HK40002325A - Opioid+device combination products with improved safety and efficacy profiles - Google Patents

Description

Opioid + device combination with improved safety and efficacy profile

Cross Reference to Related Applications

This application claims U.S. provisional patent application No.62/294,585 filed on day 2/12/2016, U.S. provisional patent application No.62/325,012 filed on day 4/20/2016, U.S. provisional patent application No.62/375,192 filed on day 8/15/2016, U.S. provisional patent application No.62/375,256 filed on day 8/15/2016, U.S. provisional patent application No.62/416,972 filed on day 11/3/2016, U.S. provisional patent application No.62/427,919 filed on day 11/30 of 2016, U.S. provisional patent application No.62/432,292 filed on day 9 of 2016, U.S. provisional patent application No.62/432,248 filed on day 9 of 2016, U.S. provisional patent application No.62/432,358 filed on day 9 of 2016, U.S. provisional patent application No.62/432,394 filed on day 9 of 2016, and international patent application No. pct/US16/46491 filed on day 11 of 2016; the entire contents of said patent application are incorporated herein by reference to the maximum extent allowed by law.

Technical Field

The present disclosure relates to a novel system in which each individual component brings unique attributes, together as a drug + device combination product, improving the drug/safety profile of opioids (opioids) and preventing/reducing opioid overdose (overdose), misuse (misuse), abuse (abuse), accidental ingestion (accidental entrance) and opioid emission (divergence). Each opioid drug + device combination product comprises an opioid, interrelated opioid specific and patient customized applications^TM(Opioid Specific and Patient TailoredApp^TM) And overdose diagnosis (OverDoseScreen)^TM) Opioid-specific and patient-customized dispensing algorithms, medication dispensers, kits, electronic data interchange, and some integrated support services. Closed loop systems are designed to reduce opioid transfer (division), misuse, abuse, addiction, dependence, overdose, accidental ingestion and deathDeaths, thereby improving quality of care, improving the quality of life of patients, and reducing overall care costs by minimizing the number of opioid-related medical interventions, emergency room visits, and hospitalizations.

Background

Preventing opioid emission, misuse, reducing the incidence of opioid addiction and dependence, avoiding opioid overdose and death, reducing the incidence of accidental opioid ingestion by children, appropriate dosing (titrating) and administration to patients, optimizing therapy, effectively managing opioid tolerance, avoiding unnecessary opioid-induced side effects, ensuring patient prescription compliance, and controlling opioid withdrawal (withdrawal) represent major unmet needs.

Drug overdose is the leading cause of drug-related deaths in the world, as stated by the United nations drug and crime problem office (UNODC), and opioids are the leading drug types associated with these deaths. The opioid is derived from opium, which is derived from the seeds of poppy. Generally, the term opioid is used to refer to synthetic prescription analgesics, but heroin is also an opioid. The following are commonly used opioids, including the brand names of established products and new products: (i) oxycodone (Oxycodone)(ii) Hydrocodone (Hydrocodeone)(iii) Morphine, (iv) buprenorphine; (v) hydromorphone (Hydromorphone)(vi) Oxymorphone (Oxymorphone)Tapentadol (tapntadol); (vi)i) Tramadol(viii) FentanylMesoximonesMorphine sulfate and naltrexone hydrochlorideOxycodone hydrochloride and naltrexone hydrochlorideAnd the like.

The World Health Organization (WHO) estimates that 1640 ten thousand people use opioids in 2012. People taking prescribed analgesics can become addicted by only one prescription. Once addicted, it is difficult to stop. Opioids are dangerous, as claimed by the National Institute of Drug Abuse (NIDA), in combination with their highly addictive nature, because a single bolus can lead to severe respiratory depression and death. In addition, during discontinuation of drug use, the tolerance of the drug user to opioids decreases. Overdosing usually results when they take the same dose as before the interruption.

North america consume 80% of the world's opioids, as stated by the international bureau of narcotics administration (INCB), and are the countries of the world with the highest drug-related mortality rates. According to IMS Health report, 2014 Americans occupied hydrocodone in the world99% of consumption, oxycodone (C) in the worldAnd) 80% of the consumption accounts for the worldHydromorphone65% of the consumption.

