinical trials data
reporting, etc.
[000149] Patient Specific Opioid Specific App (AKA Opioid Specific App)
refers to an
Opioid Specific App used to control opioid dose dispensing from a drug
dispenser. The is
automatically prescribed by the physician when prescribing the related opioid.
The prescriber
can customize the App to the individual patient by requesting certain side
effect information be
tracked that is not required by the Drug Specific Dispensing Algorithm to make
a dispensing
decision. The Opioid Specific Patient Tailored App can also be programmed to
capture patient
management and clinical trial information/data not required to make an opioid
dispensing
decision.
[000150] Persistence (AKA Prescription Persistence, Medication Persistence)
refers to the act
of continuing the treatment for the prescribed duration. It may be defined as
"the duration of time
from initiation to discontinuation of therapy." No overarching term combines
these two distinct
constructs.
[000151] Pharmacodynamics is the study of the biochemical and physiological
effects of
drugs on the body or on microorganisms or parasites within or on the body and
the mechanisms
of drug action and the relationship between drug concentration and effect.
[000152] Pharmacokinetics is the study of the bodily absorption,
distribution, metabolism,
and excretion of drugs.
[000153] Physician's Office is broadly defined as a medical facility, room,
or rooms in which
the physician and staff provide patient care; a location in which one or more
medical doctors
receive and treat patients. Examples include sole practitioner office,
physician group practice
offices, hospital clinics, out-patient ambulatory care centers, telehealth
location, etc.
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[000154] Polypharmacy is the practice of administering or using multiple
medications
especially concurrently (as in the treatment of a single disease or of several
coexisting
conditions).
[000155] Prescriber is defined as any healthcare professional authorized by
an individual
country or state to write a prescription for a drug. Examples include
physicians, physician
assistants, nurse practitioners, nurses, pharmacists, etc.
[000156] Prescription (AKA ePrescription, Paper Prescription, Manually Entered
Prescription, Digital Prescription, Drug Prescription, Medication
Prescription) is an instruction
electronically entered or manually written by a medical practitioner that
authorizes a patient to be
provided a medicine or treatment.
[000157] Prescription Expiration Date is defined as the earlier of the drug
expiration date or
the prescription expiration date.
[000158] Recall refers to an opioid recall issued by the manufacturer or a
regulatory agency
indicating that a particular opioid batch or drug should not be taken.
[000159] Routines (AKA Software Program, Software Routines, Subroutine,
Procedure,
Function, Method, Subprogram) is a portion of software code within a larger
program that
performs a specific task and is relatively independent of the remaining code.
[000160] Serial Number (AKA Serial No., SN, S/N, Identification Number,
Tracking
Number, Identifier, etc.) is a unique number used for identification,
tracking, and/or inventory
purposes.
[000161] Short Acting Medications (AKA Immediate Release, IR) are quickly
effective
opioids that require regular repeated doses for long-term treatment. They are
rapidly absorbed,
distributed in the body, and excreted.
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[000162] Short Acting Opioids are immediate release (IR) opioids.
[000163] Steady State is when the rate of opioid (drug) availability and
elimination equal one
another.
[000164] Tamper Resistant refers to a design: 1) that precludes the drug
dispenser from being
opened without destroying it, 2) that makes it difficult to change, open, or
remove the opioid
cassette from the drug dispenser except for authorized users, or 3) that
results in damaging the
drug dispenser when an unauthorized person attempts to open the drug
dispenser.
[000165] Tethered Drug Dispenser is a Drug Dispenser that utilizes the
Interface Device's
capabilities to offer functionality and ease of use that would not otherwise
be possible in a
Standalone Drug Dispenser with the same outside dimensions, the same size.
[000166] Titration has traditionally been referred to as adjusting the
dosage until a desired
outcome is reached. Examples include opioids, dopamine, and nitroglycerine.
Titration requires
regular assessment of the patient's symptoms/values over a defined time
period.
[000167] Titration Cassette (AKA Titration Dispenser, Opioid Titration
Unit) refers to a
Drug Cassette that is configured with one or more opioids for a specified
period of time to
ascertain the right dose and dosing schedule for a single opioid or a
combination of opioids.
[000168] Tolerance is a pharmacology concept where a subject's reaction to
a specific opioid
and opioid concentration is reduced following repeated use, requiring an
increase in
concentration to achieve the desired effect. It is a state of adaptation in
which exposure to an
opioid induces changes that result in a diminution of opioid's effect over
time.
[000169] Total Daily Dose (TDD) is the 24-hour total of an opioid that is
taken for regular
and breakthrough doses.
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[000170] Withdrawal is the group of symptoms that occur upon the abrupt
discontinuation or
decrease in intake of an opioid. To experience the symptoms of withdrawal, the
patient must
have first developed a physical or mental dependence. Withdrawal symptoms
generally last for a
few days.
II. List of Opioids, Opioids Mechanisms of Action, and Level of Pain the
Invention in its
Various Embodiments is Applicable To
[000171] The invention and its various embodiments can enable the
Prescriber to better
manage and personalize a patient's opioids drug therapy. The invention can
assist the Prescriber
in personalizing a patient's opioid therapy to include: (i) establishing the
lowest effective opioid
dose, (ii) on an ongoing, real-time basis, monitoring the ability of the
opioid or opioids to
manage the patient's pain, symptoms and/or condition, (iii) adjusting the
prescribed dosage if the
patient develops opioid tolerance sufficient to require an increased dose,
(iv) facilitating the
management of the opioid to better manage drug withdrawal, (v) decreasing or
precluding opioid
overdose, (vi) precluding opioid abuse or misuse by restricting dispensing to
the prescribed
dosing interval, (vii) improving opioid drug safety by the utilization of
Patient Self-Tests to
ascertain if the patient is being over or under medicated, (viii) decreasing
opioid mediated side
effects through the utilization of Patient Self-Assessment, (ix) avoiding
unnecessary opioid
medical professional interventions/office visits, related emergency room
visits, and/or deaths by
guarding against drug-drug adverse events, and (x) ensuring proper prescribing
and prescription
compliance through real time patient data capture, control of opioid access by
the patient, and
Prescriber feedback. By improving each opioid's safety profile, the invention
improves the
patient's quality of care, ensures the continued efficacy of the opioid for
each individual patient,
improves the patient's quality of life by ensuring proper prescribing, and
increases prescription
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compliance and persistence - thereby decreasing the number of opioid related
medical
interventions, physician visits, ER visits, and hospitalizations - thereby
decreasing the total cost
of patient care ¨ and thereby decreasing the number of opioid overdose deaths.
It also decreases
healthcare costs by decreasing opioid diversion which leads to prescription
opioid addiction,
overdoses, misuse and abuse and their related healthcare costs.
[000172] Table 1, beginning on the next page, lists oral opioids. The
listed approved drugs
are encompassed in the embodiment of the invention by reference and can
benefit from an
improved opioid safety profile. The Invention mitigates prescription risk for
the drug
manufacturer and Prescriber as it shifts the responsibility of prescription
compliance to the
patient. The listing for each drug includes, by definition, each opioid's
respective indication(s),
strength, dosage form, route of administration, side-effect profile, drug
interactions, mechanisms
of action, manufacturer, etc.).
[000173] In addition to Table 1, the embodiment incorporates by reference
all marketed and
in development oral opioids listed in: (i) Goodman & Gilman's, The
Pharmacological Basis of
Therapeutics (12th Ed) (Goodman et al. eds) (McGraw-Hill) (2011); (ii) 2015
Physician's Desk
Reference; (iii) CortellisTM Competitive Intelligence by Thomson Reuters; (iv)
Adis R&D;
and/or (v) Pharmaprojects by Citeline. The listing for each drug includes, by
definition, each
opioid's respective indication(s), strength, dosage form, route of
administration, side effect
profile, drug interactions, mechanisms of action, manufacturer, etc.
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fb
0
.....
.
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g
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;
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2
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,...... ..... .....
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=
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st; o
...............................................................................
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o
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u EP ........ cr,
.
...............................................................................
..................... -0
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,
CA 03014319 2018-08-10
WO 2017/139761
PCT/US2017/017665
[000174] Each opioid's side effects are listed in the opioid's package
insert. Each side effect
can be tracked using the respective Patient Self-Assessment, Patient Self-
Test, and/or Patient
Self-Report screens or digitally captured diagnostic, monitoring, or patient
maintained
information. Table 2 is an exemplary listing of side effects that can be
tracked by the prescriber
using a selection on the prescription or other input media that enables a data
capture screen to be
incorporated into the Opioid Specific App. The information may or may not be
incorporated into
the Patient Specific Dispensing Algorithm. The Opioid Specific App can be
customized to
request the information each time or at specified intervals. This allows the
Patient Opioid
Specific App to be tailored to each patient to assist in patient management.
The drug specific
side effects for each opioid are listed in each opioid's package insert and
are hereby incorporated
by reference.
Table 2: Sample Opioid Side Effects
w
c o' 14,., EL .2 TD
M C Cll
'17 0 CU C
C1)
c 7 -C C a
¨ -a - 0 0. -0 Et
t 8 -5 E `,8' V. 7' 2
0 0 -C 0 ¨ c g a,
>.- -a 5 -a >. Q. c o.
Opioid Side Effects
Abdominal or Stomach Pain X X X
Abdominal or Stomach Pain or Discomfort X
Abdominal Pain X ..
Abnormal Dreams X : .. X ; .. :
: X :
Abnormal Gait ; X : : :
=
................................................................ . .. .
:
Abnormal Vision XAbsent, Missed, Or Irregular Menstrual Periods
Accidental Injury X
;1,---- õ :
. . .
Acid or Sour Stomach Xi Xi i
Agitation XI X )
. . .
Amnesia X
. . .
Anorexia X I
Anxiety X 1 : : =
: : X
Back Pain X X : :
: X X
Bad, Unusual or Unpleasant (After) Taste i XBad, Unusual,
Or Unpleasant (After) Taste
+ .. + +
Being Forgetful X ..........................................
Being Forgetful or Confused X .. :
......................................................... 4 .. =:, =:,
=:,
Belching
......_,.......................................................................
...............................................................................
...............................................................................
............................................_ ...... J _x _Lx
Biaci,Tarrytoois ---------------------------------------- 1 ---- I I I
X
Bladder Pain X .............................................. : .. X
õ . . .
,
Bleeding After Defecation ,; X
Blistering, Crusting, Irritation, Itching, Or Reddening of the Skin X
Bloating or Swelling of the Face, Arms, Hands, Lower Legs, Or Feet X 1 X
X
. . .
Bloody or Cloudy Urine X ----------------------------------- : -- : =
: : X
i . . .
Bloody, Black, Or Tarry Stools ,; X . .
.
Blue Lips and Fingernails X
Bluish Lips or Skin õt4Eõ ____________________________ _ t __ x :
CA 03014319 2018-08-10
WO 2017/139761 PCT/US2017/017665
w
++ CU
CI c 61
3 _c c = -
===(/) cf. 0 ¨,.. .0
c 0 L .. .0
'-
.-
C
0 C
M Cld
E
i-
>== -a 0 -a . D. c a
Opioid Side Effects cu
m
Blurred Vision IXt XI t
XIX: :XI X
Body Aches or Pain ; IX; t ; -
- :XI -- z
Bulging Soft Spot On the Head of an Infant
----- --t ' t 1 --t
Burning, Crawling, Itching, Numbness, Prickling, "Pins and Needles", Or
Tingling Feelings X
: .........
Change in Consciousness X X
.
Change in Taste X
Change in The Ability to See Colors, Especially Blue or Yellow X
Change in Vision I X :
..,, , ..,, : --
..,, -- = -- .:,
Change in Walking and Balance I I I I
I I X
Change or Problem with Discharge of Semen
Changes in Behavior I I I
I)0 IXI
Changes in The Patterns and Rhythms of Speech I I I I x
-------- -I ----,,- -- : -- ,,---- -: -- i- -- -- '¨
Changes in Vision I I I I --
I -- i x
Chest Pain I X I I I --
I -- i -- i x
'¨
Chest Pain or Discomfort I= XIXI
IXI)(i i
: --`--- i ----`-- i
i
Chills IXIXI ............................................... IXIXi Xi
Clumsiness t I I I X
I I I I
, , = = ,
Clumsiness or Unsteadiness t ; t ;
.. I iXiX
Cold and Clammy Skin ; IX; t t) -
- I -- z
Cold Sweats X : X ..
Cold, Clammy Skin X X
. :..
:
. , ,
Confusion X X X
X: :XX
. . = .. .
Confusion as to Time, Place, Or Person I I
I
Constipation I I : X
i I
Constricted Pupil (Black Part of the Eye) I I X
Constricted, Pinpoint, Or Small Pupils (Black Part of the Eye) IXI I
IXIXI i
Continuing Ringing or Buzzing or Other Unexplained Noise in The Ears I
I I I X
Convulsions (I I I)0
IXiX
Cough ....................................................... IXIXI
IXIXiXIX
,,---- 1 -----1- :
,,---- -: :- -- '¨
Cough Increased IXI
- -' - -; -- -
-- : -- =
Cough or Hoarseness I I ; I
: i>( X
........................................................ ..õ.. :,= õ, -
-- ..õ.. , -- . -- -- ,,,
Coughing That Sometimes Produces a Pink Frothy Sputum ; I x
Cracked, Dry, Scaly Skin t .............................. ; I ;
IXi :
Cramps
Crying t ; t ; X
----- --t ' t 1 --t
Decrease in Consciousness : X : L
:-
Decrease in The Frequency of Urination X X
. . :- : --
Decrease in Urine Volume X X X
:- . . =
:.. :
Decreased Appetite X : X
i I
Decreased Awareness or Responsiveness ,
X : X :X X: :X
.,. , .,. : ..
.,. = _.:,
Decreased Frequency of Urination I I I I
I I X
Decreased Interest in Sexual Intercourse I I I I
X
Decreased Urination I I I
I)OXI I
Decreased Urine I I I i
i X
-------- -I, -----,- -- : -- ,,---- i -- :- -- -- '¨
Decreased Weight ; I I I
I x
Deep or Fast Breathing with Dizziness I I I X
........................................................ ,,---- -I -----,-
: ,,---- -: :- -- '¨
Dehydration I X
- ..õ.. :,= õ,õ .=
- -:
- -' - -; -- -
-- : -- =
Delusions
Delusions of Persecution, Mistrust, Suspiciousness, Or Combativeness t
I I X I I I
Dementia
Depersonalization ; X
Depression X; X X;
: = +
Diarrhea X : :X X:
:X :X
. . . =
. -- , --
49
CA 03014319 2018-08-10
WO 2017/139761 PCT/US2017/017665
al
CO C CU
4.= 0 al c
c ul . et 0 T.,
...c¨
_c =-= cs
TS 41 a 0 -0 _ "
'w a C E " m,..,
C =:e. 0
4., c C
8 2 EL 2 E
>. 'a e, "0 >. ta. c a
0) m
Opioid Side Effects 0
1 2 1 µ2 _t u_ co
...............................................................................
...............................................................................
........................)¨r....).......r.¨. ., ..,.............
Difficult or Labored Breathing i)(;) i X i
: X
, , +
Difficult or Troubled Breathing i I I i
i X
Difficult, Burning, Or Painful Urination i I X I I
i x i
Difficult, Fast, Noisy Breathing, Sometimes with Wheezing I i x
-------- -I ---i- : -i---- i :- -- '¨
Difficulty Having a Bowel Movement (Stool) i IXI IXIXi
iX X
Difficulty in Passing Urine (Dribbling) ................ IXi I iXIXi
i
-i---- ,== ---i- : -
i---- i :- -- '¨
Difficulty with Breathing i I i I
i i x i
Difficulty with Moving i ................................. i i iXi
i XiX
Difficulty with Sleeping i i i i x
Difficulty with Swallowing iXt i iXiXi
.. i I
Difficulty with Thinking or Concentrating i i i i X
Difficulty with Walking L ' X
t
t :
Discouragement :- X X i i
X . . .
Disorientation X
. . t =
Disturbed Color Perception X l .. i
Dizziness I X .... X I i
)C X
Dizziness, Faintness, Or Lightheadedness When Getting Up Suddenly from A Lying
or Sitting Position 1)0XL 1Xi 1 X
Double Vision I I i
IXIXi i
i -i= i -i=
% ' :
Drowsiness I I ixI
i Xi X
Drowsiness to Profound Coma i I i I
i x
Dry Mouth .............................................. IXIXI iXIXi
iX
...... , õ. i
...... .: . -- ....
, = -.. = -
, . :
Dry Skin i x
Dyspepsia .............................................. I X
-i---- -I ---i- : -
i---- ii :- -- '¨
Dysphagia i X
Dysphoria .............................................. I X
Dyspnea ;XI
Dysuria i X
Ear Congestion X '
t = .. .
Edema X = ..
Emotional Lability X . t ..
=:- .
Eructation X
. . t =
Euphoria X
Excess Air or Gas in The Stomach or Intestines i ...... iXIXi
i
i -i= i -i=
% ' :
Excessive Muscle Tone i I .. i i
i i X
Exfoliative Dermatitis I X
, -i= .. , .. -i=
i ' :
Extra Heartbeats I i I i x
-------- i ---ti- : -i---- ii :- -- '¨
Extreme Drowsiness I X
= -.='=-= =
-1.-. = : =
Extremely Shallow or Slow Breathing i i i i
i i iX
Face Is Warm or Hot to Touch
Facial Edema
Fainting ;XI i I i
i iXI
% = % = %
= = =
False or Unusual Sense of Well-Being i i i
iXiXi i I
Fast or Irregular Heartbeat i i i i
i X
Fast, Pounding, Or Irregular Heartbeat or Pulse L X '
t
t : t
Fast, Pounding, Racing, Or Irregular Heartbeat or Pulse X
=:- . .
. :
Fast, Weak Pulse X X
Fear or Nervousness X X
= : =
=
Feeling Drunk i i = X i
=
Feeling Faint, Dizzy, Or Lightheaded i I .. i i
i i X
Feeling Jittery ixi i = ,
.. = , = , , ,
Feeling of Constant Movement of Self or Surroundings i I ixIxi
iX
Feeling of Warmth I I i
IXIXi i
: -,, : -.=
, 4 i ,
Feeling of Warmth or Heat I X I I i I
i i X X
CA 03014319 2018-08-10
WO 2017/139761
PCT/US2017/017665
a+
4.. ty
cts c cu
..I ow C
0.1
C 1./1
0 0 m , .............................................................. _0 0
0.
3 E 0 -"t1¨ 8
E ,.., ,-- E 8 2 t c
. o ¨ o c a, al
,..) a=
,_ E 0J .1... "
>== 1:I 0 10 >0. C C.
X >== ,.. >.x 0 al 0
Opioid Side Effects 0
2 z 2 0 i¨ u- co
Feeling Sad or Empty ------------------------------------- , -- L L X
i X i X l
, = i
Fever X X X ..... iX Xi
i
Fever or Chills i
i X I X
Flatulence ^ X
Floating Feeling
t-----+----4-----4-----
Flushing or Redness of the Skin, Especially On the Face and Neck -- X :
L i lX1X
Frequent Urge to Urinate X --
Full Feeling X
,
Full or Bloated Feeling .......................................... i X
=
Gastritis X ......... i
... .....................................................................
Gastroesophagea I Reflux Disease i X ----- i --
Gastrointestinal Disorder l X
; -- ; -- .------:-
General Feeling of Discomfort or Illness i i
---,-- + ... ' ..
= - :
i
Hallucination i X l X
Halos Around Lights X .........................................
+
Headache i X X
XXXX X
Hearing Loss --------------------------------------------------- l X
;
Heart Stops l X
Heartburn i x X l X
=
i i : ¨t
Heartburn or Indigestion . -- i -- i
X
, , 4. .;
Hematuria i X
-, .................................................................... -:==
+
Hiccups i X
-i-
Hives or Welts X
Hives, Itching, Or Skin Rash i X -- i -- l
X i
.
Hoarseness ....................................................... _L X
Holding False Beliefs That Cannot Be Changed by Fact
Hyperkinesia ------------------------------------------ i -- X
, ____________________________________________________________ , -- , ,,, :
= :
;
Hyperventilation ................................................. i X
=
Hypoesthesia X ......... i
Hypotonic i X
Impotence J X
ii- i ----------------
Inability to Have or Keep an Erection l X _________________________ i
Incidence Not Known i X -- EXL -- [XL
L
Incidence Not Known i X .. X Xi
1
,
Increased Appetite X X .. i
1
Increased Blood Pressure
.r. ....................................................... . ..
= i :
i
Increased Sensitivity of the Eyes to Light X ----------------
+ + + ----------------------------------------------------------------- 4 -- 4
Increased Sweating : x X Xi
i
¨I¨ i i = +
Increased Thirst i X ....... X
+........ :... .. i.
z.... =
:- ---,
Indigestion i 1 ----- iX1)0
i 1
---- +
Insomnia i X
-i-
Irregular Heartbeat X
t ................................................................ t .. t t
Irregular, Fast or Slow, Or Shallow Breathing i X -- z i
. - -- . :
Irregular, Fast, Slow, Or Shallow Breathing i X, i _ L
L : X -
Irregular, Slow, Or Shallow Breathing
! ------------------------------------------------------------ i -- l X
: - :
t
Irritability X i X
-------------------------------------------------------------- i i =
i
Irritability or Restlessness l i X
\ + +
Irritation i ....... X
1-
Irritation, Pain, Or Sores at The Site of Application X
t ................................................................ t .. t t
Itching Skin i X -- i z
i X
. .i. ..
i.
Joint Pain, Stiffness, Or Swelling
,IXLXLXi
Lack of Appetite ' - i X 1
i
õ
Lack or Loss of Strength ------------------------------- i ----- ' i i
X i x
51
CA 03014319 2018-08-10
WO 2017/139761 PCT/US2017/017665
al
0:1 C CU
4.= 0 pj c
=¨
c v1 et. 0 T.,
..c
c 0 1... _c =-=
cs
., TS 0=1 a 0. "C _ "
''. CI C E " M >. o ,..,
C 14 0
4., = C
8 2 el E c co cu
L_ 6- tu ..... ,-
>. -c3 o) -0 ). ta. c a
(7, 0, m
Opioid Side Effects 0 1 2 1 µ
gt u_ co
Large, Hive-Like Swelling On the Face, Eyelids, Lips, Tongue, Throat, Hands,
Legs, Feet, Or Sex Organs 1 1 i X
Less Common i i X X i
Less Common or Rare X
Lethargy i i X
-------- i ---t, : --
i---- -: t -- '¨
Lightheadedness Xi i i
lX
, --`--- i ----`-- i
i
Lightheadedness, Dizziness, Or Fainting i x x
........................................................ ,,---- ,: ---,,
: ,,---- -: i- -- '----
Loss in Sexual Ability, Desire, Drive, Or Performance i i C
i --`--- i ----`-- i
i
Loss of Appetite tXi ....................................... t iXt i
iX
Loss of Balance i i t X
Loss of Consciousness ....................................... tXtXt
Loss of Interest or Pleasure i i tXiXi
i)
Loss of Taste = X
Loss of Vision X
Loss of Voice X i X l
. . . :
Low Blood Pressure or Pulse
t . . . ..
Low Body Temperature X i
l
i --= , --=
, -i= :
Lower Back or Side Pain i )(i lXiX
X
.,-. : .,-. = ..:,
Lymphadenopathy i x
,
= - . = .. = -
. = = - + =
Malaise i ) .......
Mental Depression i i i X
Migraine X
'¨
Mood Changes i i i i
i X
Mood or Mental Changes __________________________________ i i X
........................................................ --i----- Ji ----
-i- : --i----- t i- -- '----
Muscle Aches i i Ci iXi
Muscle Cramps or Spasms _____________________________
Muscle Pain or Cramps t) i i i
iX
Muscle Pain or Stiffness t i t iXt
i Xi
Muscle Spasms X
t X
t t ..
Muscle Stiffness i X
..
. . . :
Muscle Stiffness or Tightness X
Muscle Tension or Tightness i l X
Muscle Twitching or Jerking i X i i
X
.,-. . - = .= =
Muscle Weakness i .. i X
: + : + :
-i= :
Nasal Congestion X
.,-. : .,-. :
.,-. . - = .,
Nausea i)0 0 iXi X
i--= , --= ,
- + :
Nausea or Vomiting X Xi lX
-------- 1 ----i- : -
-i---- t t -- '¨
Nervousness X X X i i
X
, --`--- i ----`-- i
i
Night Blindness i i C
........................................................ --i---- i ----i-
: --i---- t t -- '¨
Nightmares or Unusually Vivid Dreams ___________________ i i i x
-,.
No Blood Pressure or Pulse t ............................ i t i
tXi i
No Muscle Tone or Movement tXX; (i
= -it- t ---t-- t - -: 4
k k : =
'
No Pulse or Blood Pressure i i t iXt
Noisy Breathing i i t X
Not Breathing L = X X ..
L
Numbness of The Feet, Hands, And Around the Mouth X
-:- . . .
=
Numbness or Tingling in The Hands, Feet, Or Lips i i X
Over Bright Appearance of Lights X
t , , =
t ,
Overactive Reflexes i X i
l
Pain in The Arms or Legs i .. i X
..,-. .. ,
Pain in The Joints i 0 i
iX
: -,== : --
,== , 4 : -,
Painful or Difficult Urination i i i i
X X
..,-. , ..,-. :
..,-. . ....
Painful Urination i iXCi
i
: --,== : --
,== , 4 : -,
Pale or Blue Lips, Fingernails, Or Skin X XXiXl
x
52
CA 03014319 2018-08-10
WO 2017/139761 PCT/US2017/017665
al
CO C CU
4.= 0 a c
c ul . et 0 ¨
...c¨
_c 0 cs
= .......................................................... , ............ TS
41 a 0 -0 _ "
''. CI C E " M >. o ,..,
C =:e. 0
4., 0 C
8 2 cl E
c m CU
&- "
>" -0 .., .0 >. 0. c 0-
a, m
Opioid Side Effects 0 1 2 1 µ 2 u_
c0
...............................................................................
...............................................................................
........................).......r....).......r...... .....................
Pale Skin : ; ) .. ; ..
: X
: + , + ..
,
Paresthesia I X i
Passing Gas : I : .. I
X X :
Peripheral Edema I X I I
Pinpoint Pupils I I I i
X
Pinpoint Red Spots On the Skin
'¨
Polyuria
Postural Hypotension ................................... : X
Pounding in The Ears ; I I IXi
i)
Pounding in The Ears : ; : ;
.. :Xi :XI
Pressure in The Stomach t I : I X
Problems with Memory
L L
Problems with Muscle Control
Puffiness or Swelling of the Eyelids or Around the Eyes, Face, Lips, Or Tongue
X X : X :
. . t =
Rapid Breathing X X X i
: X
:- . . =
.
Rapid Weight Gain I X X
Rare I I I I
: X i
õ. , õ. :
õ. = - . .= .
Rash IXI I I
I i ix
Rash, Hives, Or Itching I I .. I I
: X i
Redness of The Face, Neck, Arms, And Occasionally, Upper Chest I IXIXl
XI
Redness of The Skin .................................... I I XIX:
i
'¨
Relaxed and Calm X xi
i
.......................................................... -; -; : =
Relaxed and Calm Feeling ; ; ; :
: X
............................................................. 4-- J.= ¨4 :
4-- i :- -- '¨
Restlessness I I I IXi
iX
Rhythmic Movement of Muscles : .......................... ; : ; X
Rhythmic Movement of the Muscles ; I I I
i i X
Runny Nose : ; X : ; X
Seeing Double X
: : = .. :..
Seeing, Hearing, Or Feeling Things That Are Not There X I. X
: X
. . t :
Seizures i i X
Sensation of Heaviness : X :
. . t =
Sensation of Spinning I : X X i
: X
õ.
Severe Constipation IXI I I
IXi lX
Severe Sleepiness X X ......... X
Severe Sleepiness or Unusual Drowsiness x .
.
. + . + .
- + =
Severe Stomach Pain, Cramping, Or Burning I I X
-------- i --t` : 4-- i -- '¨
Severe Vomiting IXI : IXIXi
i
Shakiness and Unsteady Walk
'¨
Shakiness in The Legs, Arms, Hands, Or Feet IX I I i
iX
-t.
Shakiness or Trembling : ................................ I : ; :
i X i
Shaking t I : XIXi
i I
Shivering : ; : ; X
Shortness of Breath ; I : I
i i X
Skin Itching L : X
t : :
z
Skin Rash
Sleepiness X : :
I X
Sleepiness or Unusual Drowsiness X X l :
x
t . , =
:- '
Sleeplessness I I :
i I x
i. .. i- -- ..
i- -=:. : -4
Slow Heartbeat
Slow or Fast Heartbeat I I I i
i x
Slow or Irregular Heartbeat X X X
Slurred Speech I .. IXI iXi
SneezingLLx - LL x_ L JLx - x -
53
CA 03014319 2018-08-10
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cu
=,-, CIJ
RI C cU
4.= 0 aj c
=¨
c ul et. 0 .c
., -0 ===== a 0. "C _ "
''. CI C E " M >. o u
C ..,e- 0
4-, c c
8 2 el E c co cu
,_ 6, tu
..... ,-
>. -a a -ci )... a. c a
Opioid Side Effects 0 1 2 1 µ 2 u_
c0
...............................................................................
...............................................................................
........................).......r....).......r......
Sore Throat : ; X X
Speech Disorder : X i X
ST Depression : X
Stiff Neck : : : : X
Stomach Cramps ........................................... : : :
X
-.. , = .
Stomach Discomfort or Upset : ; C
'¨
Stomach Discomfort, Upset, Or Pain : : C: ;
Xi
= ..õ.. :,=
.......... :.= - -:
: .
Stomach Pain ; ; ; ;
: : X
Stomatitis ; X
Stopping of Heart : ..................................... ; : ;
:Xi :
Stuffy Nose ; : : :
i i X
Stupor X
:
Stupor tremor, Vertigo, Taste Perversion X
=:=. .
Sudden Sweating X
. . =
Sunken Eyes X X X i
: X
=:=. . . .. =
:..
Sweating : X .. X
, . ,
Ci :X X
Sweating or Chills
Swelling of The Abdominal or Stomach Area : : : :
: x
t= ............................................................ t= .. . :
Swelling of The Eyelids, Face, Lips, Hands, Or Feet i : i :
i i X i
Swelling of The Face Fingers Or Lower Legs
Swelling of The Feet or Lower Legs ..................... : : : X
'¨
Swelling of The Hands, Ankles, Feet, Or Lower Legs : = : : i
i X
= ..õ.. ::
.......... :.= - -:
-.. , = .
Swelling of The Hands, Ankles, Or Feet : ; C
........................................................ 4---- i -----+
: 4---- -: :- -- '¨
Symptoms of Overdose : :X:
Syncope ................................................ : X
Taste Perversion ;X:
Thinking Abnormalities : ; : ;
.. : i :X
Thirst X
Thought Abnormalities X
. . =
Thoughts of Killing Oneself X i X :
=:=. . . .. =
:..
Tightness in The Chest X X X X:Xi)(
. . :..
:
Tingling of The Hands or Feet X : X : X
Tinnitus : X
Tiredness : : : :X:
lX
+ , + : +
= - +
Tooth Pain : : : i
i x
Trembling or Shaking of the Hands or Feet :X: : : :
i lX
Tremor :X:
Trouble Breathing : : x
'¨
Trouble Concentrating X:Xi
iX
-.. , = .
Trouble in Holding or Releasing Urine : ................. : : ;
:Xi :
Trouble Sleeping ; : : (:
i iX X
= -,... -;
¨;..... -; - :
% % : .
Trouble with Gums : ; : ;
.. : : : X ;
Trouble with Speaking t : : X
Trouble with Speaking or Hoarseness .
L L : X :
.. z . = ,
=-- .
-;-
Trouble with Teeth : : X
z
+ L L .. =
L :
Troubled Breathing or Swallowing : X
Troubled Breathing with Exertion l : x
. . = :.. -- 4 --
Tunnel Vision : : . .
Z
X
Twitching : X
+ .....................................................................
Ulcers, Sores, Or White Spots in The Mouth ix
Unable to Sleep : : .. : :
: : X
Uncomfortable Swelling Around the Anus : : X
: + : -.=
, + : ,
Unconscious : : : x
54
CA 03014319 2018-08-10
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OJ
M C 0)
0.1
g a.
cu a. -C
-0 o_ -0
C 8 .E E
7" 2
0 0
C.) ,_==== QJ
.=
X >.= "" >.= X
al 0
Opioid Side Effects s 0 xs 2, xs 0
u.,c0
Uncontrolled Eye Movements õ
--------------
Unsteadiness, Trembling, Or
Ot-h-er Problems with Muscle Control or Coordination
Unusual Bleeding or Bruising
õ ,
Unusual Drowsiness, Dullness Tiredness Weakness Or Feeling f Sluggishness
titit iXi
Unusual Excitement, Nervousness, Or Restlessness
Unusual iire-Jness = X
Unusual Tiredness or Weakness X X
XiXi)OX
Unusual Weight Gain or Loss X X X
L = L
Upper Abdominal or Stomach Pain x z
. = z
Urinary Retention X
=-=`it
Vertigo X
,
Very Slow Heartbeat
-== -==
Voice Alteration )(
Vomiting õ õ i
Is X
Weak or Feeble Pulse X
Weakness Vomiting of Material That Looks Like Coffee Grounds, Severe and
Continuing X
Weight Gain
õõõ õ õõõõõõ : = : =
Weight J-_oss tititi
WeltsWheezing
_
õõ,õõõ õ õ,õ --
--------------------------------
Withdrawal Syndrome (With and Without Seizures) X
L
Wrinkled Skin X X0(i iX
[000175]
Opioids in the development pipeline can utilize the Invention to capture
required
clinical trial information and control opioid dispensing for regulatory drug
approval as well as to
control opioid dispensing after regulatory approval.
All in development opioids are
encompassed in the embodiment of the invention by reference. The FDA and like
regulatory
agency general and opioid specific approval self-assessment, self-testing,
self-reporting, digitally
captured diagnostic testing, digital diary information, dispensing
information, etc. drug approval
recommended data capture and reporting guidelines are incorporated by
reference. The listing
for each opioid includes, by definition, each opioid's respective
indication(s), strength, dosage
form, route of administration, side effect profile, drug interactions, and
regulatory approval
guidelines, etc.
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[000176]
Oral opioid mechanisms of action for marketed oral opioid drugs, oral opioid
drugs
in developed, and efficacious oral opioid drugs withdrawn from the market due
to dose related
side effects or whose development was stopped due to a side effect(s) that can
be addressed by
the embodiment and thereby made approvable are incorporated by reference. The
listed drugs in
the following databases are encompassed in the embodiment of the invention by
reference:
CortellisTM Competitive Intelligence by Thomson Reuters; Adis R&D; and
Pharmaprojects by
Citeline.
The listing for each includes by definition each respective drug's respective
indication(s), strength, dosage form, route of administration, side effect
profile, drug interactions,
mechanisms of action, etc.
[000177]
Oral opioids listed in the following databases that (i) were in development
but were
discontinued due to dose related side effects whose safety concerns can be
addressed by the
Invention or (ii) drugs that were withdrawn from the market after approval due
to dose related
side effects whose safety concerns can be addressed by the Invention and
contained in the
following databases: (i) CortellisTM Competitive Intelligence by Thomson
Reuters, and/or (ii)
Adis R&D, and/or (iii) Pharmaprojects by Citeline are all encompassed in the
embodiment of the
invention by reference. The listing for each drug includes each drug's
respective indication(s),
strength, dosage form, route of administration, side effect profile, drug
interactions, mechanisms
of action, regulatory approval guidelines, etc.
III. System and Method to Control the Delivery of Oral Opioids
[000178]
Various embodiments will be described hereinafter with reference to the
accompanying drawings. These embodiments are illustrated and described by
example only and
are not intended to be limiting. Alternate embodiments may be devised without
departing from
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the spirit or the scope of the invention. Additionally, well-known elements of
exemplary
embodiments of the invention will not be described in detail or will be
omitted so as not to
obscure the relevant details of the invention. Further, to facilitate an
understanding of the
description discussion of several terms used herein follows.
[000179] The word "exemplary" is used herein to mean "serving as an
example, instance, or
illustration". Any embodiment described herein as "exemplary" or "example" is
not necessarily
to be construed as preferred or advantageous over other embodiments. Likewise,
the term
"embodiments of the invention" does not require that all embodiments of the
invention include
the discussed feature, advantage or mode of operation.
[000180] Further, many embodiments are described in terms of sequences of
actions to be
performed by, for example, elements of a computing device. It will be
recognized that various
actions described herein can be performed by specific circuits (e.g.,
application specific
integrated circuits (ASICs)), by program instructions being executed by one or
more processors,
or by a combination of both. Additionally, these sequences of actions
described herein can be
considered to be embodied entirely within any form of computer readable
storage medium
having stored therein a corresponding set of computer instructions that upon
execution would
cause an associated processor to perform the functionality described herein.
Thus, the various
aspects of the invention may be embodied in a number of different forms, all
of which have been
contemplated to be within the scope of the claimed subject matter. In
addition, for each of the
embodiments described herein, the corresponding form of any such embodiments
may be
described herein as, for example, "logic configured to" perform the described
action.
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[000181] FIG. 1 illustrates an exemplary embodiment of the present
invention of a closed
loop system to control opioid diversion, misuse, abuse, double dosing,
addiction, dependence,
overdose, and deaths.
[000182] The following are exemplary descriptions of the FIG. 1 embodiments
of the
invention and how different components relate one to the other and how
together they contribute
to a closed loop opioid traceability and control system:
[000183] The Prescriber 2 is identified via his (i) National Provider
Identification (NPI)
number, (ii) DEA Registration Number, (iii) state medical license number,
and/or (iv) other
association and/or government identification number. This number is related to
the Patient 6 on
the Prescription 4 and the prescription fulfillment Pharmacy 8.
[000184] The Prescription 4 is specific to the Patient 6 and is related to
the Prescriber 2,
Pharmacy 8, the Patient's 6 prescription database file on the Data Servers 10,
and the Opioid
Specific App 12. The Prescription 4 information is electronically or manually
loaded and related
to the Data Servers 10 and the Opioid Specific App 12.
[000185] The Patient 6 is related to the Prescriber 2, Prescription 4,
Pharmacy 8, the Data
Servers 10, the Opioid Specific App 12, the Interface Device 14, the Drug
Dispenser 16, the
individual Drug Cassette 18 (which in some embodiment of the invention may be
an integral
component of the Drug Dispenser 16), and any RFID 20 enabled device which is
incorporated
with the oral dosage form to indicate when the drug has been ingested, any
program which
allows the Patient 6 to take a Selfie 21 of themselves taking the opioid that
is automatically
recognized by the program.
[000186] The Pharmacy 8 is related to the Patient 6 and the Prescriber 2
when the e-
prescription is entered by the Prescriber 2 and/or the Pharmacy 8 receives the
Prescription 4; and
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to the Data Servers 10 when the Prescription 4 is first filed by the
Prescriber 2 and/or filled by
the Pharmacy 8 and to the Opioid Specific App 12 when it is subsequently
created by the App
Generation Program 200 and then when it is downloaded to the Interface Device
14.
[000187] The Data Servers 10 are related to the Patient 6 when the
Prescriber 2 files an
electronic Prescription 4 or when the Pharmacy 8 fills the Prescription 4 and
enters the
Prescriber's 2 Patient 6 specific Prescription 4 instructions. Upon receipt of
the Patient's 6 and
the Prescription 4 information, the App Generation Program 200 on the Data
Servers 10 create
an Opioid Specific and Patient Tailored App 12 which contains a personalized
Patient 6 tailored
Drug Specific Dispensing Algorithm 13. In addition to the Patient 6,
Prescriber 2, prescription
number, pharmacy 8, drug, strength, and dosing schedule information, the
Prescription 4 may
contain specific Patient 6 self-assessment, self-test, self-report, or
digitally captured Patient 6
information/data which may be incorporated into the Drug Specific Dispensing
Algorithm 13 or
which may be captured to assist the Prescriber 2 or other healthcare
professionals in managing
the Patient 6 or to capture information required for drug regulatory
submissions during clinical
trials. The data capture may include patient information requested by the
Prescriber 2 which is
not utilized by the Drug Specific Dispensing Algorithm 13 to make a dispense,
or not, decision,
i.e., keep the Drug Dispenser 16 locked or unlock the Drug Dispenser 16 and
allow an opioid
dose to be dispensed decision.
[000188] The dispensing information for the RFID Pill 20 and/or the Selfie
21 may be
captured using an API with the respective program to close the Closed Loop
Opioid Traceability
and Control or the data can be aggregated by the Data Servers 10 from the
Patient's 6 Electronic
Medical Record 24. This would then provide complete pill by pill opioid
traceability from the
time the opioid is loaded into the Drug Cassette 18 until it is consumed by
the Patient 6. If the
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data servers are authorized to access the Patient's 6 Electronic Medical
Record in keeping with
HIPPA and other governmental guidelines, an API can be utilized to access the
consumption
data in the Electronic Medical Record 24, update the Patient's 6 database on
the Data Servers 10
and thereafter update the information on the related Opioid Specific App 12.
This will provide
true opioid traceability and accountability.
[000189] The Opioid Specific and Patient Tailored App 12 is generated by
the Data Servers
and specifically configured/personalized based upon the prescription
dispensing instructions
and the side effect(s) or values that the Prescriber 2 wants monitored. This
information may or
may not be factored into the Drug Specific Dispensing Algorithm 13 for the
Patient 6. Once the
Opioid Specific App 12 is generated, it is given a specific Patient 6
identification number 160
that ties the Opioid Specific App 12 to the Patient 6. When the Opioid
Specific App 12 is ready,
the Data Servers 10 send an email and/or text message (and/or other similar
communication)
with the Opioid Specific App 12 download link for the Patient 6 to download
the App onto
his/her Interface Device 14 or Devices 14 and/or Standalone Drug Dispenser 16.
At the same
time, the Data Servers 10 add the Patient 6 to the respective Data Server's 10
Patient Database
152 files to facilitate receipt of the Opioid Specific App 12 aggregated and
thereafter
communicated Drug Dispenser 16 serial number, Drug Cassette 18 serial number,
drug NDC
number, batch number, Prescription 4 expiration/beyond-use date, drug storage
requirements,
and related Drug Dispenser Identification No. 158 and Opioid Specific App 12
uploaded drug
specific events, alerts, and information. Simultaneously, the Data Servers 10
define available
Electronic Medical Record 24 links and create a relationship(s) between all
Patient 6 related
information/data files on the Data Servers 10 to facilitate data aggregation,
analysis, querying,
and reporting, etc.
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[000190] The Interface Device 14 is where the Opioid Specific App 12
resides for tethered
Drug Dispensers 16. The Opioid Specific App 12 is tied to the Interface Device
14 through its
telephone number and/or IP address. The Opioid Specific App 12 utilizes the
Interface Device's
14 memory, processor, speaker, camera, biometric authentication,
communications connections
(Bluetooth, Wi-Fi, Internet, etc.), phone, and other features to enable the
Opioid Specific App 12
to control the Drug Dispenser 16 and communicate (e.g., through screen
messages, vibration
alerts, alarms, via sending emails, text messages, or making phone calls,
etc.) with the Patient 6,
the Data Servers 10, the Integrated Call Center 22, the Prescriber 2, other
healthcare
professionals and caregivers, the Pharmacy 6 (e.g., for refills, etc.), etc.
[000191] The Drug Dispenser 16 is related to the Opioid Specific App 12 via
the exchange of
the Drug Dispenser's Identification Number 158 and/or unique serial number
which is
exchanged with the Opioid Specific App 12 during the first wireless
connection/handshake.
Thereafter, the Opioid Specific App 12 utilizes the Drug Dispenser's 16 serial
number to ensure
it is connected with the Patient's 6 Drug Dispenser 16 containing the desired
opioid. Once
verified, the Opioid Specific App 12 controls opioid dispensing by the Drug
Dispenser 16 and all
other Drug Dispenser 16 functions and communications.
[000192] The Drug Cassette 18 has a unique cassette serial number that is
related to the
opioid's NDC number and unique batch number along with opioid specific
information. The
Drug Cassette 18 docks into the Drug Dispenser 16 or is an integral part of
the Drug Dispenser
16, at which time the Drug Dispenser 16 and the Drug Cassette 18 use the Drug
Dispenser's 16
same serial number, depending on the Drug Dispenser's 16 design (the drug
cassette's 18 keep
their own serial numbers in reusable, multidrug drug dispensers 16). Upon
docking, the Drug
Cassette 18, which comes related to a specific opioid and opioid batch number,
becomes related
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with the Drug Dispenser 16 which is in turn related to the Opioid Specific App
12, the Data
Servers 10, the Pharmacy 8, the Prescription 4, the Prescriber 2, and the
Patient 6. The
information related to the opioid contained in the Drug Cassette 18 is
utilized by the Opioid
Specific App's 12 Drug Specific Dispensing Algorithm 13. The Drug Cassette is
in turn related
to the Drug Dispenser 16 which is related to the Opioid Specific App 12 which
is related to the
Patient 6, thereby providing a closed traceability and control loop. The ideal
would be to have an
Opioid traceability and control loop that show that the specific dosage form
in ingested by the
Patient 6.
[000193] The RFID Pill 20 is an oral dosage form that contains a chip which
transits a signal
when it is ingested. The Opioid Specific App 12 can be configured, using an
API, to pick up the
signal and to capture the ingestion information. The time interval between
when the oral dosage
form is dispensed and ingested is indicative of whether the dosage is being
taken by the Patient 6
or potentially diverted. The RFID chip is related to the RFID Pill 20 which is
in turn related to
the Drug Cassette 18. The Drug Cassette is in turn related to the Drug
Dispenser 16 which is
related to the Opioid Specific App 12 which is related to the Patient 6,
thereby providing a closed
traceability and control loop.
[000194] The Selfie 21 recognition software is designed to recognize both
the Patient 6 and
the solid dose medication, opioid, the Patient 6 is taking. The Patient 6 is
tied to the Drug
Dispenser 16 and the related Drug Cassette 18 and the related opioid. The time
interval between
when the opioid is dispensed by the Drug Dispenser 16 and the time the opioid
is captured as
being taken by the Patient 6 is indicative of Patient 6 prescription
compliance or opioid
divergence. If the opioid is an RFID Pill 20, then there is full confirmation
that the Patient 6 did
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in fact take the dispensed opioid ¨ closing the traceability and control loop
for the individual
opioid pill.
[000195] An Electronic Medical Record 24 is created by the Data Servers 10
at the same time
that the first Opioid Specific App 12 is created for the Patient 6. The
Electronic Medical Record
24 is configured to be discoverable by authorized care givers using a National
Record Locator
Service (NRLS) like SureScripts. The Electronic Medical Record 24 is
configured for
dispensing information and to present any data captured by the Opioid Specific
App 12 and any
medically pertinent communications between the Patient 6 and the Integrated
Support Center 22
from the interactions logs. This data is automatically updated by the Data
Servers 10. The
Electronic Medical Record 24 can also be utilized to check to ascertain if any
other prescriptions
are current for medications which may be in conflict with any new or existing
opioid
Prescription 6.
[000196] FIG. 2 illustrates an exemplary embodiment of the present
invention, an integrated
drug dispensing and patient management system composed of a Opioid Specific
App 12 which
contains a Drug Specific Dispensing Algorithm 13 resident on an Interface
Device (Smartphone,
computer Tablet, portable or desktop computer, standalone drug dispenser, etc.
with Bluetooth,
Wi-Fi, and/or Internet communications capabilities) 14 used to control
dispensing by a (single or
multidrug) Drug Dispenser 16; an Integrated Support Center 22; a Patient 6; a
Prescriber 2; and
the Patient's Electronic Medical Record 24.
[000197] FIG. 3 is an exemplary embodiment depicting the Prescription
Interface Module 30
which is designed to integrate data entry with the respective generally used e-
prescribing
programs (e.g., ADSC MedicsRx, Allscripts, DAW Systems, DrFirst Rcopia, MDT
Toolbox-Rx,
Medtab RxCure, OA Systems, Practice Fusion, RxNT eRx, Spectra eRx, etc.)
and/or pharmacy
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prescription systems (e.g., OmniCare, QS/1, PharMerica, Frameworks, etc.)
and/or national
record locator services (NRLS), such as the one offered by SureSripts, via an
application
program interface (API). The requested information can be directly entered by
the Prescriber 2
and simultaneously submitted to Pharmacy 8 and its Pharmacy Database 164 as
well as the
Integrated Support Center's 22 Patient Database 152. Any data that was not
entered by the
Prescriber 2 can be entered at the Pharmacy 8. These updates are automatically
uploaded to the
Patient Database 152. Any data that was not entered by either the Prescriber 2
or the Pharmacy 8
can be entered by the Patient 6. However, the information that can be entered
by the Patient 6
using direct data entry onto the Opioid Specific App's 12 prescription
information screen is
limited to Alerts Information 116 to 146. The Patient 6 entered data is
automatically uploaded
and synchronized by the Opioid Specific App 12 with the Patient Database 152.
[000198] The Prescription Interface 30 captures the Patient's Full Name 32,
Patient's Street
Address 34, Patient's Date of Birth 36, Patient's Gender 38, PBM/Payer Unique
Member
Identification Number 40, Cardholder's ID Name 42, Group ID 44, Diagnosis Code
(ICD-10,
ICD-11, etc.) 46, Prescriber's Full Name 48, Prescriber's Full Address 50,
Prescriber's Phone
Number 52, Prescriber's Fax Number 54, Supervisor Identity No. 56,
Prescriber's Agent Identity
58, Prescriber's National ID (NPI) 60, Prescriber's DEA No. 62, Prescriber's e-
Prescription
Network or Vendor ID 64, Prescription Issuance Date 66, Drug Name 68, Drug NDC
(National
Drug Code No.) 70, (Drug) Strength 72, Dosage Form 74, Prescribed Drug
Quantity 76,
Directions For Use 78, Dosage Frequency 80, Minimum Time Between Doses 82,
Maximum
Daily Dose 84, Maximum Dosing Days 86, Refills Authorized 88, Product
Substitution Code 90,
Notes Field 92, Prior Authorization Code 94, Store (Pharmacy) Name 96, (Store)
Street Address
98, (Store) Telephone Number 100, NCPDP (National Council for Prescription
Drug Programs)
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ID 102, Prescription Expiration Date (Beyond-use date which is the earlier of
the drug expiration
date or the Prescription Expiration Date) 103, Drug Storage Temperature
(Range) 104, Drug
Storage Humidity (Range) 106, Additional Information To Track (these are
additional digitally
captured patient values and/or self-assessment, self-test, and/or self-
reported patient information
the Prescriber 2 wants tracked for better Patient 6 management and/or to
capture clinical trial
required information for regulatory submissions) 108, Side Effects To Track
(this represents
specific opioid mediated side-effect(s) digitally captured patient values
and/or self-assessment,
self-test, and/or self-reported Patient 6 information the Prescriber 2 wants
tracked to better
manage the Patient 6) 110, Prescriber's Electronic or Digital Signature 112,
[000199] Check and Request Completion if Data Missing 114 is the program
routine to
ensure all the requisite Prescription 4 data is captured. The Alerts
Information is used by the
Standalone Drug Dispenser 16 or the Opioid Specific App 12 to advise
caregivers and/or family
members when a Patient 6 dispenses or ingests (in the case of an RFID Pill 20
or Selfie 21
ingestion confirmation) the opioid and for special advisories if some kind of
intervention or
action may be required. The type of alert sent to each individual can be
designated in the
Prescription Interface or when the information is directly entered by the
Patient 6 into the Opioid
Specific App 12 or the Standalone Drug Dispenser 16. The following are
examples of the data
capture fields for the Alerts Information: Alerts Selection and Timing 116,
Prescriber's Name
118, Prescriber's Email 120, Prescriber's Texting Telephone No. 122, Disease
Manager Name
124, Disease Manager Email 126, Disease Manager Texting Telephone No. 128,
Relative No. 1
Name 130, Relative No. 1 Email 132, Relative No. 1 Texting Telephone No. 134,
Relative No. 2
Name 136, Relative No. 2 Email 138, Relative No. 2 Texting Telephone No. 140,
Relative No. 3
Name 142, Relative No. 3 Email 144, Relative No. 3 Texting Telephone No. 146.
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[000200] FIG. 4 is an exemplary embodiment of the logic to: (i) enter the
Prescription 4
information into the Pharmacy Database 164 and (ii) into the Patient Database
152 and (iii) to
generate a Dispenser Identification Number 158 and (iv) Patient Identification
Number 160
which are required to create the Opioid Specific App 12 and thereafter for
dispensing the
medication doses. The Dispenser Identification Number 158 is a unique
identifier that is utilized
to link the Prescription 4 to one or more prescribed Drug Dispenser 16 serial
numbers. Once
the Dispenser Identification Number 158 exists the logic proceeds to generate
and the Patient 6
and Opioid Specific App 12 and transmit it to the Patient 6 for downloading
into their Interface
Device 14 or Devices 14. After it is enabled by the Patient 6, the Opioid
Specific App 12 is
ready to control Opioid dose dispensing once the App 12 is tied to one or more
Drug Dispensers
16.
[000201] The restricted Dispenser Identification Number 158 is issued in
response to the type
of medication prescribed. If the medication is one where, for example,
divergence is a concern,
as with Opioid, then the restricted Dispenser Identification Number 158 is
issued by the Data
Servers 10 when the prescription is Submitted 150. The restricted Dispenser
Identification
Number 158 restricts opening of reusable Drug Dispensers 16 and docking of the
Opioid
containing Drug Cassette 18 to authorized medical professionals.
[000202] When the Prescriber 2 or the Pharmacist (Pharmacy) 8 Submits 150
the
ePrescription 4 it results in the Pharmacy Database 164 and Patient Database
152 being
automatically updated/synchronized. Then it checks to see that the required
Dispenser
Identification Number 158 already exists for the prescribed Opioid for the
Patient 6 or if the
Dispenser Identification Number 158 need to be generated for the prescribed
Opioid medication
154. If the answer is No 156, then the program issues the restricted Dispenser
Identification
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Number 158 and automatically sends it to the Pharmacy Database 164 and Patient
Database 152
for inclusion with the Prescription 4. It then checks for a Patient Identifier
Number 160 which is
used as the control number and identifier for all Patient 6 data stored on the
Data Servers 10 and
the Patient Database 152. If none exists, the program generates a Patient
Identifier Number 160.
The program automatically emails and/or texts the Patient Identifier Number
160 to the Patient 6
for use by the Patient 6 when initially setting up the Opioid Specific App 12.
[000203] If a Dispenser Identification Number 158 exists, Yes 166, then the
system is ready
to Proceed To Dispense 168. Upon confirmation of the Dispenser Identification
Number 158,
then the program checks the Patient Database 152 to ascertain if there is
another dispenser 172
for the prescribed medication. If there isn't another Drug Dispenser 16 for
the specific
medication, No 174, the Opioid Specific App 12 on the Patient Database 152 is
set to allow
dispensing to proceed 176 per the Prescription Instructions 4.
[000204] If another Drug Dispenser 16 for the drug medication is
identified, Yes 178, then
the program checks to see if there is another dispenser 172, if No 174, then
the program is ready
to proceed with the Dispense 176 process. However, if there is another
dispenser 172, Yes 178,
then the program proceeds to check if all the doses in the first Drug
Dispenser 16 have been
dispensed 180. If the answer is Yes 182, then the Opioid Specific App 12 is
authorized to
proceed with dispensing 184 from the new or additional Drug Dispenser 16 per
the Prescription
4 instructions. If the answer is No 186 that not all the medication has been
dispensed 180 from
the first Drug Dispenser 16, then: (i) the second or subsequent Drug Dispenser
16 remains
locked, restricted from dispensing, until the drug in the first Drug Dispenser
16 is fully
dispensed, or (ii) the first Drug Dispenser 16 remains locked and the Second
or Subsequent
Dispenser 16 is allowed to begin dispensing 188 per the Prescription 4. The
program guards
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against dispensing of more than one authorized dose from any one or multiple
Drug Dispensers
16. Simultaneously, a message/alerts 190 are generated informing the Patient 6
that the drug in
the first Drug Dispenser 16 needs to be fully dispensed before it expires.
[000205] FIG. 5 is an exemplary embodiment depicting an Opioid Specific App
12 which
resides on an Interface Device 14 or on a Standalone Drug Dispenser 16 and
controls drug dose
dispensing from a Drug Dispenser 16. When the Patient 6 is prescribed an
Opioid, the Patient 6
is trained on the operation of the Drug Specific Dispensing App 12 and the
related Drug
Dispenser 16 using the App's Training Module 236.