Opioid statistics in the united states are surprising:

a. opioid abuse is a fashion opioid-containing analgesic in the United states as reported by the national drug abuse institute, with about five (5)% of the adult population using opioid-containing analgesics non-medically. In 2015, about 1250 ten thousand people over the past year used the prescribed analgesic, accounting for 4.7% of the population aged 12 years or older¹。

b. The major causes of preventable deaths (e.g., car accidents) have declined, but deaths from drug abuse have doubled over the past decade (two deaths from overdose of prescribed analgesics since 1999). People who die from prescription opioid overdose outnumber those who die from overdose of all other drugs taken together (including heroin and cocaine)². In 2014, there were 18893 cases of excess deaths related to prescription analgesics-52 people per day³. Opioid analgesics are a major cause of accidental death.

In 2015, analgesics recently started to be misused by 210 ten thousand people of 12 years or older (i.e. the first misuse in the past year), with an average of 5753 people per day⁴。

In d.2015, 200 ten thousand people have pain relived pain medication.

e. Most adolescents who misuse prescribed analgesics are freely provided by friends or relatives⁵。

In 2014 467000 adolescents aged 12 to 17 are currently non-medical users of analgesics of which 168000 are addicted to prescription analgesics⁶。

g. According to the CDC, there are nearly 7000 people per day who receive treatment in the Emergency Room (ER) due to the use of opioids in an unindicated manner (equivalent to 260 ten thousand per year, where over 140 ten thousand emergency room visits are associated with prescription drugs).

h. 420000 prescribed opioid overdose emergency room visits per year⁷. Fifty-five percent (55%) resulted in hospitalization (average 3.8 days), costing an average of $ 29500; 45% of the patients received the treatment in the emergency room, with an average cost of $ 3600⁸. The direct medical costs associated with over-visit of ER prescription opioids equate to over 75 billion dollars per year to over 250 billion dollars per year total medical costs (including emergency room costs).

91% of patients with opioid overdose receive another opioid prescription, mostly from the same doctor.

7% of the drug was overdosed within 12 months.

Overdose of 14% again within 24 months.

o 17% of the high dose patients overdose within 24 months, corresponding to 10.7% of the total number of overdose patients taken annually.

i. The medical costs of opioid abusers are almost nine times higher than those of non-abusers.

j. Three studies estimate the economic burden of opioid prevalence in the united states to be about $ 550 million per year.

In the united states, the cost of prescribed opioid abuse in 2007 is about $ 557 billion. Of these, 45% (250 billion dollars) can be attributed to medical costs (e.g., emergency room visits and treatment costs), 46% to workplace costs (e.g., lost productivity), and 9% to criminal jurisdictional costs⁹。

Hansen's research attributed 79% of the costs to lost productivity ($ 420 million), 15% to criminal law costs ($ 82 million), and only 6% to medical costs, of which 4% were used for drug abuse therapy ($ 22 million)Us dollars), 2% for medical complications (us dollars 9.44 million)¹⁰。

In Birnbaum's research, the more widely defined medical costs account for 45% (250 billion dollars) in total, while workplace costs account for 46% (256 billion dollars), and criminal justice costs account for only 9% (51 billion dollars)¹¹. The medical expense figure is associated with the cost per hour estimated above.

Regardless of the cost distribution, the burden on the U.S. medical care system and federal, state, and local governments is enormous and growing.

This is a worldwide problem. For example, canada ranks second, second only to the united states, with respect to the highest per-capita opioid consumption in the world, as stated by the center for substance abuse in canada (CCSA). In europe, death due to heroin is reduced, but death due to synthetic opioids is increased. Estonia is one of the countries in the world where the prescribed opioid death has increased most, increasing by 38% from 2011 to 2012. In new zealand, opioid abuse is increasing, with over 120 million people abusing opioids-primarily prescription analgesics. In south america, a continent known for the production and trade of illegal drugs, opioid abuse is very low in most countries. However, costa rica reported that about 2.8% of the population abused prescription analgesics.

Many problems arise with respect to the abuse of prescription drugs when a physician prescribes highly addicted drugs in too large a dose or drugs based on inaccurate diagnosis. Enhanced review of the physician leads to another problem. Some physicians do not prescribe a sufficiently high dose of the drug because of fear of addicting the patient or because of fear of review by other physicians and/or governmental agencies.

Unfortunately, the people most often suffering from chronic pain are also among the most addictive people. The elderly are among the largest group of prescribed drug addicts in the united states. In 2013, physicians prescribed 21% of 2.6 billion opioid prescriptions for people aged 65 and older, which increased by 20% over the first five years. The drug abuse and mental health service administration (SAMHSA) found that the number of elderly abusing or relying on prescription analgesics increased to 336000 in 2012, and 132000 more than 2002. From 2007 to 2011, emergency room access due to misuse of medications by people over the age of 65 increased by 50%.