[000206] In this embodiment of the invention, the Opioid Specific App 12 is
comprised of the
following software modules: (i) Biometric Authentication 202, (ii)
Prescription Information 204
module which can be programmed remotely by the Integrated Support Center 22,
(iii) the Patient
Reminder 205 module (iv) the Interface Device(s) API(s) 206 module, (v)
Patient Self-
Assessment 208 module which is unique for each drug, (vi) Patient Self-Test
210 module which
is unique for each drug, (vii) Patient Self-Report 212 module which is unique
for each drug,
(viii) Digital Capture (APIs) 214 module, (ix) Data Aggregation 215 module (x)
the Interface
Database 216, (xi) the Prescriber Side Effect Tracking Preferences 218 module,
(xii) the
Dispensing Algorithm 220 module which is unique for each drug and which may be
personalized
for each patient, (xiii) Communication and Reporting 222 module, (xiv) the
Central Servers Data
Sync 224 module, (xv) the Patient Reporting 226 module, (xvi) Drug Replacement
Cassette 227
module, (xvii) the Package Insert 228, (xviii) Dispenser Manual 230, (xix) the
Opioid Specific
App Manual 232, (xx) the Help and Troubleshooting 234 module, (xxi) the
Training Module
236, and (xxii) the Unique App Serial Number 238.
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[000207] The following are exemplary descriptions of the FIG. 5 embodiments
of the
invention:
[000208] The App Generation Program 200 is automatically triggered when an
e-Prescription
is Submitted 150 to the Patient Database 152. It then proceeds to build each
of the following
modules, which are specific for each drug and each patient, into an Opioid
Specific App 12.
[000209] Biometric Authentication module 202 encompasses the utilization of
a biometric
authentication screen and/or digital interface which allows the patient, upon
authentication, to
automatically move to the first Drug Specific Dispensing Algorithm 13 screen.
The Biometric
Authentication 202 can constitute one or a combination of more than one
biometric
authentication method. Examples include Iris Scanning systems, Retinal
Scanning systems,
Fingerprint Scanning systems, Password Sign-on systems, Facial Scanning
systems, Voice
Scanning systems, Gesture Recognition systems, automatic server generated
temporary password
systems, etc.
[000210] Biometric Authentication 202 can also be utilized as a diagnostic
input that can be
used by the Drug Specific Dispensing Algorithm 13. As an example, Iris
Scanning can be
utilized for both Biometric Authentication 202 and as a Patient Self-
Assessment 208 digital
input. The Opioid Specific App 12 could use the Patient's 6 base and/or
trended iris scans to
ascertain changes in pupil size to ascertain if the Patient 6 is evidencing
the "pinpoint pupils"
or "Mydriatic pupils" that are a sign of opioid overdose (e.g., opioid
overdose). The
algorithm would make the appropriate adjustments for lighting conditions,
distance, etc. and
the Patient's 6 individual pupil dilation characteristics in making its
determination.
[000211] As part of the Biometric Authentication 202 process, after the
Biometric
Authentication 202 recognizes the Patient 6, the program: (i) effectuates a
handshake/connection
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with the Drug Dispenser 16, (ii) checks to ensure that the drug has not
expired 103 (is not past its
Expiration/Beyond-Use Date), (iii) that the opioid has been stored within
prescribed temperature
104 and humidity 106 parameters, (iv) checks the Prescription 4 information to
ensure the
Patient 6 is authorized to dispense the dose (the dose is within prescribed
Prescription 4
parameters, (v) validates that the Drug Dispenser's 16 serial number 450 is
registered to the
Patient 6, and then effectuates handshakes/connections with designated digital
devices to
download specific digitally captured patient values or information 852, 854,
856, 857, 858, 859,
860.
[000212] If the Biometric Authentication 202 does not recognize the Patient
6, it asks the
Patient 6 to try again. After a given number of tries, it alerts the patient 6
to contact the
Integrated Support Center 22 and alerts the Integrated Support Center 22 of
the failed attempts
and lists the Patient 6 for a follow-up call by the Integrated Support Center
22 if the drug has not
been properly dispensed within a specific timeframe.
[000213] If the Opioid Specific App 12 does not recognize the Drug
Dispenser 16, the Patient
6 gets an alert screen explaining why it does not recognize the Drug Dispenser
16, this may
include but is not limited to: (i) unable to locate the Drug Dispenser 16,
(ii) the Drug Dispenser
16 does not have the right serial number, (iii) the prescribed drug has not
been fully dispensed
from the other Drug Dispenser 16, etc. Simultaneously, if the Opioid Specific
App 12 ascertains
that the Drug Dispenser 16 does not have the right serial number 450, it will
send a message to
the Integrated Support Center 22 indicating the serial number of the
recognized Drug Dispenser
16 for follow-up action by the Integrated Support Center 22. One alternative
for the Integrated
Support Center 22 is to lock the Opioid Specific App's 12 screen to only give
the Patient 6 the
choice of calling the Integrated Support Center 22 to resolve his dispensing
issue, another is to
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lock the previous Drug Dispenser 16 which contains undispensed medication and
authorize
dispensing to resume using the new Drug Dispenser 16. The process can be
automated or
programmed to require intervention by an Integrated Support Center 22
representative.
[000214] The Prescription module 204, which is unique for each opioid,
encompasses the
ability of the Prescriber 2, the Pharmacy 8, other authorized healthcare
professionals, or the
Integrated Support Center 22 to input some or all the Prescription 4
information. Clicking on
Submit 150 in the respective API interfaced e-Prescription 4 program (e.g.,
ADSC MedicsRx,
Allscripts, DAW Systems, DrFirst Rcopia, MDT Toolbox-Rx, Medtab RxCure, OA
Systems,
Practice Fusion, RxNT eRx, Spectra eRx, etc.) and/or pharmacy prescription
programs/systems
(e.g., OmniCare, QS/1, PharMerica, Frameworks, etc.) and/or Electronic
Prescribing Networks
(e.g., SureScripts - that seamlessly connects Prescribers 2 with Pharmacies 8)
loads the data into
the Patient Database 152. The Prescription 4 data is then automatically
integrated into the
Opioid Specific App 12 and/or into any subsequent Opioid Specific App 12
updates by the App
Generation Program 200. Additional data input may be inputted by Prescribers 2
and/or the
Pharmacy 8 through the application program interface (API) with the e-
prescribing
programs/systems. When the update is submitted, the App Generation Program 200
automatically syncs all inputs and updates the Patient's 6 Opioid Specific App
12 in the Patient
Database 152 as well as the Interface Database 278 if the Opioid Specific App
12 has been
previously downloaded onto the Interface Device 14 or Standalone Drug
Dispenser 16.
[000215] When loading the Drug Cassette 18 into the Multiple Use Drug
Dispenser 16, the
application program interface (API) enables the Pharmacy 8 or another
healthcare professional
dispensing the opioid to enter the required drug's Brand and/or generic name,
strength/dosage,
NDC number, Batch Number, drug temperature storage range, drug humidity
storage range, and
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the drug's expiration/beyond-use date. This input can be done manually and/or
via a barcode
scan of the Individualized Drug Cassette 18.
[000216] The prescribing information defines the dosing strength and
administration schedule
(e.g., q.d., b.i.d., t.i.d., q.i.d., q.h.s., -X a day, -X per week, -X per
month, q.4h, q.6h, q.o.d., a.c.,
p.c., pm, etc.). The pm dosing, and/or for example the patient self-analgesia
dosing, can be
designated to allow the Patient 6 to self-medicate using multiple smaller
doses to a maximum
cumulative dose over a specified time period. Once the maximum dose is
dispensed, the Drug
Dispenser 16 is locked by the Opioid Specific App 12 until the next dosing
period begins and the
patient enters the requisite information to enable the Opioid Specific App 12
to signal the Drug
Dispenser 16 to dispense. This in effect allows for "Oral Patient Controlled
Analgesia" and or
patient symptomatic control for certain conditions, e.g., breakthrough pain.
[000217] Once the Prescription Information 204 is entered and the Drug
Cassette 18 is loaded
and locked into the Drug Dispenser 16, the App Generation Program 200
establishes the Patient
6 dose reminder schedule. Reminders include but are not limited to the ability
of the Opioid
Specific App 12 to alert the Patient 6 using different methodologies. Examples
include: (i)
automatically bringing up the Biometric Logon screen 850 and buzzing the
Interface Device 14,
and/or (ii) initiating a phone call with a recorded reminder message, and/or
(iii) sending an email
message, and/or (iv) sending a text message, and/or (v) having the Integrated
Support Center 22
call the Patient 6, and/or (vi) send an alert to a caregiver or family member
if the medication has
not been taken within a specific time after the dose was supposed to be
taken/dispensed, etc. The
sequence of reminders can be specified for each patient.
[000218] When it is time to dispense the medication and/or when a reminder
to take the drug
is initiated, the Opioid Specific App 12 is shown on the Interface Device's
screen. When the
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Interface Device 14, for example a smartphone, is turned on or unlocked, the
screen
automatically moves to the Biometric Authentication 850 screen. If the Opioid
Specific App 12
is clicked on the screen of an Interface Device 14 or on the screen of a
Standalone Drug
Dispenser's 16 screen opens to the Biometric Authentication 850 screen.
[000219] The Patient Reminder 205 module which utilizes the Dosing
Frequency 80 to bring
up the Opioid Specific App 12 screen on the Interface Device 14 or Standalone
Drug Dispenser
16 when it is time to dispense the medication. If the medication is not
dispensed within a
specified timeframe, the program will cause the Interface Device 14 to vibrate
and/or send the
Patient 6 an email or text message to remind him/her to take the medication.
If after a designated
time interval, if the Patient 6 has not dispensed the medication, then the
program will send alert
notifications to the designated and authorized Prescriber 118, Disease Manager
124, Relative
130, 136, 142, etc. If after an additional elapsed time the Patient 6 has not
dispensed the
medication, the program will send an alert to the Integrated Call Center 22 to
call the Patient 6 to
ascertain why he/she has not dispensed the medication.
[000220] The Interface Device API 206 module utilizes the Interface
Device's 14 Bluetooth
and/or Wi-Fi communications capability along with specifically written
application program
interfaces (APIs) to interface, handshake/communicate, with the Drug Dispenser
16, the Patient
Database 152, the Integrated Call Center 22, third-party programs resident on
the Interface
Device 14 (e.g., Patient Diaries 852), and designated, prescribed, patient
monitoring and/or
diagnostic devices designed to capture digital patient values and/or
observations 854, 856, 857,
858, 859, 860, etc. These APIs allow programs and devices to communicate with
one another
and enable the Opioid Specific App 12 to aggregate prescribed information as
well as the patient
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information required for the Drug Specific Dispensing Algorithm 13 to make a
dispensing
decision.
[000221] The App Generation Program 200 only adds independent diagnostic
and/or
monitoring device APIs, from the API library on the Data Servers 10, to the
Opioid Specific and
Patient Tailored App 12 as required by the Prescription 4. Addition of a
specific monitoring
and/or diagnostic API also integrates the information into the App Manual 232
and the Training
Module 236 and the initial Patient 6 Opioid Specific App 12 setup
instructions/requirements.
[000222] Patient Self-Assessment module 208 is compiled from the Data
Servers 10 Self-
Assessment Routines Database based upon: (i) specific opioid requirements,
and/or (ii)
Prescribed 4 values/information the Prescriber 2 has designated he/she wants
tracked 108, 110
(for better patient management or to manage specific side effects), and/or
(iii) to capture Patient
Reported Outcomes (PRO) information for clinical trials. Opioid specific self-
assessment is
based upon, for example, the opioid's side effects, potential drug
interactions, implications of
under and/or overdosing, efficacy measures, dosing schedule, opioid strength,
single or
multidrug regimen, effects of weight gain, aging, development of
comorbidities, etc. Certain
Patient Self-Assessment 862 screens will, for example, incorporate known self-
assessment
scales, such as the Wong Baker Faces to indicate pain level, or will
incorporate self-assessment
screens specifically developed for the specific drug. As an example, for
opioids, the object of
the Patient Self-Assessment screens 862 is for drug titration and the
management of opioid
tolerance. The screens may also be those which are designed to capture Patient
6 specific
information required by regulatory agencies for the subsequent approval of the
opioid and/or for
post marketing studies.
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[000223] Patient Self-Test 210 module is compiled from the Data Servers 10
Self-Test
Routines Database based upon: (i) specific opioid requirements, and/or (ii)
Prescribed 4
values/information the Prescriber 2 has designated he/she wants tracked 108,
110 (for better
patient management or to manage specific side effects), and/or (iii) to
capture Patient Reported
Outcomes (PRO) information for clinical trials. Patient Self-Testing 864 is
specific for each
opioid based upon the opioid's side effects. As an example, for opioids these
include, but are not
limited to tests to measure confusion, delirium, and/or pinpoint pupils.
Certain Patient Self-
Testing screens 864 will, for example, incorporate known self-tests or will
incorporate self-
testing screens specifically developed for the opioid. Examples include a
motor skills test, a
cognitive impairment test, or having the Patient 6 take a selfie of their face
with the Patient 6
ensuring his/her eyes are open, etc. For opioids, the objectives of the
Patient Self-Testing
screens 864 are to assist in patient management to preclude overdosing, under
dosing, misuse,
abuse, dependence, and/or addiction. The screens may also be those which are
designed to
capture Patient 6 specific information required by regulatory agencies for the
subsequent
approval of the opioid and/or for post marketing studies.
[000224] Patient Self-Report module 212 is compiled from the Data Servers
10 Self-Report
Routines Database based upon: (i) specific opioid requirements, and/or (ii)
Prescribed 4
values/information the Prescriber 2 has designated he/she wants tracked 108,
110 (for better
patient management or to manage specific side effects), and/or (iii) to
capture Patient Reported
Outcomes (PRO) information for clinical trials. The Self-Reporting 866 screens
are specific for
each opioid based upon the opioid's side effects, potential drug interactions,
implications of
under and/or overdosing, efficacy measures, dosing schedule, drug strength,
single or multidrug
regimen, effects of weight loss or weight gain, aging, development of
comorbidities, etc. The
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Self-Reporting screens 864 may (i) include well established reporting scales,
such as the Bristol
Stool Index to indicate if the patient is or is becoming constipated, (ii) a
reporting on other drugs
taken over a specific period of time and/or since taking the last opioid dose
which may
precipitate drug-drug interactions/adverse events, (iii) or symptomology such
as sedation,
dizziness, nausea, vomiting, etc. As an example, for opioids, the objectives
of the Patient Self-
Reporting screens 866 are to help the Patient 6 and the Prescriber 2 to manage
opioid side-
effects, preclude opioid side-effects, and to preclude overdosing. The screens
may also be those
which are designed to capture Patient 6 specific information required by
regulatory agencies for
the subsequent approval of the drug and/or for post marketing studies.
[000225] The Digital Capture (APIs) module 214 is compiled from the Data
Servers 10
Digital Capture API Routines Database based upon: (i) specific opioid
requirements, and/or (ii)
Prescribed 4 values/information the Prescriber 2 has designated he/she wants
tracked 108, 110
(for better patient management or to manage specific side effects), and/or
(iii) to capture Patient
Reported Outcomes (PRO) information for clinical trials. Digital capture
encompasses, as an
exemplary, digital information that is integrated via the Opioid Specific App
12 via Digital
Capture from, as examples, (i) a wearable monitoring device 859, (ii) a
digital scale 858, (iii) a
third-party monitoring App on a smartphone 852, 880 (iv) a hand held
diagnostic device 882, (v)
a lifestyle monitor 884, (vi) a digitalized home diagnostic or self-diagnostic
886, (vii) a
swallowed tracking and/or diagnostic aid, (viii) a drug tracking chip, radio
frequency
identification device (RFID) 856 or Selfie 857, (ix) digital interfaces 860,
and/or care giver or
parent patient assessments and/or journal entries (which may be resident in
other Apps on the
Patient's 6 Interface Device 14, etc.
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[000226] The Data Aggregation 215 module is designed to aggregate all one
time and trended
information from the Drug Dispenser 16, the Drug Cassette 18, other Opioid
Specific App 12
modules, the Patient Self-Assessment 208, Patient Self-Test 210, Patient Self-
Report 212, and
Digital Capture 214 modules and organize and aggregate the data so that it can
be utilized by the
Dispensing Algorithm 220.
[000227] The Interface Database module 216 is designed to populate the
Interface Database
278 that resides on the Interface Device 14 or on the Standalone Drug
Dispenser 16 and is
designed to store information that is continuously synchronized with the
Patient Database 152.
As an example, it aggregates and synchronizes the following: Patient
Information: (i) Patient's
Full Name 440, (ii) Patient's Street Address 442, (iii) Patient's Date of
Birth 444; (iv) Logon
Data Repository 445; Drug Dispenser Information: (v) Dispenser Opening Codes
446
(accommodates more than one dispenser code), (vi) Tamper Attempt History 448,
(vii)
Dispenser Serial No. 450 (accommodates more than one dispenser serial number),
(viii) Drug
Cassette Serial No. 452 (accommodates more than one cassette serial number),
(ix) Drug NDC
No. 454, (x) Drug Batch No. 456 (accommodates more than one batch number),
(xi) Drug
Expiration Date 458 (each tied to a specific batch number), (xii) Drug Storage
Temperature 460,
(xiii) Drug Storage Humidity 462, (xiv) Last Dose Time and Date 464, (xv)
Number of Pills
Remaining 466; Prescription Information: (xvi) Drug Name 468, (xvii) Strength
470, (xviii)
Dosage Form 472, (xix) Prescribed Drug Quantity 474, (xx) Refills Authorized
476, (xxi)
Prescriber's Full Name 478, (xxii) Prescriber's National Provider ID (NPI)
480, (xxiii)
Prescriber's DEA No. 482, (xxiv) Store (Pharmacy) Name 484, (xxv) Prescription
Reference No.
486, (xxvi) Prescription Issuance Date 488; Values Tracking: (xxvii)
Prescription (Dosing
Schedule) 490, (xxviii) Digitally Tracked Values 492, (xxix) Self-Assessment
Values 494, (xxx)
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Self-Test Values 496, (xxxi) Self-Reported Values 498, (xxxii) Concomitant
Medications 499,
(xxxiii) Side Effect Values 500, (xxxiv) Clinical Trial Information 501; Error
Reporting: (xxxv)
Unsuccessful Dispensing Attempts History 502, (xxxvi) Error Codes History 504;
Alerts
Information: (xxxvii) Alerts Selection and Timing 506, (xxxviii) Prescriber's
Name 508, (xxxix)
Prescriber's Email 510, (xl) Prescriber's Texting Telephone No. 512, (xli)
Disease Manager's
Name 514, (xlii) Disease Manager Email 516, (xliii) Disease Manager Texting
Telephone No.
518, (xliv) Relative No. 1 Name 520, (xlv) Relative No. 1 Email 522, (xlvi)
Relative No. 1
Texting Telephone No. 524, (xlvii) Relative No. 2 Name 526, (xlviii) Relative
No. 2 Email 528,
xlix) Relative No. 2 Texting Telephone No. 530, (1) Relative No. 3 Name 532,
(1i) Relative No. 3
Email 534, (lii) Relative No. 3 Texting Telephone No. 536.
[000228] The Prescriber Side Effect Tracking Preferences 218 module is
compiled from the
Data Servers 10 Drug Side Effect Routines Database based upon: (i) Prescribed
4 side effect
information the Prescriber 2 has designated he/she wants tracked 108, 110 (for
better patient
management or to manage specific side effects), and/or (ii) to capture Patient
Reported
Outcomes (PRO) information for clinical trials. Each routine is side-effect
specific and is based
upon the opioid's specific side effects identified during pre- and post-launch
clinical trials as
listed in references such as: Goodman & Gilman's, The Pharmacological Basis of
Therapeutics
(12th Ed) (Goodman et al. eds) (McGraw-Hill) (2011); and 2015 Physician's Desk
Reference
(PDR); CortellisTM Competitive Intelligence by Thomson Reuters; Adis R&D;
and/or
Pharmaprojects by Citeline, etc.
[000229] The Dispensing Algorithm 220 module encompasses, as an example,
the Product
Expiration (beyond-use date) 103 date, Properly Stored information (for
example, temperature,
moisture, etc.) 104, 106, one or more Patient Self-Assessment 494, Patient
Self-Testing 496,
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Patient Self-Reporting 498 and/or one or more Digitally Tracked 492 diagnosis
or monitoring
values, the Dispensing Algorithm 13, the Dispense Screen 868 and interface
with the Drug
Dispenser 16, and patient feedback and instruction screens 870, 872, 874, etc.
The feedback and
instruction screens which are presented are aggregated by the App Generation
Program 200 from
the Data Servers 10 Patient Feedback and Instructions Database. The
instructions are opioid
specific.
[000230] The Communications and Reporting 222 module encompasses, for
example, the
interface between: (i) the Opioid Specific App 12 and the Drug Dispenser 16
via the Interface
Device 14; (ii) the interfaces between the Opioid Specific App 12 and any
proprietary or third-
party digital devices, data aggregation devices, computer databases,
diagnostic devices, and
medication tracking devices, etc., for example, those digital devices listed
under Fig. 18 e.g.,
852, 854, 856, 857, 858, 859, 860, and on FIG. 19, e.g., 858, 880, 882, 884,
886; (iii) the
interface between the Opioid Specific App 12 and the Data Servers 10 and the
respective
databases that store information captured by the Opioid Specific App 12; (iv)
the data and
reports exchanges between the Data Servers 10, the Integrated Support Center
22 and accessed
by the Opioid Specific App 12; (v) the reminder and alerts notifications
initiated by the Opioid
Specific App 12 and communicated to the Patient 6, Prescriber 2, 508, 510,
512, the Disease
Manager 514, 516, 518, and Relatives 520, 522, 524, 526, 528, 530, 532, 534,
536, and/or other
care givers, etc.; (vi) securely handshaking/connecting the Opioid Specific
App 12 to the
Integrated Support Center 22 in keeping with Health Insurance Portability and
Accountability
Act (HIPAA) Patient 6 data security requirements; (vii) synchronization of the
information
captured by the Opioid Specific App 12 with the Integrated Support Center's 22
Data Servers 10;
(viii) sending to and receiving alerts from the Integrated Support Center 22;
(ix) enabling the
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Integrated Support Center 22 to lock or unlock the Drug Dispenser 16; (x)
alerting the Integrated
Support Center 22 of unusual attempts to open the Drug Dispenser 16; (xi) the
ability of the
Integrated Support Center 22 to remotely update the Opioid Specific App 12
software; (xii) in
case of an opioid recall, allows the Integrated Support Center 22 to
immediately lock (preclude
all dispensing) those Drug Dispensers 16 that contain Drug Cassettes 18
containing the opioid
and/or the opioid batch which is being recalled and simultaneously notifying
the Patient 6 what
they need to do; (xiii) enables the Opioid Specific App 12 to access patient 6
reports, charts, and
graphs requested by the Patient 6; (ix) enables the patient 6 to request a
refill prescription to be
sent to his/her pharmacy 8 for refill; (x) enables the Integrated Support
Center 22 to change the
prescription on the Opioid Specific App 12; (xi) enables the interface between
the App
Generation Program's 200 Opioid Specific App 12 software download and update
routines, etc.;
(xii) enables the communications interface between the Opioid Specific App 12,
the Drug
Dispenser 16, and the Integrated Support Center 22 which allows the Integrated
Support Center
22 to troubleshoot problems with either the Opioid Specific App 12 and/or the
Drug Dispenser
16, etc.
[000231] Central Servers Data Sync 224 module is the software module that
automatically
synchronizes the Interface Database 278 and the Patient Database 152. An
example of the types
of data that is synchronized includes but is not limited to: Patient
Information: (i) Patient's Full
Name 440, (ii) Patient's Street Address 442, (iii) Patient's Date of Birth
444; (iv) Logon Data
Repository 445; Dispenser Information: (v) Dispenser Opening Codes 446
(accommodates more
than one dispenser code), (vi) Tamper Attempt History 448, (vii) Dispenser
Serial No. 450
(accommodates more than one dispenser serial number), (viii) Drug Cassette
Serial No. 452
(accommodates more than one cassette serial number), (ix) Drug NDC No. 454,
(x) Drug Batch
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No. 456 (accommodates more than one batch number), (xi) Drug Expiration Date
458 for each
batch, (xii) Drug Storage Temperature 460, (xiii) Drug Storage Humidity 462,
(xiv) Last Dose
Time and Date 464, (xv) Number of Pills Remaining 466; Prescription
Information: (xvi) Drug
Name 468, (xvii) Strength 470, (xviii) Dosage Form 472, (xix) Prescribed Drug
Quantity 474,
(xx) Refills Authorized 476, (xxi) Prescriber's Full Name 478, (xxii)
Prescriber's National
Provider ID (NPI) 480, (xxiii) Prescriber's DEA No. 482, (xxiv) Store
(Pharmacy) Name 484,
(xxv) Prescription Reference No. 486, (xxvi) Prescription Issuance Date 488;
Values Tracking:
(xxvii) Prescription (Dosing Schedule) 490, (xxviii) Digitally Tracked Values
492, (xxix) Self-
Assessment Values 494, (xxx) Self-Test Values 496, (xxxi) Self-Reported Values
498, (xxxii)
Concomitant Medications 499, (xxxiii) Side Effect Values 500, (xxxiv) Clinical
Trial
Information 501; Error Reporting: (xxxv) Unsuccessful Dispensing Attempts
History 502,
(xxxvi) Error Codes History 504; Alerts Information: (xxxvii) Alerts Selection
and Timing 506,
(xxxviii) Prescriber's Name 508, (xxxix) Prescriber's Email 510, (xl)
Prescriber's Texting
Telephone No. 512, (xli) Disease Manager's Name 514, (xlii) Disease Manager
Email 516,
(xliii) Disease Manager Telephone Texting No. 518, (xliv) Relative No. 1 Name
520, (xlv)
Relative No. 1 Email 522, (xlvi) Relative No. 1 Telephone Texting No. 524,
(xlvii) Relative No.
2 Name 526, (xlviii) Relative No. 2 Email 528, xlix) Relative No. 2 Telephone
Texting No. 530,
(1) Relative No. 3 Name 532, (1i) Relative No. 3 Email 534, (lii) Relative No.
3 Telephone
Texting No. 536.
[000232] The Patient Reporting 226 module encompasses, as an example: (i)
the ability of
the Patient 6 to request certain reports generated by the Opioid Specific App
12, e.g., the last
time the Patient 6 took the opioid, prescription information details, opioid
details (e.g., brand and
generics names, batch number, expiration/beyond-use date, doses remaining,
reorder
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information, drug interactions, typical side effects, etc.); (ii) graphs and
charts created by the
Opioid Specific App 12 based upon Interface Device 14 or Standalone Drug
Dispenser 16 stored
information; and (iii) graphs, charts and/or reports created by the Integrated
Support Center's 22
Data Servers 10 for downloading by the Patient 6 via the Opioid Specific App
12, etc.
[000233] The Drug Cassette Replacement 227 module is designed to use the
Patient Identifier
Number 160 and the drugs NDC 70 number to preclude the Patient 6 from
dispensing duplicate
doses for the same opioid from one or more Prescriptions 4 prescribed by one
or more
Prescribers 2 and/or dispensing the opioid 70 prescribed dose from one or more
Drug Dispensers
16 or Drug Cassettes 18 containing the specified drug 70 (to eliminate
duplicate dosing). The
program accompanies this by prioritizing Disposable Drug Dispensers 16 with an
integrated drug
cassette and/or Drug Cassettes 18 containing the same opioid 70 so the opioid
70 in a given
Disposable Drug Dispenser 16 and/or Drug Cassette 18: (i) must be fully
dispensed per the
Prescription 4 before a subsequent Drug Cassette 18 can begin dispensing the
given drug 70, or
(ii) the first Disposable Drug Dispenser 16 or Drug Cassette 18 is designated
as locked
(precluded from dispensing) and a subsequent Disposable Drug Dispenser 16 or
Drug Cassette
18 is enabled to dispense the single opioid dose in keeping with the
Prescription 4. This enables
dispensing from multiple Disposable Drug Dispensers 16 containing the same
drug in the event a
Disposable Drug Dispenser 16 is inoperable, lost, or left at another location.
This also enables
the utilization of multiple Drug Cassettes 18 (for Reusable Drug Dispensers
16) in the event a
problem arises with a particular Drug Cassette 18 (e.g., it is damaged,
improperly stored, the
original reusable Drug Dispenser 16 is lost or damaged, etc.). This process
affords the Prescriber
2 and Pharmacy 8 the ability to dispense sufficient opioid doses to limit the
number of Pharmacy
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8 visits and/or mail order shipments between refills (within state/government
prescribing
guidelines).
[000234] The Package Insert 228 module pulls the respective opioid's
package insert in the
appropriate language (as designated by the Patient's 6 language preference)
from the Drug
Package Insert Database on the Data Servers 10 and incorporates it into the
Opioid Specific App
12.
[000235] The Dispenser Manual 230 module pulls the respective Drug
Dispenser 16 manual
in the appropriate language from the Drug Dispenser Manual Database on the
Data Servers 10
and incorporates it into the Opioid Specific App 12.
[000236] The App Manual 232 module pulls the respective Opioid Specific App
12 manual
in the appropriate language from the Opioid Specific App Manual Database on
the Data Servers
and incorporates it into the Opioid Specific App 12. The App manual program
logic enables
the system to download a personalized Patient 6 specific manual that
incorporates the Drug
Specific Dispensing Algorithm 13 and Prescriber 2 prescribed 4 and defined
digital capture, self-
assessment, self-testing, and self-reporting data capture and screen
instructions and their
respective troubleshooting instructions.
[000237] The Help and Troubleshooting 234 module is an artificial
intelligence based query
based module that allows the Patient 6 to enter key words or phrases to bring
up a list of
potential sections that may address the Patient's 6 issue. Sections applicable
to a specific help
and troubleshooting screen on the Interface Device 14 or Standalone Drug
Dispenser 16 on the
Opioid Specific App 12 are hotlinked to allow instructions to be viewed
without interrupting the
Patient 6 input dispensing sequence. The base module answers most questions.
However, a link
to an expanded version of Help and Troubleshooting hosted on the Central
Servers 10 is
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provided in each screen. The Central Servers 10 also host a User Group to
allow Patient's 6 to
ask questions of other users as well as to post recommended improvements
and/or enhancements
to the Opioid Specific App 12 and/or the respective Drug Dispensers 16 and/or
support services,
etc. Links are also provided to video tutorials on video sharing websites
(e.g., YouTube, Vimeo,
etc.).
[000238] The Training Module 236 encompasses, as an example, (i) a hot link
to the
Dispenser Manual 230 and the App Manual 232 as well as a training and
troubleshooting video
library resident on the Training Videos Database resident on the Data Servers
10; (ii) videos
posted, as an example, on YouTube, Vimeo, and/or other consumer video services
covering all
aspects of utilizing and troubleshooting the Opioid Specific App 12 and the
respective Drug
Dispensers 16, (iii) a step by step tutorial resident on the Interface Device
14, (iv) a hot linked
"help" button on each respective screen allowing the Patient 6 to bring up
usage instructions for
the respective screen without interrupting the sequence of entering the
required information or
selecting a particular command, etc.
[000239] A similar medical professional training module is available to
assist the medical
professional/Prescriber 2/Pharmacy 8 in all issues related to each respective
Drug Dispenser 16,
Drug Cassettes 18 and to troubleshoot documentation or software issues. These
files and Videos,
resident on the Central Servers 10, would be accessible, as an example, on
popular video sharing
websites (e.g., YouTube, Vimeo, etc.).
[000240] The Unique App Serial Number 238 is assigned by the App Generation
Program
when it is ready to finalize the aggregation of the Personalized Opioid
Specific App 240.
[000241] The Personalized Opioid Specific App 240 is then linked to the
Patient Identifier
No. 160. Then the Patient Specific Opioid Specific App 12 is: (i) compiled;
stored in the Opioid
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Specific App Database on the Data Servers 10, and (iii) is automatically
transmitted to the
Patient 6 in a download Email and/or text message. The Patient 6 clicks on the
link on the Email
or text message or pastes the link in the browser to be taken to the download
screen where the
Patient 6 clicks on the Download App 246 to download the Opioid Specific App
12.
[000242] The Patient Identifier No. 160 links the Patient 6 with the
Patient Specific Opioid
Specific App 12. The Patient Identifier No. 160 is utilized by the Patient 6
when accessing the
Opioid Specific App 12 for the first time to set up the Biometric Login 250.
[000243] The Opioid Specific App 12 utilizes, for example, the Interface
Device's 14
features, memory and computer power to; (i) facilitate the Opioid Specific
App's 12 interface
with the Patient 6, (ii) uses the Interface Device's 14 Bluetooth and/or Wi-Fi
communications
capability to interface with the Drug Dispenser 16, (iii) its Internet
communications capability to
interface with the Data Center 10 and the Integrated Support Center 22, (iv)
uses its Email and
texting capabilities to send alerts to the Patient 6, the Prescriber 2, 508
other caregivers, the
Patients 6 disease manager 514, and/or family members 520, 526, 532, (v) the
phone to call the
Integrated Support Center 22, (vi) the video player capabilities to play user
instruction,
troubleshooting, drug and disease information videos, (vii) its GPS capability
if location is
required for the capture of lifestyle information, (viii) the Interface
Device's 14 memory to store
the Opioid Specific App 12, the Prescription 4, dispensing history 464, tamper
alert history 448
(etc.), and most recent Patient 6 entered information and screen responses
494, 496, 498, 499,
500, 501 as well as digitally captured information 492 which was used to make
a dispensing
decision by the Drug Specific Dispensing Algorithm 13 or which was requested
to be captured
for future utilization by the Prescriber 2 or other medical professionals 108,
110, (ix) its voice
recognition and communication capabilities, etc.
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[000244] Utilization of an Interface Device 14 allows the Drug Dispenser 16
to: (i) be smaller
than it would otherwise be; (ii) cost less to manufacture; (iii) decreases
battery power
requirements, etc. These same or a combination of the afore listed
capabilities are incorporated
into the Disposable Drug Dispensers 16 as well as the Standalone Drug
Dispensers 16.
[000245] FIG. 6 is an exemplary embodiment of the Biometric Authentication
interface
which is designed to be compliant with the Health Insurance Portability and
Accountability Act
(HIPAA) or any governmental body that sets the standard for protecting
sensitive patient data.
This means that all the required physical, network, and process security
measures are in place
and followed and incorporated herein by reference.
[000246] When the Patient 6 clicks on the Opioid Specific App 12 the first
time, it brings up
the Set Up Biometric Logon 250 screen. It asks the Patient 6 to enter the
Patient Identifier
Number 160 previously sent to the Patient 6, via Email or Text, into the
Patient Identification
No. 252 input box. It then establishes if the Patient's 6 language preference
253 and allows the
Patient 6 to choose, if preferred, the Opioid Specific App's 12 voice
interface preference 253. It
then requests the: (i) Patient's Full Name 254, (ii) Patient's Street Address
256, (iii) Patient's
Telephone No. 258 (this is the require mobile phone/Interface Device 14 or
Standalone Drug
Dispenser 16 telephone number), and (iv) Patient's Email Address 260 (this
will accommodate
one or more Email addresses). Thereafter it goes into the routines to capture
the biometric
authentication reference information for one or more of the following: (v)
Fingerprint Scan 262,
(vi) Face Scan 264, (vii) Iris Scan 266, (viii) Voice Print 268, (ix) Tech
Support Password 270,
(x) Tech Support Challenge Question 1 272, (x) Tech Support Challenge Question
2 274. Once
the Biometric login is established 276, the Opioid Specific App 12 saves the
Biometric Logon
information in the Logon Data Repository 445 repository in the Interface
Database 278. At that
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point, the Opioid Specific App 12 is ready to begin authorizing the Drug
Dispenser 16 to
dispense medication.
[000247] Thereafter, when the Patient 6 clicks on the Opioid Specific App
12 or clicks on the
Reminder Screen 250, the Biometric Logon 280 screen appears. If the Biometric
Logon 280 is
not successful, No 282, then the Patient 6 is asked to try again. After a
designated number of
tries, the Patient 6 is given troubleshooting instructions. The
troubleshooting instruction contains
a single click call button to connect the Patient 6 with the Integrated Call
Center 22. If the
Biometric Logon 280 is successful, Yes 284, then the Opioid Specific App 12
automatically tries
to handshake with all designated digital monitoring devices 286. If
successful, Yes 292, the
Opioid Specific App 12 downloads the designated information into the Interface
Database 278.
If the digital handshake 286 is not successful, No 288, then the Opioid
Specific App 12 retries to
effectuate the handshake. If it is not able to effectuate the handshake after
a specified number of
tries, it stops trying and sends and alert message 290 and then proceeds to
try to effectuate a
handshake 302 with the Drug Dispenser 16. If the Biometric Logon 280 is
successful, Yes 284,
simultaneous to trying to handshake with digital devices 286, the routine
tries to handshake with
the Drug Dispenser 302. If it is successful, Yes 304, then the unit is ready
to go through the
Drug Specific Dispensing Algorithm 13 screens to allow the Drug Dispenser 16
to dispense an
opioid dose. If the handshake with the drug dispenser is not successful, No
294 or No 296, then
the routine will attempt two more times to effectuate the handshake. If the
third (3rd) try t is not
successful, No 298, the routine shows an Unsuccessful Handshake Instructions
300 screen telling
the Patient 6 how to resolve the problem.
[000248] FIG. 7 is an exemplary embodiment of logic flow and process
related to loading an
opioid Drug Cassette 18 into a Reusable Drug Dispenser 16. This process is not
applicable for
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tamper proof Disposable Drug Dispensers 16 which contain an integrated Drug
Cassette 18 and
cannot be opened after the Drug Cassette 18 is loaded into the then sealed
Disposable Drug
Dispenser 16. The following description is an exemplary of how a restricted
opioid Drug
Cassette 18 would be loaded into the Reusable Drug Dispenser 16 by a medical
professional. (A
similar but less restrictive routine can be followed by the Patient 6 to load
a Drug Cassette 18
into a Reusable Drug Dispenser 16 for medications where diversion, addiction,
dependence,
abuse, misuse, etc. are not of concern.)
[000249] To load the Drug Cassette 18, the Medical Professional opens
his/her ePrescription
4 screen for the Prescribed 4 medication and thereafter plugs in a USB Cable
from the Rx
Computer into the Drug Dispenser 16. Alternatively, a USB Cable can be plugged
in from a
Computer with the requisite software to enable the entry of the requisite
codes needed to open
the Drug Dispenser 16.
[000250] The USB cable provides power to the Drug Dispenser's independent
clamshell
locking and unlocking mechanism 1028, 1030. Power for the clamshell locking
and unlocking
mechanism 1028, 1030 is not available from the Drug Dispenser's 16 battery.
[000251] After the program confirms that the Dispenser Identification No.
158 assigned to
the medication is the same as, corresponds with, the Dispenser Identification
No. 158 contained
in the Drug Dispenser's Firmware 352, the Drug Dispenser 16 may be opened to
allow loading
of the Drug Cassette 18. If the Dispenser Identification No. 158 is blank on
the Drug
Dispenser's 16 firmware because this is the first time the Drug Dispenser 16
is being utilized for
that medication, then the program inserts the Dispenser Identification No. 158
into the Drug
Dispenser's Firmware 352.
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[000252] The Dispenser Identification No. 158 cannot be copied into the
Opioid Specific
App's 12 Interface Database 278. It is copied and retained in the Dispenser
Opening Codes 446
data repository resident on the Patient Database 152 stored in the Data
Servers 10.
[000253] The USB cable is the same cable that is used to charge the battery
in rechargeable
battery configuration Reusable Drug Dispensers 16.
[000254] If the Dispenser Identification No. 158 is the same as the code in
the Dispenser
Firmware 352, then the program proceeds to effectuate a handshake with the
Drug Dispenser 316
and proceeds to try to Open the Drug Dispenser 318. If it cannot open the drug
dispenser, No
320, then the program restarts the dispenser opening routine 310. Prior to
unlocking the
Reusable Drug Dispenser 16, the program checks to see if there is sufficient
battery power 323.
If the answer is No 324, then the program requires that the battery be changed
or the unit be
recharged 326 to a minimum level prior to allowing the Drug Cassette 18 to be
loaded 330 into
the Reusable Drug Dispenser 16.
[000255] The temperature within the Drug Cassette 18 cavity within the Drug
Dispenser 16 is
monitored during recharging to ensure it does not exceed the allowable
medication storage
temperature 104. If the temperature 104 is within, for example, one degree of
the maximum
storage temperature 104, the recharge is stopped until the temperature within
the Drug Cassette
18 storage cavity is back to the acceptable recharge temperature range before
charging.
[000256] If there is sufficient battery power or if the battery power has
been restored to a
sufficient battery power level, Yes 328, then the Drug Cassette 18 can be
loaded 330 into the
Reusable Drug Dispenser 16. If this is the initial drug cassette 332 for this
medication, Yes 334,
then the program updates the drug information on the drug dispenser's firmware
336. If this is a
not the initial Drug Cassette 18 docking, No 338, for the medication, then the
program confirms
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that the correct drug per the Prescription 4 is in the drug cassette 340 by
comparing the
prescribed drug in the Prescription 4 versus the drug indicated in the
firmware 352. If it is not
the correct drug, No 342, then the program provides the troubleshooting
instructions 344. If it is
the correct drug in the drug cassette, Yes 346, then the program copies the
Drug Cassette Serial
No. 348 and links it with the Drug Dispenser Serial No. 350 on the Opioid
Specific App 12
resident on the Interface Database 278. It then proceeds to synchronize: (i)
the appropriate time
and date 354, (ii) drug expiration date 356, (iii) proper storage temperature
range 358, (iv)
acceptable humidity range 360, (v) the number of pills available 362, and then
(vi) clear the
dispensing history on the firmware 364 for all values but the last dispensing
date and time, and
(vii) clear the firmware tamper sensor history 366, and (viii) ensure the same
data is contained on
both the Drug Dispenser 16 firmware 352 and the Opioid Specific App 12
Interface Database
278. At this point, the Drug Cassette's 18 and the Drug Dispenser's 16 serial
numbers are linked
together 370 on the Opioid Specific App 12. At that point, the Opioid Specific
App 12 data is
synchronized 372 with the Patient Database 152 on the Data Servers 10. If
immediate
synchronization cannot be effectuated, the program stores the information for
synchronization
the next time a connection is available.
[000257] FIG. 8 is an exemplary embodiment depicting data synchronization
and updating
between the three Opioid Specific App 12 related databases, (i) Patient
Database 152 which is
resident on the centralized Data Servers 10, (ii) the Dispenser Database 380
that is part of the
Opioid Specific App 12 that is resident on the Interface Device 14 or on the
Standalone Drug
Dispenser 16, and (iii) the Dispenser Firmware 352 in each Drug Dispenser 16.
[000258] When the Drug Cassette 18 is finished being loaded into the
Reusable Drug
Dispenser 16, a handshake is effectuated between the Drug Dispenser 16 and the
Opioid Specific
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App 12. Upon recognizing that there is a new Drug Cassette 18, the Opioid
Specific App 12
links with the Patient Database 152 and begins a data update process to ensure
the respective
data is synchronized and the most current. First the program synchronizes and
updates the
Dispenser Database 380 data 382, 384, 386, 388, 390, 392 and effectuates any
updates 394 from
the Dispenser Database 380 to the Patient Database 152. Then the update
program 394 proceeds
to utilize the Patient Database 152 to synchronize and update the Dispenser
Firmware 352, 396,
398, 400, 402, 404, 406, 408, 410, 412, 414, 416, 418, 420, 422, 158, 160,
424, and 426. Any
changes which are more current on the Dispenser Firmware 352 are updated on
the Patient
Database 152. This sequence is repeated every time that the patient dispenses
a dose, or if the
Internet connection is not available, as soon as an Internet connection is
established between the
Interface Device 14 or the Wi-fl enabled Standalone Drug Dispenser 16 and the
Data Servers 10.
[000259] FIG. 9 is an exemplary embodiment of the database files which are
synchronized
when the Sync Data 430 routine for the Patient Database 152 is initiated: 202,
204, 206, 208,
210, 212, 214, 216, 218, 220, 222, 224, 226, 228, 230, 232, 234, 236, 238.
Once they are
synchronized, then the Personalized Opioid Specific App 12 is fully updated
and Ready To
Dispense 432.
[000260] FIG. 10 is an exemplary embodiment of the Interface Database 278
types of data
and data files/databases which are continually synchronized with the Patient
Database 152. The
Opioid Specific App 12 data contained in the Interface Device Database 278 is
synchronized real
time with the centralized Patient Database 152. The Interface Database 278
retains information
for a defined time period to enable the Drug Specific Dispensing Algorithm 13
and/or the App's
Prescribed 4 Patient 6 values and side effects reporting routines to use and
present trended data
while minimizing the Drug Dispenser 16 and the Opioid Specific App's 12 memory
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requirements. The Patient Database 152 resident on the Data Servers 10 retains
an ongoing
history without deleting prior patient data.
[000261] The following is a representation of the types of data files which
are synchronized:
Patient Information: (i) Patient's Full Name 440, (ii) Patient's Street
Address 442, (iii) Patient's
Date of Birth 444; (iv) Logon Data Repository 445; Dispenser Information: (v)
Dispenser
Opening Codes 446 (accommodates more than one dispenser code), (vi) Tamper
Attempt
History 448, (vii) Dispenser Serial No. 450 (accommodates more than one
dispenser serial
number), (viii) Drug Cassette Serial No. 452 (accommodates more than one
cassette serial
number), (ix) Drug NDC No. 454, (x) Drug Batch No. 456, (xi) Drug Expiration
Date 458
(retains one expiration date per drug batch), (xii) Drug Storage Temperature
460, (xiii) Drug
Storage Humidity 462, (xiv) Last Dose Time and Date 464, (xv) Number of Pills
Remaining
466; Prescription Information: (xvi) Drug Name 468, (xvii) Strength 470,
(xviii) Dosage Form
472, (xix) Prescribed Drug Quantity 474, (xx) Refills Authorized 476, (xxi)
Prescriber's Full
Name 478, (xxii) Prescriber's National Provider ID (NPI) 480, (xxiii)
Prescriber's DEA No. 482,
(xxiv) Store (Pharmacy) Name 484, (xxv) Prescription Reference No. 486, (xxvi)
Prescription
Issuance Date 488; Values Tracking: (xxvii) Prescription (Dosing Schedule)
490, (xxviii)
Digitally Tracked Values13 492, (xxix) Self-Assessment Values 494, (xxx) Self-
Test Values 496,
(xxxi) Self-Reported Values 498, (xxxii) Concomitant Medications 499, (xxxiii)
Side Effect
Values 500, (xxxiv) Clinical Trial Information 501; Error Reporting: (xxxv)
Unsuccessful
Dispensing Attempts History 502, (xxxvi) Error Codes History 504; Alerts
Information: (xxxvii)
Alerts Selection and Timing 506, (xxxviii) Prescriber's Name 508, (xxxix)
Prescriber's Email
510, (xl) Prescriber's Texting Telephone No. 512, (xli) Disease Manager's Name
514, (xlii)
13 The patient values require that the database is able to accommodate capture
data from the
respective number of digital devices tracked as well as for the number data
capture screens used.
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Disease Manager Email 516, (xliii) Disease Manager Texting Telephone No. 518,
(xliv) Relative
No. 1 Name 520, (xlv) Relative No. 1 Email 522, (xlvi) Relative No. 1 Texting
Telephone No.
524, (xlvii) Relative No. 2 Name 526, (xlviii) Relative No. 2 Email 528, xlix)
Relative No. 2
Texting Telephone No. 530, (1) Relative No. 3 Name 532, (1i) Relative No. 3
Email 534, (lii)
Relative No. 3 Texting Telephone No. 536.
[000262] FIG. 11 is an exemplary embodiment of the Opioid Specific App 12
logic. When
the Patient 6 starts the Opioid Specific App 540 by either clicking on the App
or by responding
to the dose due alert, the screen automatically moves to the Biometric Logon
250 screen. Upon
successful biometric authentication, the program checks to see if the product
has expired 542, if
Yes 544, it presents a product expiration patient screen notification 552, and
if a refill is
authorized, automatically sends a refill request to the pharmacy 554.
Simultaneously, the
program locks the drug dispenser 546, updates the patient database 548, and
notifies the
Integrated Call Center 550. If the product has not expired, No 556, then it
proceeds to check to
see if the product has been stored in the correct storage temperature 558
since the product was
last dispensed.
[000263] If the medication has not been stored at the correct storage
temperature, No 560, it
presents an incorrect storage temperature patient screen notification 562, and
if a refill is
authorized, automatically sends a refill request to the pharmacy 554.
Simultaneously, the
program locks the drug dispenser 546, updates the patient database 548, and
notifies the
Integrated Call Center 550. If the product has been stored at the correct
storage temperature, Yes
564, then it proceeds to check to see if the product has been stored in the
correct humidity range
566 since the product was last dispensed.
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[000264] If the medication has not been stored at the correct humidity
level, No 568, it
presents an incorrect storage humidity patient screen notification 570, and if
a refill is authorized,
automatically sends a refill request to the pharmacy 554. Simultaneously, the
program locks the
drug dispenser 546, updates the patient database 548, and notifies the
Integrated Call Center 550.
If the product has been stored at the correct storage humidity, Yes 572, then
it proceeds to check
the last dose time and date and dispensing history 574 to establish the basis
for checking the
requisite information required to authorize dispensing.
[000265] FIG. 12 is an exemplary embodiment of the prescription information
the program
checks prior to authorizing dispensing of a medication dose. The program sees
if the prescribing
request is within the Prescription's 4 time between doses 580 instructions, if
No 581, the
program issues a patient alert 582 indicating when the next dose will be
available. If the time
interval is within the prescribing guidelines, Yes 583, then the program
checks to see if the
maximum daily doses 584 have been exceeded. If the maximum number of daily
doses have
been exceeded, Yes 585, the program issues a patient alert 586 stating that
the request exceeds
the prescribed maximum number of daily doses and indicates when the next dose
will be
available. If the maximum number of daily doses has not been exceeded, No 587,
the program
checks to see if the maximum authorized dosing days 588, i.e., the number of
days the
prescription is in effect, have been exceeded. If Yes 590, a patient alert 592
is issued stating the
prescription period has expired and instructing the Patient 6 to contact the
Prescriber 2 if he/she
has any questions. If the maximum number of authorized dosing days has not
been exceeded,
No 594, the program has ascertained that it is authorized to dispense 596 by
the Prescription 4
and proceeds to aggregate digitally captured Patient 6 information.
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[000266] FIG. 13 is an exemplary embodiment of the program routines to
aggregate digitally
captured information from third party devices via application program
interfaces, APIs. As an
example, the information may be aggregated from the Patient's 6 smartphone
(e.g., diet diaries,
stress, oxygen saturation, heart rate, other medications taken, and Bluetooth
connected drug
dispenser information, etc.), wearable monitors (e.g., smart watch, exercise
monitor, holter
monitor, ECG, RFID chip tracker, wearable diagnostic monitor, etc.), external
monitoring and
diagnostic devices (e.g., scales, diagnostic devices, clothing, pill
dispensers, etc.), connectivity
bridges and connectivity hugs (e.g., Verily's Connectivity Bridge), and RFID
chips whose API
interface allows the signal to be picked up and the data stored on the Opioid
Specific App's 12
Interface Database 278, and subsequently on the Patient Database 152 on the
Data Servers 10,
etc.
[000267] Each tracked interface has its own API. The program is organized
to aggregate the
data on a sequential basis, e.g., it goes through all the Smartphone App APIs
(more than one may
be designated) before it goes to the Wearable Monitor APIs (more than one may
be designated)
and so forth.
[000268] The program begins gathering digitally captured Patient 6
information by accessing
the respective Smartphone App API(s) 600 to access and aggregate the
designated information,
access the data 602. If it is successful in accessing the data, Yes 604, the
program accesses the
Interface Database 278 and enters the values in the Digitally Tracked Values
Database 492. If it
is unable to access the data, No 606, then it creates an error report 608,
creates and sends a
patient advisory correction steps 610 email to the Patient 6, accesses the
Interface Database 278
and enters the Error Report 608 into the Error Code History 504 database. It
then continues to
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the next Smartphone App API, or if no more are indicated, to the Wearable
Monitor(s) API(s)
612.
[000269] It accesses the Wearable Monitor API(s) 612 to access and
aggregate the designated
information and then accesses the data 614. If it is successful in accessing
the data, Yes 616, the
program accesses the Interface Database 278 and enters the values in the
Digitally Tracked
Values Database 492. If it is unable to access the data, No 618, then it
creates an error report
620, creates and sends a patient advisory correction steps 622 email to the
Patient 6, accesses the
Interface Database 278 and enters the Error Report 620 into the Error Code
History 504
database. It then continues to the next Wearable Monitor API, or if no more
are indicated, to the
External Monitor(s) API(s) 624.
[000270] It accesses the External Monitor API(s) 624 to access and
aggregate the designated
information and then accesses the data 626. If it is successful in accessing
the data, Yes 627, the
program accesses the Interface Database 278 and enters the values in the
Digitally Tracked
Values Database 492. If it is unable to access the data, No 628, then it
creates an error report
630, creates and sends a patient advisory correction steps 632 email to the
Patient 6, accesses the
Interface Database 278 and enters the Error Report 630 into the Error Code
History 504
database. It then continues to the next External Monitor API, or if no more
are indicated, to the
RFID Chip API(s) 634.
[000271] It accesses the RFID Chip API(s) 634 to access and aggregate the
designated
information and then accesses the data 636. If it is successful in accessing
the data, Yes 637, the
program accesses the Interface Database 278 and enters the values in the
Digitally Tracked
Values Database 492. If it is unable to access the data, No 638, then it
creates an error report
640, creates and sends a patient advisory correction steps 642 email to the
Patient 6, accesses the
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Interface Database 278 and enters the Error Report 640 into the Error Code
History 504
database. It then continues to the next External Monitor API, or if no more
are indicated, to the
Patient Self-Assessment Input Screen 624.
[000272] FIG. 14 is an exemplary embodiment of the program to capture
patient self-
assessment, patient self-test, and/or patient self-reported physiological,
psychological, lifestyle,
medications taken since the last opioid dose and/or concomitant medications
taken, and/or
environmental information/values through designated Patient 6 input screens on
the Opioid
Specific App 12. The data may be required by: (i) the Drug Specific Dispensing
Algorithm 13, or
(ii) as designated by the Prescriber 2 when he/she filled out the Prescription
4, or (iii) as required
by regulatory agencies for the drug's regulatory approval if the product is in
clinical trials. The
number of screens presented versus the value of the collected data must be
carefully weighed. A
specific data screen may be presented each time the Patient 6 wants to
dispense a dose or it may
be presented on a predefined schedule or in response to a digitally captured
value or a Patient 6
entered value/information.
[000273] The program is organized to aggregate the data on a sequential
basis, e.g., it goes
through all the patient self-assessment screens (more than one may be
designated) before going
to the patient self-test screens (more than one may be designated) and then to
the patient self-
report screens (more than one may be designated). The following represents
examples of the
data gathering logic for each.
[000274] After completing the RFID Chip API(s) routine, the program
proceeds to the Patient
Self-Assessment Input 650 screen. Before presenting the designated screen, it
checks the request
schedule 652. If the screen is designated, then it presents the screen and
requests the patient
input 654. If the Patient 6 is able to input his/her information, Yes 656, the
program accesses the
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Interface Database 278 and enters the values in the Self-Assessment Values
Database 494. If it
is unable to capture the information, No 658, then it creates an error report
660, accesses the
Interface Database 278, and enters the error code in the Error Code History
504 file.
Simultaneously, it creates and presents patient instructions 662 on the
Interface Device 14 or
Standalone Drug Dispenser 16 interface screen and prompts the Patient 6 to
begin the patient
input process again. Once the values have been added to the Self-Assessment
Values Database
494, the program proceeds to the next designated patient self-assessment
routine, and if no more
are called for, it proceeds to the Patient Self-Test Input Screen 664 routine.
[000275] Before presenting the designated Patient Self-Test Input Screen
664, the program
routine checks the request schedule 666. If the screen is designated, then it
presents the screen
and requests the patient input 668. If the Patient 6 is able to input his/her
information, Yes 670,
the program accesses the Interface Database 278 and enters the values in the
Self-Test Values
Database 496. If it is unable to capture the information, No 672, then it
creates an error report
674, accesses the Interface Database 278, and enters the error code in the
Error Code History 504
file. Simultaneously, it creates and presents patient instructions 678 on the
Interface Device 14
or Standalone Drug Dispenser 16 interface screen and prompts the Patient 6 to
begin the patient
input process again. Once the values have been added to the Self-Test Values
Database 494, the
program proceeds to the next designated patient self-test routine, and if no
more are called for, it
proceeds to the Patient Self-Report Input Screen 680 routine.