One investigation of SAMHSA found: more than half of the 12-year-old and older population abusing the prescription in 2012-2013 freely obtain the drug from friends or family, which exemplifies misunderstanding about prescription safety.

One investigation of NIDA found: about 1 approved non-medical use in every 12 high school students1 of 20 recognized abuses in 2010SAMHSA discovery: 2.2% of 12 to 17 year old adolescents used prescription drugs for non-medical purposes and 1.7% used analgesics for non-medical purposes in 2013. This is more than the sum of hallucinogen (0.6%), cocaine (0.2%) and heroin (0.1%).

Avoiding unnecessary medical complications or deaths by ensuring that the drug is effective for the patient and that the patient's compliance and persistence with their prescription represents a major unmet need and a global market opportunity of billions of dollars-greater than the global pharmaceutical industry. For example, the largest pharmacy stakeholder in the united states Express scales found: only 25% -30% of the medication is taken as prescribed (compliance) and of those users, only 15% -20% is replenished as prescribed (persistence). It is estimated that this lack of compliance and persistence results in a waste of over 3000 billion dollars per year in the united states for the treatment of unnecessary medical complications.

Drug-related hospitalizations account for 2.4% to 6.5% of all medical admissions in the general population. A meta-analysis (meta-analysis) found: hospitalization rates associated with Adverse Drug Events (ADE) were increased four-fold in the elderly (16.6% versus 4.1%) compared to the young. Countless factors in elderly individuals contribute to an increased risk of their developing drug-related problems. These factors include weakness, coexisting medical problems, memory problems, use of compound medications and over-the-counter medications. It is estimated that 88% of ado hospitalizations in the elderly are preventable, while this proportion is 24% in the young.

Opioid overdose of prescription in the United states illustrates the cost saving potential of controlled drug prescription¹². 420000 prescribed opioid overdose emergency room visits and 16000 Rx opioid overdose deaths annually were reported by CDC (center for disease control and prevention). Fifty-five (55)% resulted in an average hospitalization for 3.8 days, with an average cost of about $ 30000. The remaining 45% of patients visited up to an average of $ 3600 per emergency room visit. This equates to an average cost of $ 18000 per ER Rx opioid overdose per year to $ 75 billion total direct costs. If the total medical costs of additional physician visits, addiction treatment, etc. are accounted for, the medical costs (including $ 75 billion) exceed $ 250 billion per year. This estimate has good relevance to other estimates of direct medical costs associated with excessive abuse of prescribed medications.

Optimizing drug therapy is an important part of medical care. The process of prescribing a medication is complex, including (i) deciding to indicate the medication, (ii) selecting the best medication, (iii) determining the dosage and schedule appropriate to the patient's physiological state, (iv) monitoring effectiveness, tolerability, and toxicity, (v) educating the patient for the expected side effects, and (vi) instructing to seek counseling.

Avoidable Adverse Drug Events (ADE) are serious consequences of the following behaviors: (i) an improper prescription for a drug, (ii) a medical condition due to increased tolerance, lifestyle, other drugs, other medical conditions, worsening, patient response to a drug over time, or change in the patient's overall health, etc., or (iii) the addition of new prescription or over-the-counter medications, vitamins, dietary supplements, herbs (e.g., ginseng, ginkgo biloba extract, glucosamine, st. john's swort, echinacea (echinacea), garlic, saw palmetto (saw palmetto), kava (kava), valerian root, etc.), and/or recreational drugs, etc. Clinicians generally do not ask patients for the use of herbal medicines, nor do patients generally provide this information on their own. In addition, most patients do not inform their clinicians that they are using non-conventional and/or recreational drugs. A study using 22 supplements in a survey of 369 60 to 99 year old patients found: of the 22 supplements investigated, there were 10 potential interactions between the supplement and the drug. Thus, any new condition should first be considered drug related unless there is evidence otherwise.

Prescribing the elderly patients who consume the most medications on a person basis presents unique challenges. Pre-market drug trials typically do not involve elderly patients, and approved doses may not be appropriate for elderly people. Many drugs require special precautions to be used due to age-related pharmacokinetic (i.e. absorption, distribution, metabolism and excretion) and pharmacodynamic (physiological effects of the drug) changes.