[000276] Before presenting the designated Patient Self-Report Input Screen
680, the program
routine checks the request schedule 682. If the screen is designated, then it
presents the screen
and requests the patient input 684. If the Patient 6 is able to input his/her
information, Yes 686,
the program accesses the Interface Database 278 and enters the values in the
Self-Reported
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Values Database 498. If it is unable to capture the information, No 688, then
it creates an error
report 690, accesses the Interface Database 278, and enters the error code in
the Error Code
History 504 file. Simultaneously, it creates and presents patient instructions
692 on the Interface
Device 14 or Standalone Drug Dispenser 16 interface screen and prompts the
Patient 6 to begin
the patient input process again. Once the values have been added to the Self-
Reported Values
Database 498, the program proceeds to the next designated patient self-
reported routine, and if
no more are called for, it proceeds to the Patient Concomitant Medications
Input Screen 700
routine.
[000277] FIG. 15 is an exemplary embodiment of the program to capture
patient concomitant
medications, side effects, and/or patient reported clinical trial information
on the designated
Opioid Specific App 12 data capture screens required by: (i) the Drug Specific
Dispensing
Algorithm 13, and/or (ii) as designated by the Prescriber 2 when he/she filled
out the Prescription
4, and/or (iii) as required by regulatory agencies for the drug's regulatory
approval if the product
is in clinical trials. The number of screens presented versus the value of the
collected data must
be carefully weighed. A specific data screen may be presented each time the
Patient 6 wants to
dispense a dose or it may be presented on a predefined schedule or in response
to a digitally
captured value or a Patient 6 entered value/information.
[000278] The program is organized to aggregate the data on a sequential
basis, e.g., it goes
through, for example, the Patient Concomitant Medications Input Screen(s) 700,
then the Side
Effects Tracking 712 screen(s), and then the Patient Reported Clinical Trial
Data 724 screen(s).
The following represents examples of the data gathering logic for each.
[000279] Upon completion of the patient self-assessment, and/or the patient
self-test, and/or
the patient self-reported input screens, the program presents the Patient
Concomitant
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Medications Input Screen 700 and requests the patient input 702. If the
Patient 6 is able to input
his/her information, Yes 704, the program accesses the Interface Database 278
and enters the
values in the Concomitant Medications Database 499. If it is unable to capture
the information,
No 706, then it creates an error report 708, accesses the Interface Database
278, and enters the
error code in the Error Code History 504 file. Simultaneously, it creates and
presents patient
instructions 710 on the Interface Device 14 or Standalone Drug Dispenser 16
interface screen
and prompts the Patient 6 to begin the patient input process again. Once the
values have been
added to the Self-Reported Values Database 499, the program proceeds to the
Side Effects
Tracking Per Prescriber's Request 712 input routine.
[000280] The program presents the Side Effects Tracking Per Prescriber's
Request 712 input
screen and requests the patient input 714. If the Patient 6 is able to input
his/her information,
Yes 716, the program accesses the Interface Database 278 and enters the values
in the Side
Effects Tracking Database 500. If it is unable to capture the information, No
718, then it creates
an error report 720, accesses the Interface Database 278, and enters the error
code in the Error
Code History 504 file. Simultaneously, it creates and presents patient
instructions 722 on the
Interface Device 14 or Standalone Drug Dispenser 16 interface screen and
prompts the Patient 6
to begin the patient input process again. Once the values have been added to
the Side Effects
Tracking Database 500, the program proceeds to the Patient Reported Clinical
Trial Information
724 input routine.
[000281] The program presents the Patient Reported Clinical Trial
Information 724 input
screen and requests the patient input 726. If the Patient 6 is able to input
his/her information,
Yes 728, the program accesses the Interface Database 278 and enters the values
in the Clinical
Trial Information Database 501. If it is unable to capture the information, No
730, then it creates
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an error report 732, accesses the Interface Database 278, and enters the error
code in the Error
Code History 504 file. Simultaneously, it creates and presents patient
instructions 734 on the
Interface Device 14 or Standalone Drug Dispenser 16 interface screen and
prompts the Patient 6
to begin the patient input process again. Once the values have been added to
the Clinical Trial
Information Database 501, the program proceeds to the Dispensing Algorithm 740
routine.
[000282] FIG. 16 is an exemplary embodiment of the logic followed by the
Dispensing
Algorithm 740. Any information requested by the prescriber or aggregated for
use for clinical
trial data capture that is not required by the Drug Specific Dispensing
Algorithm 13 is not taken
into account when making dispensing decisions. The algorithm sequentially
cycles through the
digitally captured values to the patient inputted data to the concomitant
medications information
to make a dispensing decision.
[000283] The Dispensing Algorithm's 740 program begins by checking each of
the digitally
captured values to see if they are in range 742. The routine cycles through
each of the selected
values 744 to ascertain if they are within the predefined acceptable range
746. If the answer is
No 748 for any value, then the program locks the Drug Dispenser 546, issues a
patient alert 750
to the Patient 6 and anyone else who is listed as an individual that should be
alerted, advises the
Integrated Call Center 752, and updates the unsuccessful dispensing attempts
history 502. If all
the digitally captured values are within the acceptable range(s), Yes 756,
then the program
proceeds to check the patient inputted data.
[000284] The program checks the respective Patient 6 self-assessment, self-
test, and self-
reported input data to ascertain if the data is acceptable 758, then cycles
through each selected
input 760 to ascertain if they are within the predefined acceptable range 762.
If the answer is No
764 for any value, then the program locks the Drug Dispenser 546, issues a
patient alert 766 to
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the Patient 6 and anyone else who is listed as an individual that should be
alerted, advises the
Integrated Call Center 768, and updates the unsuccessful dispensing attempts
history 502. If all
the self-assessment, self-test, and self-reported values are within the
acceptable range(s), Yes
772, then the program proceeds to check the concomitant medications diary.
[000285] The logic then checks the new concomitant medications list 774 and
cycles through
each selected medication 776 to ascertain if there is a potential interaction
778 that could result
in an adverse drug-drug mediated adverse event. If the answer is No 780 for
each new
medication, then the program is ready to dispense 782, brings up a ready to
dispense notification
786 on the Interface Device's 14 or the Standalone Drug Dispenser's 16 screen,
and then
proceeds to synchronize the Interface and Patient Databases 788 to indicate
the dispensing of the
medication dose was authorized at a specific date and time (The program
automatically makes
adjustments for time travel differences for patients who travel). This
information along with the
date and time the Drug Dispenser 16 dispenses the dose can be used to
ascertain if there may be
possible medication diversion.). However, if a potential drug-drug interaction
is flagged, Yes
790, then the program locks the Drug Dispenser 546, issues a patient alert 792
to the Patient 6
and anyone else who is listed as an individual that should be alerted, advises
the Integrated Call
Center 794, and updates the unsuccessful dispensing attempts history 502.
[000286] FIG. 17 is an exemplary embodiment of the Integrated Support
Center 22 triage
flow from Patient 6 contact through issue resolution. Triage is organized into
three main types
of Patient 6 support calls: dispenser operation, dosing issues, and medical
questions.
[000287] Each of the patient alerts 290, 552, 562, 570, 582, 586, 592, 610,
622, 632, 642,
662, 678, 692, 710, 722, 734, 750, 766, 792, etc. presented on the Interface
Device 14 or
Standalone Drug Dispenser 16, contain an automatic dialing option to
immediately contact the
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Integrated Call Center 22 to resolve the dispensing issue(s). The email and
text message alerts
contain clearly denoted Integrated Call Center 22 call numbers.
[000288] When the Patient 6 calls 14 the Integrated Call Center 22 the call
center's security
program brings up the patient identification verification routine 800. If the
Integrated Call
Center does not initially identify the Patient 6, No 802, it has alternatives
available to verify the
Patient's 6 identity within the HIPPA Privacy Rules for protection of the
individuals' medical
records and other personal health information.
[000289] Once the Patient's 6 identification is verified, Yes 804, the call
center representative
looks at the Patient's 6 profile generated by the call center software that
draws the Patient 6
information from the Patient Database 152 resident on the Data Servers 10 to
assist in triaging
806 the Patient's 6 support request into a dispenser operation 808 issue,
dosing issue 820, or
medical question 834/issue. If multiple issues present themselves, the
representative follows a
sequence that goes from the dispenser 808 to dosing 820 to medical issues 834.
The following
are exemplary issue resolution sequences.
[000290] To resolve a dispenser operation 808 issue, the representative
defines the issue,
selects the issue on her/his support screen and begins asking a number of
typical questions 810 to
narrow down the scope of the inquiry. Once sufficiently narrowed, he/she
reviews the Error
Code History 504, the Unsuccessful Dispensing Attempts History 502, and then
proceeds to the
Troubleshooting Interface 812. The Troubleshooting Interface 812 allows the
representative to
pick different troubleshooting screens 814 to work with the patient to
troubleshoot the
information. Each screen is linked to the Reference and User Manuals 230, 232.
Once the issue
is resolved, the representative prepares a documentation email 816 to be sent
to the Patient 6
defining the issue and what was done to resolve it. The email may contain
attachments from the
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references/user manuals 230, 232. The representative updates her/his notes in
the Patient Record
818.
[000291] To resolve a dosing issue 820, the representative first reviews
the Patient's 6 Opioid
Specific App's drug dispensing history 822 versus certain patient values 824.
She/he then
proceeds to select the appropriate counseling screens 826 which are designed
to assist in and
give guidance to the representative regarding how to proceed. They provide the
decision tree
relating to any decisions of whether to: (i) leave the Drug Dispenser 16
locked 828, (ii) lock the
Drug Dispenser 16 until the Patient 6 consults with their Prescriber 2 and/or
physician 828, or
(iii) unlock the Drug Dispenser 16 and allow it to dispense the dose 828.
Thereafter, the
representative will document what was discussed and how the issue was resolved
in an email 830
that is sent to the Patient 6. Then the Patient Record 818 is updated, if
required, to advise the
prescriber 832 on what transpired, and, again, if required, update the
Patient's 6 Electronic
Medical Record 24 resident on the Data Servers 10.
[000292] To resolve a medical question 834, the representative goes to his
Typical Medical
Questions 836 screen for the specific opioid and/or type of pain. The
representative selects the
appropriate subject from the screen and reviews the appropriate counseling or
triage script 838 to
ascertain whether she/he should counsel the Patient 6 or port the Patient to a
call center
physician. If the representative can counsel the Patient 6, Yes 840, the
representative discusses
the issue with the patient and makes certain recommendations (counsels the
patient) 842.
Thereafter, the representative updates the patient record 818, if appropriate,
advises the
prescriber 832, and again, if appropriate, updates the Electronic Medical
Record 24 resident on
the Data Servers 10.
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[000293] If the representative is instructed by the call center screen to
triage the patient, No
844, then the representative ports the Patient 6 to the appropriate call
center physician (or
appropriate allied healthcare professional) 846. The physician counsels the
Patient 6 or refers
the Patient 6 back to their caregiver 848. Thereafter, the physician updates
the patient record
818, advises the Prescriber 2 and/or any other designated caregivers 832, and
updates the
Patient's 6 Electronic Medical Record 24 resident on the Data Servers 10.
[000294] FIG. 18 is an exemplary embodiment of a flow chart of an Opioid
Specific App 12,
standard prescription Biometric Authentication 850 log in, aggregation of
digitally captured
information 852, 854, 856, 857, 858, 859, 860, Patient Self-Assessment 862,
Patient Self-Test
864, Patient Self-Report 866 input screens, and Drug Specific Dispensing
Algorithm 13
controlled drug dispensing Patient 6 screens 868, 870, 872, and 874. The
exemplary
embodiment is an illustration of the Patient 6 interaction to dispense an
opioid (such as
oxycodone, oxycodone/APAP, OxyContin , hydrocodone, hydrocodone/APAP,
hydromorphone,
oxymorphone, morphine, buprenorphine, etc. in their respective formulations,
e.g., abuse
deterrent, immediate release, sustained release, extended release, combination
product, prodrug,
etc.) medication.
[000295] The process begins by the Drug Dispensing App 12 alerting the
Patient 6 that it is
time to take his/her medication. If the Drug Dispensing App 12 is resident on
a smartphone, the
Drug Dispenser App 12 graphic' automatically changes to the Biometric
Authentication screen
850 when the Patient 6 unlocks the phone. Alternatively, the Patient 6 can tap
on the Opioid
Specific App 12 at any time. A tap on the Opioid Specific App 12 screen brings
up the
Biometric Authentication 850 screen. When the Patient 6 is authenticated, (i)
the Opioid
Specific App 12 effectuates a handshake with the Drug Dispenser 16 and any
digital devices for
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which an application programming interface (API) has been written, (ii) checks
to ensure the
drug has not expired 458 or exceeded its beyond-use date/prescription
expiration date 103, (iii)
confirms that it has been stored within temperature 104, 460 and humidity 106,
462 storage
parameters, (iv) checks the prescription to ensure the drug can be dispensed
within prescribing
guidelines 70, 72, 74, 80, 82, 84, 86, and then (v) moves to the Patient Self-
Assessment screen(s)
862. A click on a response value on the Patient 6 Self-Assessment Screen 862
automatically
moves to the next self-assessment screen, if required, or to the Patient 6
Self-Test screen(s) 864.
Completion of the Patient 6 Self-Test(s) automatically moves the process to
the Patient 6 Self-
Reporting 866 screen(s). Upon completion of the Self-Reporting information,
the Drug Specific
Dispensing Algorithm 13 processes the various inputs.
[000296] If nothing is found to block dispensing by the Drug Specific
Dispensing Algorithm
13, then the Patient 6 sees the Dispense screen 868. By clicking, for example,
on the Drug
Dispenser 16 dispensing button, the patient is able to dispense a dose with a
single click ¨ after
which the Drug Dispenser 16 goes back to the locked position unless the
prescription allows the
patient to dispense a number of doses on a PRN basis without waiting between
doses. It the
prescription is PRN, the Drug Dispenser 16 will be locked after the designed
number of doses
are dispensed within a specified period of time. If the Patient 6 wants to
change a prior entry
before dispensing, he/she can use the devices scroll back capabilities to
return to the right screen
and change the selection. If the Drug Specific Dispensing Algorithm 13 finds
any reason not to
allow dispensing, it selects from the appropriate drug specific screen to show
why dispensing
was rejected and to facilitate the Patient's 6 ability to avail
himself/herself of the proper
medication support 870, 872, 874.
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[000297] The exemplary embodiment of the Patient Self-Assessment screen
862, the Patient
Self-Testing screen 864, and the Patient Self-Reporting Screen 866 encompass,
for example, a
self-assessment pain measurement scale adapted from Wong Baker Faces 862; a
self-testing
motor skills test 864; and a self -reporting stool consistency observation
utilizing the Bristol
Stool Scale, a well-accepted stool measure 866. These are examples of screens
that can be
utilized in the embodiment as an input to the Drug Specific Dispensing
Algorithm 13 to decide
whether to dispense. The scales can be created, adapted, or integrated to
capture the desired
patient reported information. These can be used, for example, in addition for
use by the Drug
Specific Dispensing Algorithm 13, to titrate the opioid, monitor increasing
tolerance, gauge
medication efficacy, for better patient management, to better manage drug-
mediated side effects,
for preventative health (e.g., avoid or proactively manage a medication
mediated side-effect), for
clinical trials, and/or for post marketing surveillance, etc.
[000298] The embodiment is applicable for, as an example, clinical trials,
post-launch
surveillance, for the FDA's Risk Evaluation and Mitigation Strategy (REMS)
programs, and to
control and ensure drugs are efficacious and safe as dispensed within the Drug
Specific
Dispensing Algorithm 13 as part of a prescribed drug regimen, etc. The Opioid
Specific App 12
can be configured to capture all the patient self-assessment, self-test,
and/or self-report
information which is required by the FDA, EMA or other like governmental
agencies for
approval or regulatory compliance of opioids. The only difference from the
standard Drug
Specific Algorithm 13 are the additional input screens required. The same Drug
Specific
Dispensing Algorithm 13, decision tree, would be used for normal and clinical
trial prescribing.
[000299] FIG. 19 is an exemplary embodiment of the Digitally Captured
information 859,
858, 880, 882, 884, 886 and is illustrative of the types of digital
information, in addition to that
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captured on an Interface Device 14, such as a smartphone (e.g., diaries,
medication lists, stress
monitoring, heart rate, Sp02, diet, exercise, blood pressure, EKG, holter
values, environment
temperature, altitude, etc.) which can be collected and integrated into the
Decision Tree logic
(illustrated in FIG. 12 through FIG. 16), in the respective Drug Specific
Dispensing Algorithms
13. The availability of disease specific Apps and related disease or condition
specific digitalized
health information is rapidly emerging, making the examples in FIG. 19 wanting
not only for the
disease information but for physiologic, psychologic, lifestyle, diagnostic,
medications being
taken, digital medication ingestion, diagnostic and tracking devices, and
environmental input,
etc.
[000300] FIG. 20 is an exemplary embodiment illustration of the Drug
Dispenser 16. There
are many different permutations, from a fully disposable tamper resistant
Disposable Drug
Dispenser 16 controlled by an Opioid Specific App 12, to a Reusable Drug
Dispenser 16
controlled by an Opioid Specific App 12, to a Standalone Drug Dispenser 16
with the Opioid
Specific App 12 incorporated in the Standalone Drug Dispenser 16, etc.
Furthermore, each Drug
Dispenser 16 can be configured from one to multiple drugs. The following and
Figures 20, 21,
22, 23, 24, 25, 28, 29, and 30 are examples of the design alternatives
available and the
capabilities integrated into the novel system. The illustrations present a
reusable Drug Dispenser
16 controlled by an Opioid Specific App 12 as it represents the most complex
Drug Dispenser 16
iteration versus the Disposable Drug Dispenser 16 which presents the least
complex Drug
Dispenser 16 design.
[000301] The Reusable Drug Dispenser 890, 892, 894, 896, 898, 16 is
designed to be: (i)
controlled by an Opioid Specific App 12 resident on an Interface Device 14,
(ii) water proof, (iii)
tamper resistant, (iv) able to withstand being dropped and/or banged, to be
rugged, (v) able to
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operate and withstand hot and cold temperatures within defined temperature
ranges, (vi)
reusable, (vii) rechargeable and/or to have its battery changed, and (viii)
small enough to be
carried in a pants pocket or purse. The Reusable Drug Dispenser 16
automatically recognizes the
drug based upon the Drug Specific Drug Cassette 18, 900 docked into the
Reusable Drug
Dispenser (16). In the most secure configuration, which is designed to
restrict drug access, other
than authorized dispensed doses, to medical professionals, the Drug Cassette
18, 900 can only be
docked or removed by a healthcare professional. The Reusable Drug Dispenser 16
remains
locked from dispensing unless it receives an encrypted signal from the
authorized Opioid
Specific App 12. The Drug Dispenser 16 dispenses the opioid dose with one
click.
[000302] The Reusable Drug Dispenser 16 when interfaced through a digital
handshake with
the Opioid Specific App 12 transmits for example: (i) its (the Drug
Dispenser's) serial number,
(ii) the drug information on the Drug Cassette 16, 900, (iii) current and time
tracked historic
temperatures since the last dispense, (iv) time tracked humidity exposure
since the last dispense,
(iv) the date and time the drug was last dispensed, and any date stamped
unauthorized attempts
to open or tamper with the Drug Dispenser 16.
[000303] FIG. 21 is an exemplary embodiment illustration showing the size
of an exemplary
design for the smallest Drug Dispenser 904 and the ability to increase the
height 896 or the width
894, 910 of the Drug Dispenser 16 to accommodate more pills and/or bigger
pills and/or a
second or more Drug Cassettes 18. The width can also be expanded to
accommodate the
dispensing of two or more different medications, each which is resident on its
own Drug Cassette
18. Multidrug regimens can also be accommodated by individual cassettes as
long as each drug
is filled in a separate drug well to preclude cross contamination.
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[000304] FIG. 22 presents design renderings for different drug dispenser
configurations and
designs with different features and benefits, each being designed to meet
specific Patient 6 and
drug specific requirements. Each is simple to operate with a shared biometric
login and
dispensing button and some with an interface screen.
[000305] For example, the Dispensing Control 920 configuration is a
standalone drug
dispenser lacking external communication capabilities simply designed to
control: (i) access via
a biometric logon, (ii) dispensing per the prescribed schedule, and (iii) Drug
Cassette 18 loading,
if desirable, only by a healthcare professional. It also may contain, by
reference, some or all the
capabilities presented in the various embodiments.
[000306] The Prescription Compliance 930 standalone drug dispenser has all
the features of
the Dispensing Control 920 drug dispenser plus Wi-fl, Internet, and/or
Bluetooth
communications capabilities to enable emailing of select alert communications
to the Patient 6,
defined caregivers and/or family members. The unit has a large interactive
screen to enable the
use of an Opioid Specific App 12 to control data aggregation, input, email
communications, drug
dispensing, etc. A slightly thicker version of the standalone device could add
certain phone
capabilities which would provide this version with all the capabilities of the
Patient Management
940 system but in a standalone dispenser configuration. It may contain some or
all of the
capabilities presented in the various embodiments.
[000307] The Patient Management 940 configuration is comprised of a Drug
Dispenser 16
controlled by an Opioid Specific App 12 which is resident on an Interface
Device 14. It has all
the capabilities of the standalone dispensers 920, 930 and by reference may
incorporate some or
all the capabilities presented in the various embodiments.
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[000308] FIG. 23 is an exemplary embodiment illustration of different Drug
Cassettes 960,
18a, 18b using, as an example, OxyContin in its various dosage strengths and
pill sizes 960.
OxyContin requires different Drug Cassette sizes and configurations, and
depending on the
number of pills required for the prescription, may require the larger of the
two presented Drug
Dispensers 904, 896. Each Drug Cassette 18, 18a, 18b, 900 is designed: (i) to
use approved drug
packaging materials, (ii) to dock into the Drug Dispenser 18, 920, 930, 940,
and (iii) as a blank
cartridge which can accommodate a number of different pills, caplets,
capsules, etc. within a
specified size range. The blank Drug Cassette 900, 18, 18a, 18b is designed to
be proprietary to
the Drug Dispensers 16, 920, 930, 940. Each is marked, as part of the
automated cassette fill
operation, to allow the Drug Dispenser 16, 920, 930, 940 to recognize the drug
contained in the
Drug Cassette 18, 18a, 18b, 900 (for an individual drug in a cassette or for
each of the multiple
drugs in a single Drug Cassette 18, 18a, 18b, 900; or multiple Drug Cassettes
18 in each
respective multi-drug Drug Dispenser 1002, 1004, 1006, 1008). Each is linked
to the: (i) name
of the drug (brand and/or generic) 400, (ii) drug's NDC number 402, (iii)
drug's batch number
456, (iv) drug's expiration 458/beyond-use date, etc. The Drug Cassette's 18
label is designed to
meet all drug label regulatory requirements.
[000309] FIG. 24 presents exemplary embodiment of the Patient 6 specific
charts 970, 972,
which illustrate the relationship between when the Patient 6 took their
medication versus his/her
self-assessment, self-test, self-reported, or digitally captured symptoms
and/or diagnostic values.
This clearly shows the relationship between the medication and pain management
970 and the
medication and symptoms/side effect management 972. The charts or tables,
which can be
requested and viewed by the Patient 6 on the Interface Device 14 or the
Standalone Drug
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Dispenser 16 are designed to educate the patient 6 and promote Patient 6
prescription compliance
and persistence.
[000310] Prescribers 2 can utilize the information to ensure the medication
is efficacious for
the individual Patient 6, to titrate dosing, personalize pain therapy, and to
manage opioid
tolerance (for personalized medicine).
[000311] The respective charts, graphs, reports, etc. may be generated by
the Opioid Specific
App 12 and/or by the Integrated Support Center's 22 centralized analytics
platform 10 resident
on the Data Servers 10.
[000312] FIG. 25 is an exemplary embodiment illustration of Drug Dispensers
designed to
serve the needs of most Patients 6. Approximately half of all Patients 6 take
two medications
and 20 percent take five or more. The Consolidated Therapy App 1000
automatically senses
other Drug Specific Apps, for example 980, 982, 984, 986, 988, that are on the
Interface Device
14. It consolidates from two to many Opioid Specific Apps 12 into a single
user interface for all
drugs ¨ eliminating duplicate logins, entries, and record keeping. It in turn
digitally handshakes
with the Multi-Drug Dispenser 1002, 1004, 1006, 1008 and uses the individual
Drug Specific
Dispensing Algorithms 13 to control dispensing of each individual medication.
Furthermore, it
coordinates the dispensing schedules to have as few dispensing times, within
the respective
prescriptions, as possible. The Multi-Drug Dispensers 1002, 1004, 1006, 1008
eliminate
concerns about which drugs must be taken when.
[000313] Illustrations 1002, 1004, 1006, 1008 are exemplary of dispensing
units containing
from two drugs to five drugs. These units are standalone or can be docked into
a Multi-
Dispenser desktop unit dispenser.
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[000314] FIG. 26 is an exemplary embodiment of the integrated IT System
1010 that ties
together the Drug Dispenser 16, the Opioid Specific App 12, and the Interface
Device 14 with
the: (i) Data Servers 10, (ii) databases, and (iii) Analytics systems 10 to
ensure the Patient 6 is
receiving the best care, tailored to the Patient 6 ("personalized medicine"),
for the prescribed
Drug.
[000315] All the data collected by the Opioid Specific App 12, from the
Drug Dispenser 16,
920, 930, 940, Digitally Captured Information 852, 1012, 856, 857, 858, 859,
860, 880, 882, 884,
886, the Patient Self-Assessment screens 862, the Patient Self-Test screens
864, and the Self-
Reporting screens 868 contained within the Opioid Specific App 12, and the
respective output of
the Drug Specific Dispensing Algorithm 13 are transmitted by the Opioid
Specific App 12
through the Interface Device 14 (or the standalone drug dispenser's Internet
connection) to the
appropriate Patient 6 databases resident on the Data Servers 10. The data is
utilized to update the
respective patient screens used by the Integrated Support Center 22. The data
is also made
available to the respective Drug Registries 1016 and the related Electronic
Medical Record 24.
Any information that requires a communication with the Patient 6 and/or the
Prescriber 2 is
handled either automatically by the patient management software or by the
Integrated Support
Center 22.
[000316] The Patient's 6 information is continually analyzed by the
analytical routines both
individually for the Patient 6 as well as in comparison with treatment data
from other like
patients to ascertain if any changes in therapy may be warranted. This
analytical capability is
utilized by the Integrated Support Center 22 to assist Prescribers 2 when they
are trying to
develop a treatment plan for difficult patients. The Analytics 10 performed
may include the
Patient's 6 data, pooled patient information, as well as information from
Electronic Medical
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Records 24 (resident on the Data Servers 10 or which reside in external
databases), clinical
studies, and publications, etc.
[000317] As further example of the embodiment, the Data Servers and
Analytics 10 provide
the following, as well as other, exemplary backbone support:
[000318] For the Opioid Specific App 12: (i) assigns the App to a specific
Patient 6, (ii) links
the Drug Dispenser 16 to the Opioid Specific App 12 which in turn limits the
dispenser and App
only to work with one another, (iii) stores the Opioid Specific App 12 codes
on server, (iv)
issues, stores and links the Patient Identifier Number 160, and (v) enables
and updates the Opioid
Specific App 12 software via communication with the Interface Device 14, etc.
[000319] For the Drug Dispenser 16: (i) issues, stores and links the
Dispenser Identification
No. 158, (ii) stores all reported data in the designated databases on the Data
Servers 10, and
syncs the patient data on all the respective Interface Devices 14 (smartphone,
computer tablet,
computer, standalone drug dispenser 16, 920, 930, 940 etc.); (iii) stores
dispensing, dispensing
attempts, lock, and malfunction data reported by the Drug Dispenser 16 via the
Opioid Specific
App 12 and the Interface Device 14; (iv) transmits reports to the Patient 6
via the Opioid Specific
App 12 on request; (v) enables lock or unlock transmission from the Integrated
Support Center
22; changes the Prescription 4 on the Opioid Specific App 12 as inputted by
the Integrated
Support Center 22 representative per the Prescriber's 2 and/or authorized
healthcare
professional's instructions, and (vi) stores the authorized medical
professional identification code
required for the professional to open the Drug Dispenser 16 in order to change
or load the Drug
Cassette 18 into a Reusable Drug Dispenser 16, etc.