The larger drug depot and reduced clearance extend the drug half-life and result in increased plasma drug concentrations in elderly people. Great care must be taken in determining the dosage of the drug. The proportional increase in body fat relative to skeletal muscle that is often accompanied by aging can lead to an increase in the volume of drug distribution. Even in the absence of kidney disease, the natural decline in kidney function with age can lead to decreased drug clearance.

The same dose may result in higher plasma concentrations in older patients than in younger patients. For example, in the elderly, the distribution volume of diazepam increases and the clearance of lithium decreases. From a pharmacodynamic perspective, increasing age can lead to increased sensitivity to the effects of certain drugs (e.g., opioids and benzodiazepines). Prescribed opioid overdose death usually involves benzodiazepines.

The use of a greater number of drug therapies is independently associated with an increased risk of adverse drug events (regardless of age) and an increased risk of hospitalization. For the elderly, combination medication is particularly important, and they tend to suffer more from the disease than younger individuals, thus opening up the therapy. About half of the patients taking the medication receive two medications and 20% receive five or more medications. For example, one study found: of the ambulatory elderly with cancer, 84% receive 5 or more medications and 43% receive 10 or more medications.

When taking multiple drugs, the risk of adverse events caused by drug-drug interactions is greatly increased.

The medical regimen for the periodic evaluation of patients is an essential component of medical care. However, one survey for the health insurance beneficiary found: over 30% of patients reported that they did not talk to their physician about their different medications within the past 12 months. Furthermore, when these reviews are complete, they often ignore the over-the-counter medications, supplements, herbs and recreational drugs that patients are taking.

A number of factors contribute to the appropriateness and overall quality of the drug prescription. These factors include: avoidance of inappropriate drug treatment, appropriate use of prescribed drug treatment, monitoring of side effects and drug levels/opioid tolerance, avoidance of drug-drug interactions, monitoring of increased drug treatment tolerance and patient involvement, and integration of patient value perspective. Current measures of prescription quality generally focus on one or some of these factors, but rarely on all.

Summary of The Invention

The present invention describes a novel integrated system comprising an opioid, a tamper resistant drug dispensing device, a related kit, firmware, software, a biometric login, a drug specific and/or patient customized application (App), an opioid overdiagnostic screening (overladosesescreen)^TM) Opioid-specific dose dispensing algorithms, electronic communications, data analysis, and integration support. The systems, processes and methods are integrated together so that they as a whole ensure: 1) opioids are only dispensed or given (or in the case of pre-adults) to patients prescribed opioids (avoid shedding); 2) opioids are effective in patients; 3) appropriate dosing of opioids to obtain the optimal therapeutic dose; 4) opioids are the correct dose to control the patient's pain; 5) the dispensed opioid dose does not overdose the patient, 6) the prescriber has the necessary drug-specific digital capture and/or patient self-assessment and/or self-testing and/or self-reporting of physiological, psychological, lifestyle, concurrent use of drugs, and environmental information (values) to manage opioid administration and/or tolerance and/or side effects; 7) in the case of withdrawal (withdrawing) of a patient's opioids, withdrawal is managed properly; 8) prescriptions are written, filled, and distributed only by authorized medical professionals; 9) the dispensing of each dose is controlled to prevent dispensing if the following conditions are met:

i. the patient attempts to administer the medication earlier than the prescribed interval,

the algorithm concludes that taking the medication may lead to adverse events, such as drug-drug interactions or overdose, even if dispensed in the prescribed dose instructions,

the drug has expired/exceeded the date of use,

the prescribed administration period has elapsed iv,

the drug is not stored properly, e.g., within the appropriate temperature and/or humidity guidelines,

the drug batch has been recalled, and/or

A patient attempts to double a dose or to obtain the same prescribed dose from more than one dispenser at the same time (misuse and/or abuse).

It is intended to improve the safety and efficacy profile of opioids by helping the prescriber manage patient-specific opioid tolerance, opioid-induced side effects (e.g., opioid-induced constipation), and prescription compliance and duration by using self-assessment, self-testing and/or self-reporting information digitally captured at the point of dispensing and/or entered by the patient when dispensing an opioid dose or the patient attempts to dispense. This is a one-time and/or trending information (value) that is provided to the patient and/or prescriber via an on-demand report that shows the relationship between the medication dose and certain follow-up values/side-effect information (e.g., medication effectiveness).