[000320] For the Integrated Support Center 22: (i) aggregates patient 6
data, (ii) presents and
updates data on Patient 6 specific Integrated Support Center 22 screens, (iii)
provides the ability
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to change a Patient's 6 prescription, (iv) enables the remote locking and
unlocking of individual
Drug Dispensers 16 via their Opioid Specific App 12, (v) enables drug specific
transmissions to
all Patients 6, (vi) enables simultaneously locking of all Drug Dispensers 16
for a specific Drug
in the event of a Drug recall, and (vii) enables medical professionals to
open, load, and close the
Reusable Drug Dispenser 16, (if so indicated, precludes the Patient 6, from
opening the tamper
resistant Reusable Drug Dispenser 16.) etc.
[000321] For the Patient 6: (i) prepares patient specific communications,
(ii) creates
personalized charts and reports, (iii) generates "Payer Outcomes Reports", and
required REMs
reports, etc.
[000322] For Registries 1016: (i) maintains the Registry 1016, Electronic
Medical Record 24
and Opioid Specific App 12 databases and analytics. (ii) prepares Therapy
efficacy reports, (iii)
prepares best practices reports, and (iv) through the Integrated Support
Center 22, provides
Patient 6 specific diagnosis and therapy assistance to Prescribers 2 via the
Integrated Support
Center 22 representative or via HIPPA compliant access to certain Data Servers
10 queriable
databases as requested.
[000323] For the Prescriber 2: (i) prepares and sends Patient 6 alerts,
(ii) conducts meta-data
analysis, prepares Patient 6 specific reports and shares the results with the
Prescriber 2, (iii)
provides the Prescriber 2, through the Integrated Support Center 22,
assistance/guidance based
upon Prescriber 2 requested database and analytics queries, and (iv) prepares
best practices
reports based upon patient 6 and Electronic Medical Records 24 meta-data
analysis, etc.
[000324] For Electronic Medical Records 24: (i) interfaces with the
Electronic Medical
Record 24, (ii) updates Patient 6 dispensing, compliance, and persistence
information, (iii)
updates digitally captured and patient inputted physiological, psychological,
lifestyle,
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concomitant medications, and environmental data collected by the Drug Specific
App 12 that is
required by the Drug Specific Dispensing Algorithm 13, requested be tracked by
the Presciber 2,
and/or that is required for clinical trial data submissions, (iii) updates any
Integrated Support
Center 22 counseling notes, and (iv) extracts patient 6 data, within HIPAA
guidelines, for meta-
data analysis, etc.
[000325] FIG. 27 is an exemplary embodiment illustration of how the
Integrated Support
Center 22 interfaces with the Opioid Specific App 12, the Patient 6, the
Prescriber 2, and the
Electronic Medical Record 24.
[000326] The Integrated Support Center's 22 interactions with the Patient 6
can be instigated
by a number of different scenarios and take on many different forms. Examples
include but are
not limited to: (i) receipt of a Patient 6 alert from the Patient's Opioid
Specific App 12; (ii)
Patient 6 calls; (iii) answering Patient 6 questions about the Drug Dispenser
16, Opioid Specific
App 12, the drug, or their pain therapy; (iv) Patient 6 counseling within the
support center's
guidelines; (v) locking the individual patient's Drug Dispenser 16 based upon:
(a) an Opioid
Specific App 12 alert, (b) an Integrated Support Center 22 Analytics alert,
(c) a patient 6
conversation, etc.; (vi) unlocking the individual patient's 6 Drug Dispenser
16 based upon: (a) a
conversation with the Patient 6, (b) a conversation with the Prescriber 2,
etc.
[000327] In addition, as an example, the Integrated Support Center 22
provides: (i)
"Compliance" and "Adherence" support; (ii) outbound patient 6 telephone calls;
(iii) patient 6
monitoring; (iv) emails and/or calls the patient's 6 Prescriber 2 and/or
physician to recommend a
therapy change, etc.; (v) patient 6 disease management education; (vi) ensures
patient 6 has
access to their drug; (vii) as required, works with payers to obtain coverage
for high cost
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medications; (viii) looks for prescription financial assistance programs; (ix)
patient 6 education
and reeducation; (x) patient 6 follow-up, and (xi) Medical Affairs support.
[000328] The Integrated Support Center's 22 interactions with the
Prescriber 2 can be
instigated by a number of different scenarios and take on many different
forms. Examples
include but are not limited to: (i) locking or unlocking a specific patient's
Drug Dispenser 16; (ii)
changing the prescription 4; (iii) patient 6 specific physician support using
the Integrated Support
Center's 22 Data Server's and Analytics 10 to ascertain patient specific
treatment alternatives;
(iv) assist with patient 6 specific data analysis; (v) provide
disease/condition specific
information; and (vi) Medical Affairs support, etc.
[000329] FIG. 28 is an exemplary embodiment illustration of the assembly
and locking
mechanism for the Disposable Drug Dispenser's 16 clamshell design. The
interior of the top of
the clamshell 1020 incorporates hinges that marry with the hinges on the
inside of the bottom
clamshell interior 1034. These are locked together with a hinge pin 1022 that
is threaded
through the holes in the respective hinges, much the same as the hinges are
held together on most
common entry door hinges.
[000330] The top 1020 and bottom 1034 clamshells are locked closed together
by use of a
micro actuator moved locking bar 1028. When the top of the clamshell is closed
with the bottom
clamshell, the locking bar is pulled down by the micro actuator and the hook's
male members
dock into the respective female orifices on the locking buttons 1030.
[000331] The design incorporates integrated supports to ensure the
integrity and durability of
the design. They are also instrumental in adding strength, as required, for
adding anchors for the
respective Disposable Drug Dispenser's 16 internal components.
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[000332] The design eliminates the ability to open the Disposable Drug
Dispenser 16 without
an authorized signal to cause the micro actuator to unlock 1028. The Top Cap
1026 is fitted to
close the top of the Bottom Clamshell 1034. The top of the Top Cap 1026 covers
the top of the
Hinge Pin 1022 and holds it in place. The Bottom Cap 1036 covers and provides
a holding point
for the bottom of the Hinge Pin 1022 and holds it in place.
[000333] The right interior to the Top Cap 1026 provides for a dock for the
end of the Lock
Bar 1028 and allows it to be supported when it moves up and down to lock or
unlock, as
required. The Bottom Cap 1036 provides the seat that supports the
Microacturator 1028 that
locks and unlocks the clamshell by moving the Lock Bar 1028 up and down.
[000334] The Top 1026 and Bottom 1036 Caps are secured to the Bottom
Clamshell Interior
1034 by screws and/or glue that securely marry each of the pieces together
from the interior
(there are no exterior screws). The unit then forms a ridged bottom clamshell
platform 1034 for
the Top Clamshell Interior 1020 to dock with. When the Drug Dispenser 16 is
closed, it forms a
sturdy, tamper resistant housing for the Drug Cassette 18, 18a, 18b, 900.
[000335] In one design embodiment, in order to provide the requisite
downward pressure to
ensure the unit is both water and dust resistant and to contribute to its
rugged design, the Drug
Dispenser 16 has a Clasp Lock 1032 designed to exert the desired level of
pressure on the
respective closing clamshell 1020, 1034 joints to secure design integrity.
[000336] In this example, the Top Cap 1024 incorporates a one click
dispensing button. The
Bottom Cap 1038 houses the dispensing port. In the examples presented in FIG.
22, the top and
bottom caps are solid enclosures. Dispensing is accomplished by a single click
on the
combination biometric logon, screen on, and dispensing button on the lower
front center of each
of the Drug Dispensers 16. Dispensing is accomplished by a drawer that opens
out to the left at
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the bottom of the Drug Dispenser 922, 932, 942 when dispensing is authorized
and the dispense
button clicked. Dispensing in alternative designs can also be accomplished by
dispensing from
the bottom of the Drug Dispenser 16 when the one click dispensing button is
depressed.
[000337] Another example includes the Disposable Drug Dispenser 16. The
external case on
the Disposable Drug Dispenser 16 is a sealed unit where there is no entry
after the Drug Cassette
18 with the specified opioid is docked into the Disposable Drug Dispenser 16
and the external
case component parts are glued or laser bonded to form a unified case. Drug
dispensing is
controlled by the Opioid Specific App 18. Dispensing takes place by clicking
on the dispensing
button. The drug is dispensed at the bottom of the Disposable Drug Dispenser
16 or via some
kind of catchment area or dispensing drawer. The dispenser opening is covered
from inside the
Disposable Drug Dispenser 16 by an intrusion deterrent closure once the opioid
is dispensed.
This creates a disposable housing that can only be penetrated via destruction
of the dispenser
housing which triggers a tampering alert to the Integrated Call Center 22.
[000338] FIG. 29 is an exemplary embodiment of the Drug Dispenser's 16
electronics and
features schematic. The Drug Dispenser's 16 system is comprised of an
Applications Processor
1048 that contains the units Firmware, individual Drug Dispenser 16 serial
number, and manages
all functions. The main unit components are the: (i) communications
connectivity 1042 module,
(ii) its data transfer capability 1046, (iii) the units sensors and/or
applications 1044 that allow the
unit to authenticate the user, sense efforts to tamper/open the unit without
authority, measure
drug storage temperature and humidity, to time stamp an action or event (clock
function), and
locate the unit via GPS; (iv) the display module 1050; (v) the Power
Management and recharge
system 1056; (vi) Memory management 1054; (vii) Cassette Controller 1040 which
enables
dispensing as well as the ability to read specific drug cassette information;
(viii) the Dosage
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Dispenser system 1052; and (ix) the various components designed to facilitate
and protect the
different system functions 1058, etc.
[000339] FIG. 30 is an exemplary embodiment of the placement of electronics
and
mechanical components on the outside and within the Disposable Drug Dispenser
16. The front
of the Disposable Drug Dispenser 16 contains an On Off Button 1064 which the
user can depress
if the Drug Dispenser 16 does not automatically come on when the Opioid
Specific App 12
handshakes with the Drug Dispenser 16. When a handshake is effectuated or the
On Off Button
1064 is pushed, a blue LED light comes on 1066. The LED light 1066 turns to
green if the unit
is ready to dispense, yellow 1066 if it is awaiting authority to dispense, and
red 1066 if the unit is
locked and will not dispense. The display 1068 resides on the center of the
face, Front View, of
the Disposable Drug Dispenser 16.
[000340] A number of components fit on the Top Clamshell Interior 1060;
these include: (i)
the On Off Button 1064 on the front of the Disposable Drug Dispenser 16 and
the switch 1070
on the interior top clamshell 1060 (ii) the LED status light 1066 LED and
electronics 1074; (iii)
the battery, power management, Wi-Fi, Bluetooth, GPS and antenna systems 1072;
(iv) the LED
Screen 1068 and its electronics and management system 1076; and (v) the drug
dispensing
actuator arm and dispensing lock 1078. The Bottom Clamshell Interior 1062
houses the: (vi)
single click Dispensing Button 1080; (vii) the Logic, Controls, Processor and
Memory Board and
its various components 1082; (viii) Temperature and Humidity sensors 1084;
(iv) the Attempting
Tampering Sensors 1090; (x) the Cassette Dispensing Motor and Controller 1088;
(xi) the Drug
Cassette Reader 1086; (xii) the Clamshell Lock micro actuator controller 1094,
and (xiii) the
Dispensing Door Controller 1092.
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[000341] FIG. 31 is an exemplary embodiment of the correlation of opioid
plasma levels and
pupil size using oxycodone as the example. Each opioid has its own pupil size
and plasma level
relationship. Pupil size, when normalized for the individual patient, can be
an indicator of opioid
plasma level. Pinpoint pupils are a sign of opioid overdose but are not
pathognomonic (e.g.,
pontine lesions of hemorrhagic or ischemic origins may produce similar
findings). Marked
mydriasis rather than miosis may be seen due to hypoxia in opioid overdose
situations. So, pupil
size can be utilized as a screening indicator for overdose.
[000342] As an example, the relationship between the plasma level of
oxycodone and the
analgesic response will depend on the patient's age, state of health, medical
condition, extent of
previous opioid treatment, and concomitant medications which may affect pupil
dilation. The
minimum effective plasma concentration of oxycodone to achieve analgesia will
vary widely
among patients, especially among patients who have been previously treated
with potent agonist
opioids. Thus, patients need to be treated with individualized titration of
oxycodone dosage to
the desired effect. The minimum effective analgesic concentration of the
oxycodone for any
individual patient may increase with repeated dosing due to an increase in
pain and/or
development of tolerance.
[000343] A 1100 depicts the time course of pupil diameter over 24-hour
period in 4 subjects
receiving 10-, 15-, and 20-mg oral dose of oxycodone (pilot study). The inset
1102 depicts the
linearity of the area under the effect curve (AUEC) for pupil response across
the 3 doses in
individual subjects. The indication is that there is a maximum percent (%)
change from baseline
in pupil diameter within time ranges after an oxycodone dose (applies to all
opioids).
[000344] B 1104 presents the individual time course of pupil diameter in 16
subjects after 15-
mg dose of oxycodone (gray lines) in both pilot and main studies. This shows
the range
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differences between individuals. It illustrates that the pupil does not move
into "pinpoint
pupils", overdose, or mydriasis under normal dosing. The black line represents
the mean pupil
diameter over time. Thus, a personalized Patient 6 baseline can be used as a
basis for future
pupil size comparison to ascertain if the Patient 6 is: (i) overdosed, (ii)
could become overdosed
if they take another opioid dose, and (iii) within normal range and should be
allowed to take the
opioid dose.
[000345] FIG. 32 is an exemplary embodiment of a how pinpoint and dilated
pupils can be
used as diagnostic indicators. Oxycodone pharmacokinetic-pharmacodynamic model
prediction
of pupil diameter (lines) and observed data (squares) illustrated in 4
representative subjects 1106,
1008, 1110, 1112 receiving 15 mg oxycodone illustrate the diagnostic accuracy.
The four
patients illustrate the oxycodone goodness of fit with the parent drug
equilibration model to the
observed data. The high correlation was also tested on multidose data. The
results were not
significantly different from the estimates obtained with the 15-mg dose.
[000346] Using the images captured by Iris scan biometric logon or Opioid
Specific App 12
logon to measure pupil size enable setting a pupil diameter opioid plasma
level curve over time
baseline against which future pupil size measurements can be compared. Iris
scan are being
incorporated into smartphones by Samsung, Apple, Microsoft, LG, HP, Fujitsu,
Vivo, ZTE,
Alcatel, UMI, etc. Using the iris scan to measure the pupil ensures the
patient's pupil is the one
being measured and provides further security against opioid diversion.
[000347] The Patient's 6 pharmacokinetic-pharmacodynamic opioid baseline
curve can be
established by taking pupil size measurements before taking the first opioid
dose and then at
specified time intervals during the Opioid Specific App 12 set up process.
Thereafter, any
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statistically significant indicator that there is a shift from the baseline
can require a confirmatory
set of pupil measurements and/or alert the Integrated Support Center 22.
[000348] Once personalized (required by individual differences as well as
concomitant
medications), the algorithm can use pupil diameters below or above a certain
pupil diameter to
preclude dispensing the dose. The use of the predictive curve and the effects
of subsequent
doses to ascertain if the patient would remain within the safe range can be
used to allow the dose
to be dispensed. If the range falls between the safe to dispense range versus
the do not dispense
value, then a confirmatory test can be utilized to educate the dispense or do
not dispense the dose
decision, regardless if the prescription would otherwise allow the dose. (The
integrated support
center would have access to this information to help educate their decision.)
Doses below or
above a certain pupil diameter would not be dispensed.
[000349] FIG. 33 illustrates an exemplary embodiment of the present
invention that explains
what an eyelid 1120, iris 1122, pupil 1124 and sclera 1126 of the eye are. It
shows the difference
in eye dilation under bright light 1128 and dim light 1130.
[000350] FIG. 34 is an exemplary embodiment of a method to detect,
authenticate, and
capture iris and pupil data to make a dispense or do not dispense screening
decision.
[000351] The Eye Image Capture 1140 is accomplished, for example, by an IR
(infrared)
LED and a dedicated iris camera resident on the smart phone. The camera is
designed with a
special image filter which receives and recognizes the reflected picture of
the irises with a red IR
LED light.
[000352] The setup process basically involves lifting the phone to eye
level at arm's length
and waiting for the phone to capture your iris data. It's able to detect which
part of the image is
your iris, then deletes the rest of the information, like your eyelid, pupil
and sclera (white area).
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Once the iris is registered, the phone stores the iris data as an encrypted
piece of code in the
Databases 1156. Thereafter, when the user tries to access the phone, or a drug
specific app
which incorporates the dispense or do not dispense pupil algorithm, the LED
and camera work
together to capture the iris, then extract the file and compare the pattern
with the code to allow
access 1158.
[000353] Once the Image of the eye is Captured 1142, then the program
Detects the Iris and
Eyelid 1144, and then extracts the Iris Area 1146. The program then removes
any eyelid
artifacts 1148 and then normalizes the Iris 1150. Then the pupil detection
program normalizes
the Pupil Areas 1150, 1152.
[000354] Normalization uses the size of the Iris versus the baseline of the
Pupil stored in the
Databases 1156. This allows adjustment of the pupil size for the difference in
distance from the
camera to the Iris 1140. The digital brightness values enable the brightness
adjustment in order
to correlate the pupil size to the brightness and normalize the pupil size
against the baseline.
[000355] The normalized data is then translated into a format that may be
utilized by the
Authenticated 1158 patient specific program to compare the values to the
established normalized
patient specific miosis, and mydriasis data ranges to make a dispense or do
not dispense decision
1160.
[000356] FIG. 35 is an exemplary embodiment of pupil size logic utilized to
make a dispense
or do not dispense decision. The process begins with a smart phone Iris Scan
1160 used to
authenticate 1162 the right patient is accessing the system. If the patient is
not authenticated, No
1164, he/she is required to try again 1160 until he/she is authenticated, Yes
1166. The program
then accesses the normalized pupil measurement 1168 and ascertains if the
pupil is larger than,
for example, 8mm. If Yes 1172, then the decision is Do Not Dispense 1174. If
the pupil is
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smaller than 8mm, No 1176, then the algorithm ascertains if the pupil is less
than, for example
2.5 mm 1178. If it is not smaller than 2.5 mm, No 1180, then the decision is
to Dispense 1182.
However, if the pupils are less than 2.5 mm, Yes 1184, then the algorithm
checks if the pupil size
is less than 2.0mm 1186, if Yes 1188, then the decision is Do Not Dispense
1174. If the pupil is
not less than, for example, 2.0 mm, No 1190, then the algorithm checks the
patient's pupil size
versus the patient's traditional pupil sizes in order to ascertain if this is
within historic norms or
if there has been a rapid decrease in pupil size versus historic pupil size
values 1192. If Yes
1194, then the decision is Do Not Dispense 1174. If the answer is No 1196
there has not been a
rapid decrease in pupil size versus historic norms (some of the historic norms
could be derived
from iris scan data that is used by the patient to access his/her smart phone,
etc., over time), the
program confirms, for example, that the pupil size is between 2.0 mm and 2.5
mm 1198. If Yes
1200, then the program would proceed to a confirmatory test 1202 designed to
decrease the
chance of a false positive, i.e., a false decision not to dispense. In this
exemplary, we will use a
Motor Skills Self-Test. However, other values tied to a drug mediated
physiologic or
psychologic change can be utilized. Examples include things such as pupil
reaction to light/pupil
reactivity, pulse rate, blood pressure, heart rhythm, body temperature, amount
of sleep, gait,
balance, speech pattern, tone, eye movement, a specific diagnostic value, CO2
saturation,
respiratory rate, etc. Some may be digitally captured (passively monitored) by
a device like a
wearable monitor (e.g., FitBit), implanted monitor, wearable diagnostic,
consumed diagnostic,
smart watch, smart phone, etc. that would not require an elicited response
from the patient.
[000357] Another basis for making a dispense versus do not dispense
decision is the standard
deviation from the Patient's 6 pharmacokinetic-pharmacodynamic opioid baseline
curve.
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[000358] The value used to ascertain whether an Oxycodone dose should or
should not be
dispensed may be based upon a change in normalized pupil size versus an
established pupil size
that is equal to or greater than a defined amount. It may also be a
combination of a fixed
number, e.g., for mydriasis and/or pinpoint pupils as well as a delta change
from the baseline,
whichever applies. The objective is to keep the Patient 6 from taking an
opioid dose that would
result in an overdose.
[000359] FIG. 36 is an exemplary embodiment of a three screen 1210, 1212,
1214 motor
self-test. Each screen is comprised of three dots which are randomly placed on
the screen. Each
is a different randomized color. One randomized dot is solid and designated as
the dot that must
be clicked upon. The titles on each screen also change positions and colors
randomly. Based on
the program logic, a decision is made whether or not the patient's cognition,
based upon the
motor skills self-test, is sufficient to Dispense 1182 the opioid dose or to
preclude the opioid
from being dispensed, Do-Not-Dispense 1174. The logic behind the Motor Skills
Self-Test is to
measure response time and accuracy from baseline test values to ascertain if
there is a sufficient
deterioration in response time and accuracy to warrant a Do-Not Dispense 1174
decision.
[000360] FIG. 37 is an exemplary embodiment of the Motor Skill Self-Test
logic to make a
dispense or do not dispense an opioid dose decision. When the first Motor
Skill Test 1 screen
1220 is presented, it asks the Patient 6 to click on the solid dot 1222. If no
response is made, No
1224, after five seconds 1226, the screen for Motor Skill Test 1 1220 is
refreshed with new
button colors and locations and the test start time is reset to zero. If at
the second attempt there is
still no response after five seconds, No. 1224, then the program sets the did
not click value to =1
1228 and sets the start time as the actual time less 3 seconds 1230 and
proceeds to the next
screen 1238. If the Patient 6 clicked on the screen or the solid circle 1222,
Yes 1232, the
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program indicates the patient clicked on the solid button = 1 1234 or did not
click on the solid
button = 0 1234. Then the program sets the start time to the actual time 1236
and then proceeds
to the next test screen 1238.
[000361] When the Motor Skill Test 2 screen 1240 is presented, it asks the
Patient 6 to click
on the solid dot 1242. If no response is made, No 1244, after five seconds
1246, the screen for
Motor Skill Test 2 1240 is refreshed with new button colors and locations and
the test start time
for Skill Test 2 is reset once to zero. If at the second attempt there is
still no response after five
seconds, No. 1244, then the program sets the did not click value to =1 1248,
and makes the Do
Not Dispense the opioid dose 1174 decision and stops the algorithm. If the
Patient 6 clicked on
the screen or the solid circle 1242, Yes 1250, the program indicates the
patient clicked on the
solid button = 1 1252 or did not click on the solid button = 0 1254. Then the
program sets the
start time to the actual time 1254 and then proceeds to the next test screen
1256.
[000362] When the Motor Skill Test 3 screen 1258 is presented, it asks the
Patient 6 to click
on the solid dot 1260. If no response is made, No 1262, after five seconds
1264, the screen for
Motor Skill Test 3 1258 is refreshed with new button colors and locations and
the test start time
for Skill Test 3 is reset once back to zero. If at the second attempt there is
still no response after
five seconds, No. 1262, then the program sets the did not click value to = 1
1266, and sets the
Skill Test 3 start time as the actual time less 5 seconds 1268. If the patient
clicked on the screen
or the solid circle 1260, Yes 1270, the program indicates the patient clicked
on the solid button =
1 1272 or did not click on the solid button = 0 1272. Then the program sets
the click time to the
actual time 1274 and then proceeds to the Dispense/Do Not Dispense logic 1276.
[000363] FIG. 38 is an exemplary embodiment of the dispense or do not
dispense an opioid
dose motor skill test logic. The logic begins with the question if the patient
accurately clicked on
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the solid dots, total = 3 1280. If the answer is No 1282, then the formula
checks to see if the
total clicked value equals 2 or 3 1284. If No 1286, then the decision is Do
Not Dispense the
opioid dose 1174.
[000364] If the Patient 6 accurately clicked on the solid dots 1280, Yes
1288, if the total time
to click on the solid dots, for example, equals or is less than 2 seconds more
than the baseline test
and/or series of test responses 1290 (e.g., time less baseline must equal less
than 2 seconds), Yes
1294, then the decision is to Dispense 1182 the opioid dose. If the answer is
No 1292, then the
decision is Do Not Dispense 1174 the opioid dose.
[000365] FIG. 39 is an exemplary embodiment of the opioid dispensing
algorithm designed
to reduce the number of false positives (e.g., decisions not to dispense). In
this case, if the pupil
scan decision is to dispense 1182, the decision is then to dispense the opioid
dose 1182.
[000366] However, if the result of the pupil scan 1160 was to proceed to a
confirmatory test
1202, in this case the Motor Skill Self-Test 1210, 1212, 1214, then the
outcome of the
confirmatory self-test will either be to Dispense 1182 or Do Not Dispense 1174
the opioid dose.
[000367] There can be more than one confirmatory test. As an example,
opioid confirmatory
tests could include one or more digitally captured diagnostics and/or
biomarkers such as pupil
reactivity, respiratory rate, oxygen saturation level, change in body
temperature, activity level,
amount of sleep/naps, heart rate, blood pressure, gait, dizziness,
constipation, changes in weight,
etc. They could also include certain physiological and/or psychological self-
assessments, self-
tests, or self-reported information/observations, etc.
[000368] FIG. 40 is an exemplary embodiment of algorithm logic designed to
reduce the
number of false positives (e.g., do not dispense). It begins by ascertaining
if the pupil diameter
is within the normal range of, for example, from 2.5 mm to 8 mm 1300. If Yes
1302, then the
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program indicates that the medication should be dispensed 1182. If the answer
is No 1304, then
the program proceeds to ascertain if the patient passed the confirmatory test,
in this case The
Motor Skills Confirmatory Test 1306. If the patient passed the confirmatory
test, Yes 1308, then
the program indicates that the opioid dose should be Dispensed 1182. If the
answer is No 1310,
then the program indicates the opioid dose should not be dispensed 1174.
[000369] FIG. 41 is an exemplary embodiment of using patient self-
assessment and self-
reporting information to make a Dispense 1182 versus a Do Not Dispense 1174
the opioid dose
decision. As an example, if the Patient 6 is taking an opioid, the patient may
want to avoid
taking more medication if the Patient 6 is or is becoming severely
constipated. In this case, for
example, a combination of a self-assessment of the patient's abdominal pain
level 1320, and self-
reported consistency of the patient's last stool 1322, and the number of bowel
movements 1324,
would allow an informed Dispense 1182 or Do Not Dispense 1174 the opioid dose
decision,
even if the Prescription 4 would otherwise allow the medication to be
dispensed before talking
with a medical professional. Under this embodiment this would be before
talking with the
Integrated Support Center 22. This routine can also be utilized to alert the
Patient 6 that he/she
may be getting constipated and that they should consider taking a laxative or
talking with their
Prescriber 2, etc.
[000370] FIG. 42 is an exemplary embodiment of the program routines that
can utilize
patient self-assessment and self-reported information to make a dispense or do
not dispense
decision. To make a dispense 1182 or do not dispense 1174 the opioid dose
decision the
program would ascertain if the pain level is greater than a predefined level,
for example level 2
1330; if No 1332, then the decision is Do Not Dispense 1174. If the pain level
is greater than 2
1330, Yes 1334, then the program proceeds to ascertain if the stool
composition of the last bowel
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movement was greater than 3 1336; if No 1338, then the decision is Do Not
Dispense 1174. If
the last stool consistency was greater than 3 1336, Yes 1340, then the program
ascertains if the
patient had one or more stool movements in the last 48 hours 1342; if No 1334,
then the decision
is Do Not Dispense 1174. If the answer is Yes 1346, then the decision would be
to Dispense
1182 the opioid dose.