The system functions like the patient's physician asking questions to the patient and making the necessary medication-related observations and dispensing decisions each time the patient attempts to dispense a prescribed opioid dose. In this manner, by increasing the effectiveness/safety profile of the medication, the integrated dispensing system is able to improve the quality of care and the quality of life of the patient while saving money on the healthcare system by: (i) preventing overdose mortality, (ii) emergency room visits, (iii) hospitalization, and (iv) physician and combination healthcare professional intervention, while reducing the incidence of drug-related side effects, addiction, and dependence.

A novel opioid-specific and patient-customized App that can operate 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 assembles the following: (i) prescription information, (ii) medication storage requirements, (iii) the name of the prescriber, a unique identification number issued by the government, and (if applicable) a DEA number (or similar government control number), (iv) medication label information from the cartridge, (v) a unique serial number of the cartridge, (vi) a unique serial number of the dispensing device, (vii) stored temperature and humidity readings, (vii) unauthorized attempts to open the dispenser since the last dose was dispensed, (ix) the date and time of the last dose dispensed, (x) digital data generated by a wearable device, consumable, implanted, or ingested diagnostic device, monitoring device, machine, instrument, gadget, elaborate design, device, instrument, appliance, tool, institution, smartphone, digital camera, and information equipment (informalgizmos), etc., xi) from a separate dispenser or interface device (smartphone), Patient self-assessment data from an input screen on a tablet and/or computer, etc.), (xii) patient self-test information/data from an input screen on a standalone dispenser or interface device (smartphone, tablet and/or computer, etc.) and (xiii) self-report information from a query screen, digital log (e.g., Apple iPhone Health App) and/or from an input screen on a standalone dispenser or interface device (smartphone, tablet and/or computer, etc.).

The novel opioid-specific and patient-customized App integrates opioid-specific HIPPA and/or similar healthcare information protection regulations and guidelines, conforms to an opioid-specific dispensing algorithm, uses encrypted communications to control drug dispensing equipment and communicate with patients, centralized data servers, and integrated support centers and/or designated prescribers, physicians, caregivers, and/or family members. The algorithm uses prescription information, dispensing equipment information, kit information, the prescriber's DEA and/or unique identification number, digitally captured and/or patient entered self-assessment, and/or self-test, and/or self-reported physiological, psychological, lifestyle, concurrent medication and/or environmental data (digitized information and/or values) in a novel medication specific diagnostic algorithm to determine whether the medication dispenser should dispense an opioid or to keep the dispenser from dispensing an opioid by keeping the tamper-resistant dispensing unit locked.

Opioid specific dispensing algorithms utilize incorporated opioidsSpecial overscreening diagnosis OverDoseScreen for sample substance^TMTo determine whether an opioid dose should be dispensed or not, even if the opposite prescription permits. The opioid specific overdose diagnosis is specific for each opioid and each opioid preparation. The purpose of the opioid specific overdose diagnostic is to reduce opioid overdose.

The novel integrated system is designed to enable the use of a variety of medicament dispenser configurations, designs and sizes. They may be limited to a single medication or configured to dispense multiple medications. The medicament dispenser may be a disposable unit or a reusable unit. Regardless, the dose dispensed from each drug dispenser is controlled by an opioid-specific and patient-customized App. The App may reside on a standalone version of the medication dispenser or may reside on an interface device (e.g., smartphone, computer, tablet, etc.). Disposable medicament dispensers and reusable medicament dispensers are described below.

The disposable medication dispensing apparatus (disposable medication dispenser) is designed to: (i) suitable for a trouser pocket and/or purse, (ii) waterproof and dustproof, (iii) resistant to dropping and/or bumping, (iv) operating at and resistant to high and low temperatures within a defined temperature range, (v) powered by a battery having a lifetime equal to or longer than the opioid lifetime, (vi) an opioid-containing cartridge having a docking (dock) into a dispenser housing, (vii) a dispenser housing having tamper resistance, which is an integral unit, which is inaccessible to the opioid in the cartridge except for dispensing a single opioid dose, (viii) remains locked from dispensing unless the dispensing device receives a cryptographic signal authorizing the dose to be dispensed from the opioid-specific App, (ix) one-click dose dispensing. When the drug dispensing device completes a secure handshake with the opioid specific App, the drug dispenser delivers: (i) its serial number, (ii) the current and historical temperature and humidity levels since the last dispensing, (iii) any alert regarding an attempt to open the medication dispenser since the last dispensing of the opioid dose, (iv) any medication dispensing error message since the last dispensing of the medication, and (v) the date and time the last dispensing of the opioid dose. The medication dispensing apparatus may be configured to dispense one or more medications from a single cartridge.