IV. EXAMPLES
[000371] The embodiment of the invention can be utilized, for among other
uses, 1) to
improve the drug's safety profile by ensuring proper, personalized opioid
prescribing and
prescription management (e.g., personalized dispensing), 2) to ensure the
medication is
efficacious, 3) as a diagnostic aid/tool, 4) to titrate the medication, 5) to
preclude drug mediated
adverse events, 6) to preclude over dosing, 7) to preclude under dosing, 8) to
decrease the chance
of misuse, 9) to decrease the chance of abuse, 10) to decrease the chance of
overdosing, 11) to
increase compliance with the medication prescription, 12) to prevent the
patient from
inadvertently taking a duplicate dose, 13) to decrease the chance of
addiction, 14) to decrease the
chance of dependence, 15) to better manage opioid tolerance, 16) to manage
medication
withdrawal, 17) to enable PRN dosing, e.g., manage "Patient Controlled Oral
Analgesi aTM"
(PC OATM), 18) to preclude drug divergence, 19) to guard against accidental
ingestion of the
opioid by a child, 20) to avoid drug-drug interactions, 21) to better manage
medication mediated
side-effects, 22) to promote prescription persistence, 23) to shift any
potential liability from the
drug manufacturer or the opioid Prescriber 2 to the Patient 6, 24) to capture
patient self-
assessment, self-test, self-reported, and digitally captured information
required to control drug
dispensing and/or to meet clinical trial regulatory agency reporting
requirements, 25) to capture
opioid related side-effects to assist in better patient management, 26) to
streamline opioid Risk
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Evaluation and Mitigation Strategy (REMS) reporting, 27) to streamline
Prescription Drug
Monitoring Programs (PDMPs) record keeping and reporting, etc. In short, to
personalize opioid
therapy by improving the opioid's drug/safety profile.
[000372] Ideal opioid management would have the physician evaluate the
patient each time
prior to allowing the patient to take his prescribed opioid dose/medication.
The physician would
ascertain how well the current dose manages the patient's pain/symptoms and
would be looking
for signs of opioid side effects, addiction, dependence, misuse, abuse,
possible bad drug-drug
combinations, etc. prior to authorizing the patient to take the dose. That
way, the physician
could change/refine the dosage for the patient and/or preclude the patient
from taking the opioid
in the event the physician ascertained that the dose was not warranted and/or
that the dose could
lead to a serious opioid mediated event and/or undesirable side effect. Having
a physician
approve each dose before it is taken by the Patient 6 is neither realistic nor
cost effective, the
embodiment of the invention incorporates many of the consideration a physician
would consider
prior to allowing a patient to dispense an opioid dose from the Drug Dispenser
16.
A. Opioids
[000373] Opioids serve as an excellent exemplary of how the embodiment of
the invention
can be utilized to improve opioids and other medications management and
patient outcomes.
B. Background
[000374] The following describes some, but not all, of the key opioid side
effects as
background for the subsequent opioid examples of the embodiment:
[000375] Cognitive Impairment - It is well known that larger doses of
opioids are markedly
impairing, leading to drowsiness, lethargy, and even death. At least one
prospective study has
demonstrated that those with chronic pain on opioid therapy have cognitive
deficits including
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reduced spatial memory capacity and impaired performance in working memory
assessment
(Schiltenwolf et al., 2014).
[000376] Respiratory depression - Opioids adversely affect the respiratory
system. Carbon
dioxide (CO2) levels in the blood stimulate our respiratory drive. As
breathing slows down, CO2
levels increase, which stimulates the brainstem to increase the respiratory
rate.
[000377] Low oxygen levels do not stimulate breathing so sensitivity to CO2
levels is an
important function of nerve cells in the brainstem. Opioids block that
feedback loop. When an
individual overdoses on an opioid, the high levels of opioid will decrease
alertness and induce
sleep. During sleep, it is the CO2 feedback loop that keeps people breathing.
However, when
blocked by the high levels of an opioid, breathing slows or stops and the
person who has
overdosed literally suffocates.
[000378] Heart Rate - Heart rate may become either rapid or very slow. Some
opioid users
may also develop postural hypotension or a severe fall in blood pressure on
standing up from a
sitting or lying position.
[000379] This is also problematic for individuals with lung disease or
sleep apnea. People
with chronic lung disease often need elevated carbon dioxide levels to
stimulate them to breathe
more deeply. Taking opioids will blunt this response, causing people with lung
disease to
breathe slower and therefore have low oxygen levels.
[000380] Sleep apnea is similar as people periodically stop breathing at
night until their
carbon dioxide levels get high enough to stimulate their brain to signal them
to gasp for breath.
When opioids interfere with this response the effect can be life threatening.
Opioids have been
shown to worsen the apnea episodes in those with sleep apnea (Jungquist,
Flannery, Perlis, &
Grace, 2012).
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[000381] Miosis ¨ Opioid use results in the formation of small, constricted
pupils, similar to
how pupils respond to bright light.
[000382] Constipation - Opioids cause sluggish peristaltic movements in the
digestive tract.
This causes stasis or loss of movement of the intestinal contents and leads to
severe constipation,
especially in the case of long-term use.
[000383] Drowsiness or Sedation - Opioids, and in particular morphine, are
known to cause
severe sedation and drowsiness.
[000384] Myoclonus ¨ High doses of opioids can result in muscle rigidity
and abnormal
movement of the limbs and muscles.
[000385] Hyperalgesia - Opioid-induced hyperalgesia (01H) is another side
effect of the use
of opioids. Opioid hyperalgesia is a phenomenon where the body develops an
increased
sensitivity to pain secondary to opioid use (hyper ¨ over or excess, algesia ¨
sensitivity to pain).
[000386] Pain is an important part of our body's defense system, warning us
of current or
impending damage or injury. As opioids decrease our brain's sensitivity to
pain signals coming
from the rest of the body, our brain begins to compensate by increasing our
recognition of and
sensitivity to pain. The pain neurons going to the brain actually change to
make them more
responsive to pain and increase our perception of pain. This change is called
neuroplasticity of
the nerve cell. Many mechanisms are believed to be involved in these changes
(M. Lee,
Silverman, Hansen, Patel, & Manchikanti, 2011). The result of this change is
that after opioid
levels decrease, our pain fibers are more sensitive than before consuming the
opioid which
results in an increase in pain.
[000387] Unfortunately, increasing pain can also mean disease progression
or the
development of tolerance to the current opioid dose. For these conditions,
opioid doses are
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usually increased. In contrast, the treatment of opioid hyperalgesia is the
decrease or
discontinuation of opioids.
[000388] Tolerance and withdrawal - Tolerance occurs when the body has
developed
physiologic (both neuroplastic and chemical) changes that result in decreased
effectiveness of the
medicine necessitating a higher dose to get the same effect. Withdrawal is the
unpleasant
symptoms that develop upon decrease or discontinuation of that medicine. Brain
changes and
measurable withdrawal symptoms can occur after one dose of opioid (Rothwell,
Thomas, &
Gewirtz, 2012).
[000389] In clinical practice, withdrawal symptoms can occur after five to
seven days of
opioid medication (Anand et al., 2010). Withdrawal symptoms may consist of
myalgia (muscle
pain), chills, sweats, anxiety, increased pain, rapid heartbeat, dilated
pupils, yawning, diarrhea
and nausea.
[000390] Withdrawal is extremely unpleasant and can be relieved by taking
another opioid
dose. Tolerance and withdrawal are not considered addiction. Tolerance occurs
because of the
physiologic changes resulting from exposure to opioids. Withdrawal is the
unpleasant physical
and emotional symptoms that occur upon withdrawal of the opioid after
tolerance has developed.
[000391] Addiction - Addiction is characterized by inability to
consistently abstain,
impairment in behavioral control, craving, diminished recognition of
significant problems with
one's behaviors and interpersonal relationships, and a dysfunctional emotional
response.
[000392] Death - There is one factor that is often not considered when
prescribing opioid
pain medications ¨ the overall increase in deaths. Opioids account for more
deaths than any other
medication. The medical ethical principle of non-maleficence (do not harm) now
extends
beyond the exam room: the interaction between a physician and his/her patient
may adversely
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affect the life and health of someone else who is not a part of the medical
decision. Impairment
from opioids may lead to unintentional death by motor vehicle crashes or
workplace safety
incidents. Opioid use may also lead to falls and increase mortality rates in
the elderly.
[000393] Benzodiazepines - It is also important to realize that the risk of
death is markedly
increased when opioids are taken with benzodiazepine medications. The
combination of opioids
and benzodiazepines are the leading cause of overdose deaths when multiple
medications are
involved (Calcaterra, Glanz, & Binswanger, 2013). Despite this danger,
benzodiazepines are
prescribed to about 30% of people on chronic opioid therapy (Nowak, Abou-
Nader, & Stettin,
2014).
C. Opioids Prescribing
[000394] Prescribing
[000395] The Opioid Specific App 12 is designed to be customizable for each
Patient 6.
When the Prescriber 2 enters the prescription 4, he/she may select from a list
which includes all
the potential opioid side effects and/or any information that is required by a
regulatory agency,
such as the FDA or EMA, for a clinical trial and/or for drug approval. The
Prescriber 2 can also
choose how often the patient will be prompted for each piece of information,
e.g. every time
before dispensing the opioid, at specified intervals, when another value
occurs, when another
value occurs over or under a specified value or within a specified range, etc.
These values may
include digitally captured or patient entered physiologic, psychologic,
lifestyle, concomitant
medications taken since the last opioid dose, and/or environmental
information. The captured
information may or may not be utilized by the Opioid Specific Dispensing
Algorithm 13 to make
a dispense or do not dispense the dose decision.
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[000396] The values are stored by the Opioid Specific App 12 on its related
Interface
Database 278 files resident on the Interface Device 14, or on the Standalone
Drug Dispenser 16,
and synchronized with the Patient Database 152 stored on the Data Servers 10
for future
reference. The information is organized for utilization by the Patient 6, the
Drug Specific
Dispensing Algorithm 13, care givers, the Patient's 6 physician and/or
Prescriber 2 to better
manage opioid dosing and/or the Patient's treatment/therapy, and for trending
and analysis by the
Opioid Specific App 12 and/or the analytics programs on the Data Servers 10 to
assist in the
development of optimal therapies.
[000397] Creating The Personalized Drug Dispensing App
[000398] Once the prescription is electronically entered, submitted 150,
the App Generation
Program 200 on the Data Servers 10 creates a personalized Patient 6 Opioid
Specific App 12 and
creates and links together the related Patient 6 records/databases resident on
the Data Servers 10.
Thereafter, it sends a download link to the Patient 6, with copies to
appropriate personnel, e.g.,
the caregiver, Prescriber 2 and the Pharmacy 8, etc., for the Patient 6 to
download the Opioid
Specific App 12 onto the Interface Device 14 or Devices 14 or onto a
standalone Disposable
Drug Dispenser 16. If the Patient 6 has any problem downloading the Opioid
Specific App 12,
the caregiver, the Prescriber 2 or her/his staff, the Integrated Support
Center 22 and/or the
Pharmacy 8 staff can assist the Patient 6 in resolving the problem.
[000399] Personalizing The Patient Specific Opioid Specific App
[000400] Upon downloading the personalized Opioid Specific App 12, the
Patient 6 opens
the Opioid Specific App 12 and inputs the requisite Patient 6 information
which enables the
biometric login 280, links the Patient 6 to the Prescription 4 and to the
Opioid Specific App 12.
[000401] Loading The Drug Cassette into The Reusable Drug Dispenser
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[000402] In the Reusable Drug Dispensers 16, opening the Drug Dispenser 16
requires a
unique Dispenser Identification No. 158 which is automatically issued by the
Patient Database
152 App Generation Program 200 when an e-Prescription 4 is Submitted 150. An
Authorization
Code is required to open the Reusable Drug Dispenser 16 to load restricted
medications. If the
dispenser is being used for an opioid, the Authorization Code restricts the
Reusable Drug
Dispenser 16 to only being opened by a healthcare professional authorized to
handle opioid
prescriptions in order to load a replacement opioid Drug Cassette 18,
decreasing opioid
divergence. A USB cable is required to open the Reusable Drug Dispenser 16.
When a USB
cable is plugged in to power the locking and unlocking of the Reusable Drug
Dispenser 16
Microactuator 1028, the Authorization Code must be entered to open the
Reusable Drug
Dispenser 16.
[000403] Once opened, the individual loads the Drug Cassette 18 containing
the opioid into
the Reusable Drug Dispenser 16 and then checks to ensure that the Opioid
Specific App 12
recognizes the Reusable Drug Dispenser 16 and that the Reusable Drug Dispenser
16 is ready to
dispense the medication. If it is a new prescription, the Opioid Specific App
12 is immediately
ready to dispense the medication with the authorized Biometric Authentication
850 and Patient 6
response information 862, 864, 866. If it is a refill for an existing opioid,
the Opioid Specific
App 12 will authorize dispensing the medication per the prescription upon
Biometric
Authentication 850, input of the requisite information, and checking to ensure
the prescribed 4
opioid has not been previously dispensed using a different Drug Dispenser 16.
This eliminates
duplicate dosing of an authorized opioid dose.
[000404] If for any reason the Opioid Specific App 12 does not recognize
the Drug Dispenser
16 or the drug is not the specified opioid, the Opioid Specific App 12 will
show an alert and
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present the issue so that it may be resolved. A click on the Alert Screen on
the interface device
14 connects the individual with the Integrated Support Center 22. For
Standalone Drug
Dispensers 16 that do not have a phone capability, the advisory presents the
number to call to
obtain support.
[000405] When the Opioid Specific App 12 recognizes the Reusable Drug
Dispenser 16 and
the opioid in the Drug Cassette 18 as being a refill for a prescribed drug,
the Opioid Specific App
12 checks to see if the medication in the first drug cassette was fully
dispensed. If it has not been
fully dispensed, then the medical professional loading the Drug Cassette 18 is
advised that: 1) the
second Drug Cassette 18 for the same drug will not be allowed to begin
dispensing of the
medication until the doses in the first Drug Cassette 18 have all been
dispensed, or 2) that the
ability to dispense from the first or previous Drug Cassette 18 will be
blocked and that the
medical professional should discard the first Drug Cassette 18. The
replacement of a Drug
Cassette 18 before it is fully consumed per the authorized Prescription 4 is
noted in the Central
Servers 10 to assist in tracking potential opioid divergence. The alert also
provides requisite
troubleshooting/reset instructions designed to ensure that a given patient
cannot dispense more
opioid within a specified period of time than is allowed by the Prescription
4, regardless of the
number of Drug Dispensers 16 containing the prescribed medication the Patient
6 may have.
[000406] When ready, the ready to dispense screen appears. Then, if the
Drug Cassette 18 is
being loaded by a medical professional, the individual will provide the
Patient 6 the closed,
loaded, and locked tamper resistant Drug Dispenser 16 containing the
prescribed opioid in the
Drug Cassette 18 with the related package insert, prescription and patient
instructions much the
same as with any other prescription.
[000407] Dispensing the Disposable Drug Dispenser
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[000408] In the case of a Disposable Drug Dispenser 16, dispensing only
requires that the
Pharmacy 8 dispenses the opioid much the same as any other prepackaged
medication. The
Opioid Specific App 12 will effectuate a handshake with the Disposable Drug
Dispenser 16 and
automatically preclude double dispensing the same prescribed opioid dose from
more than one
Drug Dispensers 16 simultaneously. The Opioid Specific App 12 ensures that all
dispensing is
restricted per the Prescription 4 instructions.
[000409] Once recognized by the Opioid Specific App 12, the App 12 logs the
Drug
Dispenser's 16 unique serial number, Drug Cassette's 18 unique serial number,
the medication's
NDC number, opioid batch number, opioid's expiration 458 and Prescription
Expiration Date
103 (beyond-use date), and unique storage parameters 460, 462 etc. Thereafter,
the Opioid
Specific App 12 will not dispense the prescribed opioid, e.g., oxycodone, from
other than from
authorized Drug Dispensers 16. No duplicate dosing will be allowed to occur.
[000410] Closed Loop Tracking
[000411] The integrated system enables a closed loop tracking of the opioid
which includes
the Prescriber 2, the Prescription 4, the Patient 6, the Pharmacy 8, Data
Servers 10, Opioid
Specific App 12, Interface Device 14, Drug Dispenser 16, Drug Cassette 18, and
if applicable,
the RFID Pill 20, and or Selfie 21 capturing the Patient 6 ingesting the pill.
The opioid can be
tracked from the time the Drug Cassette 18 is filled with the opioid until it
is dispensed or
ingested.
[000412] Patient Values
[000413] Ensuring the proper utilization of an opioid, such as OxyContin ,
serves as an
example of how the embodiment can be used to ensure medication efficacy,
proper opioid
utilization and the avoidance of medication mediated adverse events, overdose,
abuse, misuse,
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under dosing, over dosing, addiction, dependence, and adverse drug-drug
interactions. They can
be utilized for medication titration, withdrawal, prevention of side effects
(e.g., opioid induced
constipation), and better patient management by capturing certain drug related
side effects. The
information can also be utilized to capture patient reported outcomes (PRO)
information required
during clinical trials for regulatory agency submissions.
[000414] The information that is captured is medication and/or Drug
Specific Dispensing
Algorithm 13 dependent. As an example, the CDC recommends that physicians
assess pain
using validated instruments such as the 3-item (PEG) Assessment Scale, which
can be
incorporated by the embodiment of the invention, on a scheduled basis for
reporting to the
appropriate healthcare professionals, subject to Patient 6 approval:
1. What number best describes your pain on average in the past week? (from
0 = no pain to
= pain as bad as you can imagine)
2. What number best describes how, during the past week, pain has
interfered with your
enjoyment of life? (from 0 = does not interfere to 10 = completely interferes)
3. What number best describes how, during the past week, pain has
interfered with your
general activity? (from 0 = does not interfere to 10 =completely interferes)
[000415] Examples of values that may be tracked by the Opioid Specific App
12 to assist the
Drug Specific Dispensing Algorithm 13 in making opioid dispensing decisions
and/or to assist
the Prescriber 2 in managing the Patient 6 include but are not limited to: (i)
a decreased oxygen
saturation level (Sp02) as a result of opioid induced slow and/or shallow
breathing, (ii) a rapid or
very slow heart rate, (iii) compromised cognition, (iv) slurred and/or changed
speech pattern, (v)
miosis, and/or (vi) weight loss. An excellent example of an avoidable side
effect is constipation.
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[000416] One common approach to non-invasive pulse oximetry that can be
incorporated into
an Interface Device 14 uses a dual-wavelength sensor placed across a section
of venous tissue
such as the patient's digit (placed over the sensor) to measure the percentage
of hemoglobin
oxygenated in the arterial blood, and thereby measures the patient's oxygen
saturation level. In
addition, since the oxygenated hemoglobin at a specific tissue position is
pulsatile in nature and
synchronous with the overall circulatory system, the system indirectly
measures the patient's
pulse rate. A low Sp02 is indicative of hypoxemia which may result from very
slow and shallow
breathing caused by too much opioid.
[000417] For detection of potential respiratory depression associated with
the administration
of narcotic analgesics, such as OxyContin , oxycodone, hydromorphone,
hydrocodone,
morphine, etc., a system which indicates a patient's respiratory and cardiac
status without the
need to invasively measure or sample the patient's blood is particularly
desirable and useful.
Today, these are available as Apps on smartphones and on real time fitness
monitoring devices,
e.g., FitBit, Jawbone, and Fuelband, etc. As an example, both (i) non-
invasive pulse oximetry to
monitor blood oxygen saturation, and (ii) pulse rate are now becoming readily
available on
smartphones (e.g., Samsung's Galaxy 6 S and 7 S with an S Health App that has
a pulse, heart
and oxygen saturation monitor, similar Apps for Apple's iPhone, iOximeter,
etc.) and wearable
diagnostic and/or monitoring devices. The embodiment has the ability import,
for example,
oxygen saturation and heart rate values from these devices through the
development of APIs
(application program interfaces).
[000418] Sp02 can thus be measured as a Self-Test 84 on the Interface
Device 14 and/or via
digital capture from another App 852, 858, 859, 860 and or digitally captured
values from an
oximetry device 882.
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[000419] Heart rate can be digitally captured on an ongoing basis by a
Digital Monitor 859
and/or as a Self-Test 864.
[000420] Compromised cognition may be indicated by a manual dexterity
reflex Self-Test
864. The result is then compared to base and trended values to ascertain the
Patient's 6 changes
in cognition.
[000421] A slurring and volume Self-Test 864 can be utilized to recognize
changes in speech
pattern. The result is then compared to base and trended values to ascertain
the Patient's 6
changes in speech and volume. An IBM Watson tone test can be utilized by the
Integrated
Support Center 22 to listen to the Patient 6 when they call as an input to
making a decision of
whether or not to allow the Patient 6 to dispense an opioid dose that has been
disallowed by the
Opioid Specific Dispensing Algorithm. A two-way video conference can be
utilized by the
Integrated Support Center 22 to utilize IBM Watson's facial recognition
software to use the
Patient's 6 face in comparison to meta data facial comparison learning to
ascertain if the Patient
6 is potentially overdose or borderline to educate any call center decisions,
etc.
[000422] A miosis Self-Test 864 can be carried out by having the Patient 6
take a selfie of
his/her eye or face. The result is then submitted to the appropriate light
adjustment algorithm
and the miosis measurement is then compared to base and trended values to
ascertain the
Patient's 6 changes in pupil constriction in order to ascertain if excessive
constriction of the
pupil is occurring which may be the result of opioid over dosing. The Iris
Scan biometric can be
utilized to automatically capture the pupil scan.
[000423] Weight loss can be tracked using a digital scale 858 either
through digital capture
via an API, from a Digital Interface 860, and/or through Self-Reporting 866.
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[000424] Utilization of Self-Reporting 866 regarding stool consistency,
e.g., using the Bristol
Stool Index, and frequency of bowel movements can indicate when the patient
may be moving
towards opioid induced constipation and enable preventative use of the
prescribed laxative.
[000425] Tracking of certain drug related side effects via self-assessment
862, self-test 864,
and/or self-reporting 868 can assist the Prescriber 2 in managing certain
Patients 6.
[000426] Digitally or self-reporting tracking of medications taken by the
Patient 6 since they
took their last opioid dose can decrease the potential of drug-drug adverse
events, overdoses.
[000427] A myriad of factors can interfere with how the medication is
metabolized and alter
the need or effectiveness of the drug over time. Continual monitoring as the
Patient 6 takes the
opioid enables tracking of trends to ensure the opioid continues efficacious
for the patient and to
monitor and manage any changes in patient medication tolerance, etc.
[000428] Dispensing
[000429] Information capture is of little value if it is not actionable.
The Drug Specific
Dispensing Algorithm 13 is designed to incorporate certain drug specific
values to make a
dispense or do not dispense decision, even if dispensing would otherwise be
authorized by the
prescription. This enables personalization of each medication prescription 4
to the individual
Patient 6, significantly improving the medication's efficacy/safety profile.
[000430] Under the embodiment, the patient would be prescribed an opioid
in: (i) a
Disposable Drug Dispenser 16 containing the specified opioid, or (ii) the Drug
Cassette 18 to be
loaded into the Reusable Drug Dispenser 16 by a medical profession and
dispensed to the Patient
6 using the Opioid Specific App 12 controlled Reusable Drug Dispenser 16 with
the Drug
Cassette 18 docked in the tamper proof unit. When the Patient 6 clicks on the
Opioid Specific
App 12 to take his/her next dose, the Drug Specific Dispensing Algorithm 13
would
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automatically check to ensure the drug has not expired 542, and if it has not,
then to see if the
opioid has been stored within opioid specific temperature 558 and humidity
ranges 566, and if
the Drug has been stored correctly, then it would check the Prescription 4 to
ascertain when the
Patient 6 may take his/her next dose 580, 584, 588, and, thereafter, it would
handshake with
designated devices to digitally capture, for example, the Patient's 6 heart
rate (to see if it is slow
and erratic), weight information (to see if the Patient 6 is losing weight),
etc. Thereafter, it asks
the Patient 6 at least one Patient Self-Assessment 862, Patient Self-Test 864,
and/or Patient Self-
Report 866 question by bringing up the respective screen(s). An example of a
Patient Self-
Assessment 862 screen is the Patient's 6 pain level using the Wong-Baker FACES
scale.
Examples of the Self-Test 864 screens may include: (i) a Motor Skills Test to
ascertain
cognition, (ii) a self-administered peripheral capillary oxygen saturation
(Sp02) test to estimate
the amount of oxygen in the blood as an indicator of potential hypoxia which
may be caused by
opioid induced respiratory depression, (iii) the Patient 6 taking a selfie of
his/her eye or face
(with her/his eyes open) to ascertain if his/her pupils are excessively
constricted, possibly due to
opioid over dosing, (iv) a speech print to ascertain if the Patient 6 has
slurred speech, a change in
how quickly the patient talks, and/or a change in normal volume, etc. Examples
of Patient Self-
Reporting 866 include but are not limited to: (i) stool composition, using a
scale such as the
Bristol Stool Scale, to ascertain if the patient may be getting constipated
(possible opioid induced
constipation), (ii) a bowel movement frequency screen to ascertain any changes
in bowel
movement that may be indicative of becoming constipated, (iii) a query
regarding the new or
altered use of medications which may interact with the opioid, etc.
[000431] The Drug Specific Dispensing Algorithm 13 can use any combination
of digitally
captured 852, 854, 856, 857, 858, 859, 860, 880, 882, 884, 886, Self-
Assessment 862, Self-Test
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864, Self-Report 866 physiological, psychological, lifestyle, other
medications taken, and
environmental data to make the dispense 868 or do not dispense 870, 872, 874
decision. The
data capture can be the same every time the Patient 6 wants to dispense a dose
or (i) the data
request may be triggered by a cascade of information where a value within a
specific range, e.g.,
heart rate, can precipitate the request for a specific input, e.g., a Sp02
Self-Test 864, or (ii) the
data screens may be presented on the Interface Device 14 at pre-determined
intervals, e.g., every
so many dispenses, at predefined time intervals, if a value on another screen
falls within a
predefine range or if the Patient 6 answers a specific question in a certain
way, etc.
[000432] As an example, after Biometric Authentication 850, the Opioid
Specific App's 12
Drug Specific Dispensing Algorithm 13 uses a Decision Tree, see FIG. 11
through FIG. 16.
The algorithm can be as simple as using an Iris Scan for the biometric logon
and then using light
adjusted and trended Iris scan data to measure the pupil size and compare it
to baseline values to
ascertain if the Patient 6 has excessive constriction of the pupil of the eye
which may be an
indication of opioid over dosing or potential over dosing if another dose is
taken. If the Iris scan
is within an acceptable range, the algorithm could: (i) present the Wong Baker
FACES scale to
track the Patient's 6 pain over time (or skip this step), and /or (ii) go to
the Ready to Dispense
868 screen ¨ allowing the Patient 6 to dispense the dose with a single click
on the Drug
Dispenser's 16 dispensing button.
[000433] Alternatively, it can use, for example, a fingerprint scan. After
authentication, the
algorithm can begin capturing Patient 6 input data by asking the Patient 6 to
click on his/her pain
level, using the Wong Baker FACES , on the first Self-Assessment 862 screen.
The pain level
information is used to track the opioid's efficacy and to provide trending
data to ascertain if the
Patient 6 is developing opioid tolerance. Upon tapping on the respective
value, the algorithm
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automatically presents, as an example, the Sp02 Self-Test 864 screen. Once the
Sp02 Self-Test
864 is complete, the Drug Specific Dispensing App 13 evaluates the trended
Sp02 data to
ascertain if the Patient 6 is or may be moving toward hypoxia. If potential
respiratory depression
is suspected, a cognition Self-Test 864, which would not otherwise be
presented, is automatically
presented. If everything is within acceptable ranges, the Drug Specific
Dispensing Algorithm 13
can present, for example, a constipation Self-Reporting 866 screen, can ask
the CDC
recommended 3 Item PEG Assessment Scale, ask for Prescriber 2 requested side
effect
information, and/or clinical trial PRO data, or go directly to the Ready to
Dispense 868 screen.
At this point, the Patient 6 only needs to click on the Drug Dispenser's 16
dispensing button to
dispense the dose.
[000434] However, if, based upon the Sp02 and cognition trended data, the
algorithm
suspects opioid toxicity (overdose) it can ask for additional confirmatory
information, e.g., a
speech Self-Test 864, a miosis selfie, etc. Once the Drug Specific Dispensing
Algorithm 13 is
satisfied that a potential toxic event is or may occur, it locks the Drug
Dispenser 16 and produces
the respective screen 874 telling the Patient to contact the Integrated
Support Center 22, or talk
with their Prescriber 2 or a physician prior to being able to dispense the
next dose, etc., even if
the dose is within prescribing parameters.