Reusable medication dispensing apparatus (reusable medication dispenser) is designed to: (i) adapted to fit in a trouser pocket (for a single opioid unit) and/or a purse and/or belt sleeve (single or multiple drug dispensers), (ii) waterproof and dustproof, (iii) resistant to being dropped and/or bumped, (iv) operating at and resistant to high and low temperatures within a defined temperature range, (v) reusable, (vi) powered by replaceable and/or rechargeable batteries, (vii) having an opioid-containing cartridge that can only be docked or removed by an authorized medical professional, (viii) having a tamper-resistant dispenser housing that is an integral unit that is inaccessible to the opioid in the cartridge except for dispensing a single opioid dose, (ix) remains locked from dispensing unless the dispensing device receives an encrypted signal authorization to dispense a dose from an opioid-specific App, and (x) one-click dose dispensing. When the drug dispenser completes the handshake with the opioid specific App, the drug dispenser delivers: (i) its serial number, (ii) medication information on the cartridge, (iii) current and historical temperature and humidity levels since the last dispensing, (iv) any alert regarding an attempt to open the medication dispenser since the last dispensing of an opioid dose, (v) any medication dispensing error message since the last dispensing of medication, and (vi) the date and time of the last dispensing of an opioid dose. The medication dispensing apparatus may be configured to dispense one or more medications from a single cartridge or from more than one cartridge when a multiple medication dispensing apparatus is used.

The single medication dispensing device is controlled by a single App.

The multi-drug dispensing unit utilizes multiple cartridges (one for each drug) controlled by a consolidated App that combines individual drug apps into a single user interface to eliminate duplication of inputs and facilitate one-click drug dispensing for one or more drug treatments. The exchange of signals between apps is controlled by a biometric security system.

Single opioid-specific apps as well as multi-drug apps require a patient to perform a biometric login and make assignment decisions using drug-specific decision tree algorithms and drug-specific diagnostics and/or digitally captured and/or patient-entered self-assessment, and/or self-detection, and/or self-reported physiological, psychological, lifestyle, concurrent medication and/or environmental information (data/values). Encrypted biometric and/or alternate logins include, but are not limited to, iris scans, login names and passwords, fingerprint scans, unique hand motion sequences, voice controls, face scans, unique statements, unique codes sent to the patient's cell phone, etc.

Once the biometric log-in is completed and the information needed for dispensing the diagnosis is captured, clicking the medication dispenser control button can give the patient information to dispense the opioid and/or related medication if everything is within the normal range. No further communication with the patient is required.

However, if the algorithm determines that it is necessary to keep the dispensing device locked rather than dispensing, several alternative messages are displayed on the screen of the dispensing device and/or the interface device, even within the prescription guide. Such information includes telling the patient that the required opioid dose is not prescribed authorized for a specified period of time, and indicating that the dose should not be taken even within the prescribed dosing schedule parameters if not first communicated to an integrated support center or a prescribed healthcare professional. The App facilitates the invocation of the support center with a single-click alarm window. The integrated support center can distribute queries to physicians, payers-determined disease management support centers, or can act as a patient's medical support center and/or as disease management.

The App uses biometric login and encrypted communications with the servers and support centers of the data center to record and communicate to the appropriate parties (integrating the support centers, nursing staff, authorized family members, etc.) that, for example, (i) the patient may be about to take an undesired event, (ii) the prescription should be changed, (iii) the medication may have to be changed based on efficacy considerations, (iv) the patient has attempted to dispense an opioid dose too many times early (depending on the opioid), (iv) appears to be in a misuse or abuse mode, etc., (v) prescription guidelines are not followed, and (vi) no medication is taken, etc.

App is unique for each drug and/or each patient. The prescriber may select certain algorithmic interface screens to capture information according to a defined schedule or sequence, allowing better patient management and personalization of drug therapies. The medication dispensing algorithm may or may not make use of these screens to make dosage dispensing decisions. For example, the prescriber may instruct the App to present a pain self-assessment screen to track the effectiveness of opioids in controlling patient pain and monitor for increased opioid tolerance; stool consistency (self-reported) and/or bowel movement frequency (self-reported) to determine whether the patient is trending towards opioid induced constipation, and/or SpO2 (blood oxygen saturation self-test) to determine whether the opioid is causing a reduction in respiratory rate, etc., and/or pulse rate (digitally captured) as part of the dispensing procedure.

The prescriber may request a constipation self-report message to enable the algorithm to: 1) make an allocation decision and/or 2) warn the patient that he/she appears to be constipation and that the patient should consider taking a laxative, and/or 3) advise the patient to consult a support center to determine whether taking a laxative is advisable, and/or 4) notify the prescriber that the patient shows evidence of opioid induced constipation, etc. Another example is the prescriber specifying that the App requires conversational self-detection and/or cognitive self-detection and the completion of concurrent medication self-reporting, etc. as part of the assignment request process. The prescriber will use this specific information to prevent potential drug-drug interactions, etc. As determined by the prescriber, a corresponding screen may be presented each time prior to dispensing or based on a determined interval or as a result of a digital reading or other screen input, etc.

The prescriber may also specify that certain opioid-specific side-effect information be tracked through specific side-effect input screens, even if they are not required by the dispensing algorithm, to better manage the patient. If the prescriber chooses to track a side effect or side effects, the prescriber may specify the frequency at which each should be tracked, e.g., before each dose is dispensed, once per day, once per week, when the tracking value exceeds or falls below a specified range, etc.

Prescription information and prescriber-specified side-effect tracking information may be automatically digitally uploaded or manually entered into an opioid-specific and patient-customized App. This system typically requires the use of a new 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 synchronizes the data input interface with the electronic prescription program (e.g., ADSC MedicsRex, Allsccripts, DAW Systems, DrFirst Rcopia, MDT Toolbox-Rx, Medtab RxCy, OA Systems, Practice Fusion, RxNTeRx, Spectra eRx, etc.) and/or the pharmacy prescription system (e.g., OmniCare, QS/1, PharMerica, Frameworks, etc.) and/or the electronic prescription network (e.g., Surecrripts-which seamlessly connects the prescriber with the pharmacy), thereby eliminating duplicate entries. The prescription API enables the prescriber to specify his/her additional information capture and/or side effect tracking and their respective tracking frequencies and to enter patient authorized caregivers and healthcare professionals alert notification authorization and its associated contact information.

Elimination of duplicate entries may also be facilitated by integrating the data through the use of a network, such as a surescales electronic prescription network, which seamlessly connects the physician with the pharmacy. The network allows for the secure, reliable transfer and delivery of electronic prescription orders and update authorization requests between the computer of the pharmacy and the computer of the physician's office. Simultaneous transmission to a patient database residing on a central server may be accommodated.

After submitting an electronic prescription (which may also occur from a written prescription at the pharmacy), information from the prescription interface is sent to a patient database residing on a central server. Upon receipt, the opioid-specific and patient-customized App generation program creates a patient-specific database and generates a specific authorization code (e.g., patient identification record number, dispenser opening code for a reusable medication dispenser, etc.), links the prescription, patient, and pharmacy with the App, and then automatically generates a patient-and opioid-specific App, which is a copy that is retained on the central server. The program then automatically sends an email and/or text message to the patient via the App download link. Clicking on the link or copying the link to a navigation bar on an internet browser will bring the patient to the patient and opioid specific App download page. Clicking the "download button" automatically downloads the App to the interface device. Once patients download the opioid-specific and patient-customized App, they receive a separate email with a unique patient identification number. At this point, the patient is able to combine the drug dispenser with the opioid specific App. The update may also be achieved by wireless connection and by wireless connection or USB cable interface for a multi-drug reusable drug dispenser or the like.

For reusable medication dispensers, this is a procedure that is typically performed when a pharmacy inserts a USB cable to power a mechanical open and close locking mechanism on the medication dispenser and enters a dispenser opening code that is restricted by a healthcare professional (reusable opioid dispensers can only be loaded by authorized healthcare professionals).

The initial click App asks the patient to provide their patient identification number, some personal information, establish a biometric authentication baseline, and technical support password and challenge question information that was previously sent to them by email. Upon completion, the patient is able to access the medication dispensing algorithm using a biometric login. If they fail, they may request a reset password, or may contact a technical support integrated support center to provide a temporary password after the patient has correctly answered certain challenge questions. If desired, the integrated support center may enable patients to dispense opioid doses while they are coordinated with the patient to address their biometric entry issues. The integrated support center may be contacted by clicking a dial key on the alarm screen of the opioid-specific and patient-customized App or by dialing the number of the listed integrated support center.