[000435] After talking with the Patient 6, the Integrated Support Center 22
representative can
decide, within their operating constraints, whether to remotely unlock the
Drug Dispenser 16 and
allow the Patient 6 to dispense the opioid. If it does not appear appropriate
to authorize the
Patient 6 to dispense the opioid, the representative can triage 806 the
Patient 6 to an Integrated
Support Center 22 physician or another medical professional. The physician can
change the
Prescription 4, if authorized, and can make the decision whether to unlock the
Drug Dispenser 16
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and allow the Patient 6 to dispense the medication. Whoever, has the last
interface with the
Patient 6, is responsible for: (i) terminating the call with the Patient 6,
(ii) sending a summary
email with instructions 830 to the Patient 6, (iii) updating the patient's
record 818, (iv) advising
the Prescriber 2 that dispensing has been stopped or the Prescription 4
changed 832, and (v)
updating the Electronic Medical Record 24.
[000436] If there is a consultation between the Prescriber 2, the
prescription can be changed
by the Integrated Support Center 22 in the Patient's 6 Opioid Specific App 12
resident on the
Patient's 6 Interface Device 14 or Standalone Drug Dispenser 16 based upon the
Prescriber's 2
instructions.
[000437] The embodiment personalizes opioid treatment, improves the
medication's
drug/safety profile, and enhances the Patient's 6 quality of life all while
decreasing preventable
side effects, accidents, and overdoses and thereby decreasing the number of
physician
interactions and ER visits - saving on the total cost of patient care and
saving lives.
D. Drug Recalls or Clinical Trial Medication Stoppage
[000438] In the event of a drug recall or in the event that a drug is in a
clinical trial, the
Integrated Support Center 22, within its procedures and controls, can remotely
lock all Drug
Dispensers 16 that contain a specified opioid and simultaneously alert the
Patient 6 that he/she
cannot dispense the opioid and what they should do.
E. Titration
[000439] The embodiment of the Invention can also be utilized to assist in
opioid titration.
Titration helps the body adapt to the medication and often reduces common side
effects that can
occur when one begins opioid therapy. The doctor/Prescriber 6 will likely
start with an initial
low dose of the opioid and carefully adjust the dose upwards to adequate
levels. Titration helps
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find the optimal dose to improve daily functioning. For example, the opioid
dosage is increased
slowly to the highest tolerable dose. Once there is no more improvement in
symptoms as the
dosage increases, the Prescriber 6 will lower the dose to the previous one. If
a higher dose
produces too many side effects, the dosage is lowered. Opioids management is
based on an
individual's own personal needs and responses. The optimal dose of opioid is
one in which daily
function is significantly improved and side effects are minimized.
[000440] There are three simple goals for pain management;
(i) A good night's sleep,
(ii) Pain control during the day while at rest and
(iii) Pain control when the Patient 6 is active and ambulatory.
Where there is no previous history of opioid intake, the starting dose is
calculated by assessing
the severity of the pain, patient's age, weight, sex and general physical
condition.
[000441] The invention is designed to enable changes in how opioids are
titrated using a
combination of Oral Patient Controlled Analgesia and, for example, the Wong
Baker FACES 0
to 10 pain Self-Assessment index. The changed therapy would enable the Patient
6 to administer
a low dose opioid as needed within certain waiting times between doses. Once
the Self-Assessed
pain index level reaches a certain level of pain control, the interval between
doses would be
increased until the pain level once again begins to rise. At that point, the
interval between doses
could be decreased back to the previous interval. Review of the data would
allow the Prescriber
2 to increase the prescribed dosage strength to decrease the number of doses
the Patient 6 would
have to take to control his/her pain, etc.
[000442] Pain Assessment
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[000443] Pain assessment and re-assessment after administration of
analgesics or pain
management is regulated in healthcare facilities by accreditation bodies, like
the Joint
Commission. The Joint Commission began setting standards for pain assessment
in 2001 stating
that the route of analgesic administration dictates the times for pain
reassessment, as different
routes require different amounts of time for the medication to have a
therapeutic effect. Oral
immediate release (IR) medications require 45-69 minutes.
[000444] Most pain assessments are done in the form of a scale. The scale
is explained to the
Patient 6, who then chooses a pain score. A rating is taken before
administering any medication
and after the specified time frame to rate the efficacy of treatment. Patients
rate pain on a scale
from 0-10, 0 being no pain and 10 being the worst pain imaginable. A scale
with corresponding
faces, e.g., the Wong Baker FACES, depicting various levels of pain is shown
to the Patient 6
and they select one. Patients who cannot verbalize/comprehend pain scales are
assessed with
different types of scales.
[000445] The embodiment of the invention would allow the pain assessment to
be conducted
over a period of time under actual living conditions. This would give a better
assessment of the
Patient's 6 pain level and enable better pain management.
[000446] Opioid Titration
[000447] The Prescription 4 can be written to allow the Patient 6 to
gradually increase their
dose by prescribing a low dose of opioid and allowing the Patient 6 to
dispense the dose more
frequently or to dispense a defined number of pills. As an example, the
Patient 6 could dose
every so many hours and/or fractions thereof or the Patient 6 could dose more
frequently
throughout the day, e.g., from b.i.d. go to t.i.d, from t.i.d. go to q.i.d.,
from q.i.d. to every two
hours, and from every two hours to q.h. It can also be indicated to allow
double dosing before
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bedtime....and to allow p.r.n. dosing at a point where the pain is under
control based upon
trended patient Self-Assessment 862 data and related decreases in Self-
Reported 866 opioid
induced side effects.
[000448] Once steady state has been achieved, the Prescriber 2 can change
the prescription to
best manage the Patient's 6 pain.
[000449] Titration can be facilitated by the utilization of a special
titration Drug Cassette 18,
18a, 18b, 900 configuration containing more than one strength of opioid.
F. Patient Controlled Oral Analgesia (PCOATM)
[000450] Attributes of the embodiment enable Patient Controlled Oral
Analgesia (PCOATM)
even for medications, such as Oxycontin which are not approved for PRN
dosing. Studies have
shown that patients that can self-medicate as warranted, e.g., PRN with set
prescription
parameters, tend to use less medication, further mitigating potential side
effects.
[000451] While it is generally recommended that analgesic medications for
moderate to
severe pain should be given on a regular schedule, the use of the embodiment
allows for
PCOATM dosing. The Patient 6 can be allowed to dispense a certain number of
pills, not to
exceed a specified amount, during a defined time period. A minimum interval
between doses
can also be set. This can be further restricted to limit the total allowed
dose, over a number of
hours or for a given 24-hour period, be restricted to a dosage limitation.
[000452] PCOATM allows prescribing to manage breakthrough pain while
controlling the
maximum allowable dose. PCOATM would allow for the utilization of an immediate
release
opioid in conjunction with an extended release opioid to address issues with
breakthrough pain.
Conversely, it also allows for the elimination of extended release opioids,
allowing the dosing
schedule to coincide with the Patient's 6 pain.
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G. Diagnostic
[000453] The embodiment of the Invention can also be utilized to assist in
diagnosis. As an
example, there are many different types of pain and different types of
headaches. Patients will
generally begin by self-medicating with over the counter (OTC) analgesics such
as aspirin. As
the pain or discomfort increases, patients increase the number of tablets
taken (i.e., the dosage),
as well as the frequency of self-medication. At a certain point, they go to
their doctor seeking
adequate relief.
[000454] When the doctor talks with the Patient 6, he/she may describe many
different types
of pain, making it difficult to diagnose. Pain has multiple causes, and people
respond to it in
multiple and individual ways. The pain that one person pushes their way
through might be
incapacitating to someone else.
[000455] Headaches represents an example. It is important to figure out
what type of
headache is causing the pain. If the doctor knows the type of headache, he/she
can treat it
correctly. However, as was highlighted by a 2004 study, 80% of people who had
a recent history
of self-described or doctor-diagnosed sinus headache, but no signs of sinus
infection, actually
met the criteria for migraine. The following discusses the different types of
headaches:
1) Tension headaches, the most common type of headache, can generally be
adequately treated with over-the-counter treatments such as aspirin,
ibuprofen, or acetaminophen
(Tylenol). Experts believe these may be caused by the contraction of neck and
scalp muscles
(including in response to stress), and possibly changes in brain chemicals.
2) Cluster headaches, which affect more men than women, are recurring
headaches
that occur in groups or cycles. They appear suddenly and are characterized by
severe, debilitating
pain on one side of the head, and are often accompanied by a watery eye and
nasal congestion or
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a runny nose on the same side of the face. During an attack, people often feel
restless and unable
to get comfortable; they are unlikely to lie down, as someone with a migraine
might. The cause
of cluster headaches is unknown, but there may be a genetic component. There
is no cure, but
medication can cut the frequency and duration.
3) Sinus headaches occur when a sinus becomes inflamed, often due to an
infection.
They can generally be diagnosed by symptoms or the presence of pus viewed
through a fiber-
optic scope. Headaches due to sinus infection can be treated with antibiotics,
as well as
antihistamines or decongestants.
4) Rebound headaches, ironically, can be caused by the overuse of
painkillers for
headaches. Culprits include over-the-counter medications like aspirin,
acetaminophen (Tylenol),
or ibuprofen (Motrin, Advil), as well as prescription drugs.
5) Migraine headaches can run in families and are diagnosed using certain
criteria: (i)
at least five previous episodes of headaches, (ii) last between 4-72 hours,
(iii) at least two out of
four headaches have one-sided pain, throbbing pain, moderate-to-severe pain,
and pain that
interferes with, is worsened by, or prohibits routine activity, and (iv) at
least one of the following
is associated with the pain: nausea and/or vomiting, or, if those are not
present, then sensitivity to
light and sound. A migraine may be foreshadowed by aura, such as visual
distortions or hand
numbness. (About 15 percent to 20 percent of people with migraines experience
these.)
6) Mixed headache syndrome, also called transformed migraines, is a
combination of
migraine and tension headaches.
7) Acute headaches are headaches that occur suddenly and have symptoms that
subside after a relatively short period of time.
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8) Hormone headaches are often associated with women's changing hormone
levels
during menstruation, pregnancy, and menopause. Chemically induced hormone
changes, such as
with birth control pills, also trigger headaches in some women.
9) Chronic progressive headaches, also called traction or inflammatory
headaches, are
chronic progressive headaches that get worse and happen more often over time.
These are the
least common type of headache, accounting for less than five percent of all
headaches in adults
and less than two percent of all headaches in kids. Chronic progressive
headaches may be the
result of an illness or disorder of the brain or skull.
[000456] Diagnosis requires a headache evaluation that includes: (i)
headache history, (ii)
description of the headaches, (iii) headache symptoms, (iv) characteristics,
(v) a list of things that
cause the headache, (vi) aggravate the headache, and (vii) things the patient
has done to relieve a
headache. The patient is also requested to keep a headache diary.
[000457] The proper treatment will depend on several factors, including the
type and
frequency of the headache and its cause. There are many migraine and headache
medications
and other treatments are available. The appropriate treatment often depends on
the type of
headache.
[000458] Headache pain may need to be managed with medications. Headache
drugs used to
treat headache pain can be grouped into three different categories:
symptomatic relief (drugs
used to treat the headache pain or accompanying symptoms of migraines like
nausea), abortive
therapy (drugs used to stop a migraine headache), and preventive therapy
(drugs used to prevent
a migraine). Botox injections represents another migraine and headache
treatment.
[000459] The way the body responds to migraine and headache medications may
change over
time, so medications may need to be adjusted.
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[000460] The embodiment of the Invention enables the aggregation of Patient
6 specific
dispensing information and Patient Self-Assessment 862 and/or Self-Reported
866 information
specifically developed to assist in the diagnosis and management of headaches.
H. Management of Complex Drug Therapy
[000461] The embodiment includes the use of a Multidrug Drug Dispenser
1002, 1004, 1006,
1008 in conjunction with a Consolidation Therapy App 1000 that would allow for
the dispensing
and control of two or more medications to better manage complex drug
therapies. As an
example, to dispense a long acting opioid, an immediate release opioid, and a
medication or
medications to address opioid induced side effects when certain Self-
Assessment 862, Self-
Testing 864, Self-Reporting 866 or digitally captured information indicates
the symptomatic
medication is warranted to treat the side effect, e.g., diarrhea and vomiting.
I. Opioid Concerns
[000462] Opioids (examples include: codeine, fentanyl and analogs,
hydrocodone,
hydromorphone, methadone, oxycodone, Oxymorphone, etc.) are effective in
controlling pain.
However, physicians are reluctant to prescribe them due to their overdose,
abuse, addiction and
divergence potential and related REMS programs. Some patients are also
reluctant to take them
due to their addiction potential. The embodiment provides control and real
time monitoring and
thereby address opioid shortcomings.
[000463] Overdosing is addressed by: 1) a diagnostic screening diagnostic
that precludes
dispensing an opioid dose if there is an indication the Patient 6 is overdosed
or would likely
overdose if the Patient 6 takes another opioid dose, even if the dose would be
authorized by the
Prescription, and (ii) the inability of the patient to dispense a dose more
frequently than allowed
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by the Prescription 4. This is handled by the Drug Specific Dispensing
Algorithm 13 which
controls dispensing by the Drug Dispenser 16.
[000464] Abuse is addressed by the design of the tamper resistant Drug
Dispenser 16. For
Reusable Drug Dispensers 16, The Drug Specific Drug Cassette 18 can only be
docked with the
Reusable Drug Dispenser 16 by an authorized medical professional. Any attempt
by an
unauthorized person to open the Drug Dispenser 16 triggers a signal to the
Opioid Specific App
12 which automatically locks the Drug Dispenser 16 and alerts the Integrated
Support Center 22.
Alerts are also generated if the Patient 6 is trying to use multiple Drug
Dispensers 16 to double
dose. When the Integrated Support Center 22 is alerted, it then calls the
Patient 6 to ascertain
why he/she is trying to open the Drug Dispenser 16 and/or trying to dispense
duplicate doses. At
this point, the Integrated Support Center 22 works with the Patient 6 to
address any dispensing
related issues and can unlock the Drug Dispenser 16 so a dose can be dispensed
or, if attempted
abuse is suspected, contacts the Prescriber 2 to alert them of the
conversation with the Patient 6
and asks the Prescriber 2 whether the Drug Dispenser 16 should remain locked
so no opioid can
be dispensed or if it should be unlocked to allow dispensing. If authorized,
the Integrated
Support Center 22 updates the Electronic Medical Record 24 related to the
calls to the Patient 6
and the Prescriber 2.
[000465] Addiction potential is deceased by: (i) the patient's inability to
dose more
frequently than the prescribed medication schedule, regardless of the number
of Drug Dispensers
16 that contain the opioid that the Patient 6 has, (ii) by tracking attempted
earlier than prescribed
dosing events to enable early intervention, (iii) by capturing any attempts to
open the Drug
Dispenser 16, and (iv) through the use of patient Self-Assessment 862, Self-
Testing 864, Self-
Reporting 866 and/or digitally captured relevant information 852, 854, 856,
857, 858, 859, 860,
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880, 882, 884, 886 trended over time, to ascertain the effectiveness of the
opioid in controlling
the Patient's 6 pain. The centralized drug specific patient and population
focused analytics
programs on the Data Servers 10 are designed to use data analytics, on
individual as well as
metadata from all Patients 6, data captured by the Opioid Specific App 12 to
identify potential
movement of the Patient 6 toward addiction. When potential addiction is
identified, the analytics
software alerts the Integrated Support Center 22 so they may alert the
Prescriber 2 and update the
patient's 6 Electronic Medical Record 24. The more data collected and analyzed
the more
accurate the predictive analytics will be.
[000466] Divergence is decreased by: 1) the tamper resistant Drug Dispenser
16 design
which triggers an alert if unauthorized attempts to open the Drug Dispenser 16
are sensed, 2)
restriction of Drug Cassette 18 docking into the Reusable Drug Dispenser 16 by
authorized
medical professionals, 3) restricting access to the opioid except for single
dispensed doses
dispensed per the Patient's 6 prescription 4, 4) precluding dose dispensing to
a single dose
regardless of the number of Drug Dispenser's 16 the Patient may have, 5) the
automated closed
loop opioid tracking system that: (i) correlates the serial number of the Drug
Specific Drug
Cassette 18 and the drug's batch number to the Drug Dispenser 16, (ii) the
serial number of the
Drug Dispenser 16 is linked to the Patient's 6 Opioid Specific App 12, (iii)
the use of the Opioid
Specific App 12 is restricted to a specific Patient 6, and (iv) the Opioid
Specific App 12 requires
a biometric login 850 to access the Opioid Specific App 12 in order to
instruct the Drug
Dispenser 16 to dispense the opioid. Furthermore, additional control is
supplied if the drug
being taken can be tracked with RFID 856 tracking until ingested and/or a
Selfie 857 is taken
confirming the opioid dose was in fact taken by the Patient 6. The time
interval between the
time the drug is dispensed and the time it is ingested, over time, provides an
indication of
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compliance, dose stockpiling, or divergence. When coupled with metadata
analytics conducted
by the Data Servers 10, the probability of accurately identifying potential
abusers and divergence
is significantly increased.
[000467] Side Effects - The system may also be utilized to predict
potential side effects. For
example, opioid related constipation can be predicted based upon the Self-
Reporting 866 of the
frequency of bowel movements since the previous dose or over a previous
specified time period
as well as the stool consistency of the last bowel movement, etc. If
predicted, the Opioid
Specific App 12 can alert the Patient 6 to take a laxative at the appropriate
time. If a multi-drug
Drug Dispenser 1002, 1004, 1006, 1008 is utilized, the Consolidated Therapy
App 1000 can
dispense the laxative as well as the opioid and/or other medications as
prescribed.
[000468] REMS - The system is designed to comply with the respective REMS
program and
to virtually eliminate required data capture and automate patient specific
tracking and dispensing
report preparation. The Integrated Support Center 22 also supports the
Prescriber 2 by preparing
the required REMS reports encompassing all his/her patients.
[000469] Prescription Drug Monitoring Programs - The system also allows for
the
redefinition of Prescription Drug Monitoring Programs by closing the loop
between the
Pharmacy 8, the Prescriber 2 and the Patient 6 by controlling and tracking use
on an individual
Patient 6 and Prescriber 4 and dispensing Pharmacy 8 basis.
J. Addiction and Withdrawal Treatment
[000470] Addiction is a global crisis. As an example, there are an
estimated 2.4 million
opioid-dependent people in United States, 1.3 million in Europe and twenty
million in the rest of
the world. Opioid overdose is the second leading cause of accidental death in
the United States.
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According to the CDC, overdoses from prescription opioids claimed over 18,000
lives in the
United States alone in 2014.
[000471] Opioid addiction can either be treated with buprenorphine and/or
naloxone
(examples of brand names include Butrans, Suboxone, Zubsolv). In cases of
physical
dependence, withdrawal must be managed through the gradual decrease of opioid
doses of the
dependent drug.
[000472] Appropriate precautions must be taken to minimize risk of misuse,
abuse, or
diversion, appropriate protection from theft, and unintended pediatric
exposure. In addition,
appropriate clinical monitoring as to the Patient's 6 level of stability is
essential. The
embodiment of the system provides dispensing control and real time monitoring
and thereby
address each of these shortcomings.
[000473] Decreased dosing for the treatment of addiction and withdrawal
utilizes all the
features of the embodiment and is controlled by the Prescription 4.
K. Clinical Trials
[000474] The system is designed to capture, store, analyze, and act upon
drug specific patient
self-assessment 862, self-testing 864, self-reporting 866 and digitally
captured 850, 852, 854,
856, 857, 858, 859, 860, 880, 882, 884, 886 physiological, psychological,
lifestyle, other drugs
currently being taken, and environmental information along with the drug's
Prescription 4 and
drug dispensing and Drug Dispenser 16 storage history in order for the Opioid
Specific App 12
to decide if the medication should or should not be dispensed. Dispensing can
be precluded by
the Opioid Specific App 12 based upon defined clinical trial guidelines as
well as the
Prescription 4. In this way, patient monitoring information can be utilized to
preclude dispensing
a prescribed dose if a potential adverse event is identified.
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[000475]
Most of the time, clinical outcomes are held as the ultimate outcome in a
clinical
trial because they often provide more objective interpretation, increased
reliability and greater
simplicity of interpretation. However, certain disease conditions require
consideration of
subjective outcomes. Regulatory agencies, such as the FDA, are combining
patient reported
outcomes (PROs) and clinical outcomes in their approval decisions. Examples
include the: (i)
FDA's "Guidance for Industry, Irritable Bowel Syndrome ¨ Clinical Evaluation
of Drugs for
Treatment", dated May 2012 and (ii) the European Medicines Agency (EMA)
"Guideline on the
evaluation of medicinal products for the treatment of irritable bowel
syndrome" dated April
2015. They utilize a combination of PROs and patient self-assessment reporting
to measure
primary and secondary endpoints required for regulatory approval of any 5HT3
drugs for
irritable bowel syndrome (IBS).
[000476]
Interest in developing and applying patient-reported outcomes (PROs) across
the
drug development and postmarket spectrum is growing¨among sponsors,
clinicians, payers,
regulators and patients. A growing number of clinical trials now are going
beyond conventional
randomized control measurements to collect self-reported outcomes from
patients¨focusing on
improving patients' involvement by including their perspectives throughout the
drug
development process.
An analysis of sponsor-funded interventional studies listed on
CenterWatch's Clinical Trials Listing Service found between 2005 and 2007,
only 6.1% of total
study procedures involved some type of subjective outcome assessment. That
grew to 11.8% in
the 2008 to 2010 timeframe and, most recently, between 2011 and 2013,
increased to 16.3% of
total study procedures. PROs can capture a range of information, from symptom
changes and
level of functioning, to health-related qualify of life and treatment
satisfaction and adherence.
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[000477] Although their value is widely recognized, PRO use often is
inconsistent and
underutilized in understanding how patients feel in relation to their
diseases, such as cancer,
cardiovascular disease, diabetes, etc. Generally, regulatory agencies do not
require sponsors to
consider PROs in clinical trials and, until recently, did not do much to
encourage their use.
However, signs point to that sentiment is changing. Janet Woodcock, M.D.,
director of the
FDA's Center for Drug Evaluation & Research (CDER) stated: "We understand that
people with
chronic diseases are experts in that disease, as far as the symptoms and the
impact on quality of
life, and what might be acceptable tradeoffs on risk and uncertainty. The
challenge for the FDA
is incorporating that knowledge in a way that accurately informs regulatory
decisions." She
asked, "how can we meaningfully collect that knowledge in a rigorous manner,
given there's a
spectrum of opinions and a spectrum of disease burden in any given disease?"
PRO
measurements often are used to evaluate products that treat chronic, disabling
conditions, for
which the goal of treatment is focused on alleviating the frequency, severity
or duration of
disease symptoms.
[000478] PROs generally are used as primary endpoints in clinical trials in
indications such
as migraines and irritable bowel syndrome, in which specific symptoms, such as
pain, play a
major role in treatment. PROs also are important in the final product labeling
manufacturers are
allowed to use to promote their products, and to clinicians seeking
information to support their
prescribing choices. Now, trials for psychiatric and age-related illnesses,
among others, are
including PROs as part of the protocol design.
[000479] Pain studies initially used PROs as a primary outcome in a
clinical trial because
attempts to obtain an objective measure of pain through a dolorimeter, a
spring-loaded
instrument with a gauge for measuring sensitivity to, or levels of, pain, or
through a galvanic
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skin response lacked validity compared to simple pain scales. Other disease
examples where
PROs are preferable include neurology, depression, anxiety, and irritable
bowel syndrome (IBS)
which may utilize co-primary and/or key secondary PROs.
[000480] Keeping trial participants involved also is the hallmark of the
publication and
promotion of the FDA's PRO guidance at the end of 2009. In 2011, the FDA took
the next step,
seeking multiple ways to give the patient a clear voice in clinical research
by ensuring all
measurements and outcomes reflect what is happening with the patient through
instruments or
tools, along with PROs. Increasingly, we are seeing patients in clinical
trials demanding to know
what is going on and they want to be given a greater voice.
[000481] Generally, larger clinical sites can handle adding PROs more
easily, while smaller
sites, especially in more remote locations, can find it more challenging.
Collecting data directly
from the patient can provide stronger information. As an example, patients can
be hesitant to
report outcomes if they have been asked to take a medication a certain way and
have not done so.
[000482] Furthermore, collecting data through specific data streams
provides, in some cases,
better quality. Patients will contact the independent group, such as the
clinical trial CRO or in the
embodiment, the Integrated Support Center 22, and not necessarily go back to
their physicians
for technical issues and concerns.
[000483] While using PROs is becoming critical in many clinical trials to
prove safety and
effectiveness to gain FDA approval, the next step for biopharmaceutical
companies and payers
will be to combine PROs with other observational studies to create real world
evidence (RWE).
RWE is becoming essential for sound medical coverage, payment and
reimbursement decisions,
according to the International Society for Pharmaeconomics Outcomes Research
Real-World
Data Task Force. RWE can be used with randomized clinical trials to design
more efficient trials
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and understand a drug's benefit-risk profile, as well as to gain understanding
of the market for
launch planning, according to the task force. RWE shows how a drug is accepted
from Patients
6 who have experience using it. It reveals how a drug is utilized in different
geographies and can
be used to help frame policy or regulatory decisions. It is a highly credible
source of
information.
[000484] The embodiment provides: (i) the requisite data capture, (ii)
Patient 6 involvement,
(iii) dispensing control, (iv) avoidance of certain drug related side effects,
(v) real time reminders
for the Patient 6 to take the medication, (vi) intervention alerts if the
Patient 6 fails to take their
medication within a predefined time interval, (vii) dispensing tracking (date
and time), (viii) if an
RFID chip is integrated, time of ingestion, (ix) if a Selfie is taken,
confirmation of ingestion, (x)
real time monitoring, and (xi) reporting. It addresses the shortcomings of
current systems to
capture and compile real time, Patient 6 and drug specific data to facilitate
ongoing clinical trial
data aggregation, analysis, and reporting while minimizing the number of calls
to the clinical
trial physician.
[000485] Under the current embodiment, the Patient 6 would be prescribed
the opioid to be
dispensed per a defined prescription using the Opioid Specific App 12
controlled Drug Dispenser
16. When the Patient 6 clicks on the Opioid Specific App 12 to take his/her
next dose, the Drug
Specific Dispensing Algorithm 13 automatically handshakes with the Drug
Dispenser 16,
handshakes with defined digital devices (e.g., blood pressure, heart rate,
etc.) FIG. 18, FIG. 19
and downloads the latest data to the Interface Device's 14 Opioid Specific App
12 data base,
checks to ensure the drug has not expired 458, and if it has not, then to see
if it has been stored
correctly 460, 462. If the Drug has been stored correctly, then, for example,
it automatically
moves to the next screen and asks the Patient 6 to answer the specific
questions. In this example,
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the Patient 6 would answer the PRO and data capture screens 862, 864, 866
required by the FDA
and EMA to get approval for the opioid with expanded claims. The ability to
capture the
requisite PRO primary and secondary end-point data and the related compliance
and persistence
data are illustrated in FIG. 18. These screens can be configured to capture
and aggregate drug
specific information.
[000486] The Drug Specific Dispensing Algorithm 13 then utilizes its
decision tree FIG. 11
through FIG. 16 to check the Prescription 4 instructions and when the drug was
last dispensed
464 to ascertain if the drug can be dispensed. It then either generates a
screen stating that the
dose will not be authorized for a specific time period 870 or proceeds to
ascertain if the
designated digital and Patient 6 entered values allow the medication to be
dispensed. If yes, then
the screen shows a green dispense 868 notification and prepares the Drug
Dispenser 16 to
dispense the dose (turns the single click drug dispense button light green
1066). If the Drug
Specific Dispensing Algorithm 13 indicates that the Patient 6 should not
receive the opioid, even
if it is within the Prescription 4 guidelines, then it will either generate,
for example, a screen
stating that the dose is not warranted 870 at the specific time and provide
the Patient 6 the ability
to click on "Dial" to call the Integrated Support Center 22 or if a problem is
ascertained, it will
either show a specifically designed screen or a screen that the Integrated
Support Center 22
should be called 874. The type and sequence of screens is dictated by the
drug's clinical trial
data capture requirements. The algorithm can contain routines that only ask
for specific
information if certain predefined criteria are met.
[000487] Every non-fruitful event to dispense the medication is tracked. At
a certain point
the Drug Specific Dispensing Algorithm's 13 logic will send a message for the
Integrated
Support Center 22 to call the Patient 6.
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[000488] The embodiment allows for better prescription compliance, an
improved opioid
safety profile, increased prescription persistence, uniform data capture,
facilitates data analysis,
decreases required interventions by the clinical trial physician(s), decreases
the cost of the trial,
and provides real time data capture and analysis.
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