The App allows the patient to ask certain questions about: when they have taken their last dose of opioid (or for a multi-drug dispenser, medication), how much medication remains, when their next dose expires, the expiration date/expiration date of the medication, package insert information for the medication, etc. It also provides access to personalized analysis charts, some of which may be downloaded from a server of the integrated support center or created by the App from limited information stored by the App to show how the patient's symptoms are affected when the patient takes opioids over time. This is intended to help the patient's prescription persistence, reinforce the importance of prescription compliance, and assist the patient in discussing with the prescriber regarding pain management and any opioid tolerance and/or side effect issues (depending on the type of information the prescriber is tracking).

The integrated support center's IT system (data server) stores authorized login information, all App history data and enables continuous updating/synchronization of App history on all patient devices where opioid-specific and patient-customized apps have been downloaded. The centralized server is also intended to: (i) updating personal App software as needed over the internet, (ii) updating patient electronic medical records residing on a central server, (iii) updating patient-specific advisor screens of an integrated support center in real-time, (iv) performing metadata analysis on the patient's personal data and analyzing de-identified (de-identified) patient data, which may include information from the patient electronic medical records, as well as from other patients with similar clinical manifestations, (v) performing comparative patient analysis on the metadata in patient populations with similar characteristics, and the like. The analysis output is intended to help integrate the support center and/or payor-specified disease management groups and/or the patient's caregivers to suggest individual patients and any reports and contacts with the prescriber, the patient and/or payor-specified disease management center and/or the patient's physician, etc.

The integrated support center IT system is designed to allow the integrated support center to lock and unlock the dispensing capabilities of individual medication dispensing units based on discussions with the patient's opioid-specific App, (i) based on an authorized prescriber instruction to change the patient's prescription, (ii) if tampering is suspected, locking the dispenser (and following established patient, prescription, and/or disease management protocols to determine the next step the integrated support center should follow), (iii) based on discussions with the patient and/or their caregiver, and (iv) locking all appropriate dispensing devices containing recalled opioids, and via a message on the patient's mobile phone, tablet and/or computer, patients are instructed to go to their pharmacy for the replacement opioid or follow the instructions of the manufacturer for the recall by short message, by email, talk message, by twitter, and/or any other similar communication service.

The support team of the integrated support center uses metadata analysis and opioid registration information as required by the prescribing medical professional to help them develop an optimal course of treatment based on specialized queries of the integrated support center's database and any authorized related electronic medical records. The integrated support center may also utilize the de-identified patient data to compare with individual patient information to determine potential medication issues (e.g., underdosing, overdosing, increased tolerability, addiction and/or dependency risk, potential abuse, etc.) to assist physicians in managing/better managing the patient's pain management needs/medications on an aggressive basis.

Brief description of the drawings

Advantages of embodiments of the present invention will become apparent from the following detailed description of exemplary embodiments of the invention, which description should be considered in conjunction with the accompanying drawings, in which:

FIG. 1 is an exemplary embodiment of a closed loop system for controlling opioid transfer, misuse, abuse, addiction, dependence, overdose, and death.

Fig. 2 is an exemplary embodiment of a closed loop opioid drug dispensing system controlled by an opioid-specific App containing a drug-specific dispensing algorithm.

FIG. 3 is an exemplary embodiment of prescription interface data capture between an electronic prescription prescriber and/or a pharmacy program.

FIG. 4 is an exemplary embodiment of the following logic: prescription information is entered in the pharmacy database and in the patient database, and a dispenser opening code (not required by the disposable medication dispenser) and patient identification number are generated and the dispensing App is authorized to dispense medication from a particular medication dispenser. Instead, prescribed opioid doses are rejected from more than one drug dispenser (where there are multiple opioid-containing drug dispensers). This logic prevents multiple dispensing/abuse by using multiple medication dispensers.

Fig. 5 is an exemplary embodiment showing a specific App module controlling an opioid specific App of a medication dispenser.

Fig. 6 is an exemplary embodiment of biometric authentication settings and login.

Fig. 7 is an exemplary embodiment of loading a cartridge into a reusable medication dispenser. The cartridge is preloaded and sealed into the disposable medication dispenser.

Fig. 8 is an exemplary embodiment of how firmware, databases, and software of a medication dispenser may be updated/synchronized.

Fig. 9 is an exemplary embodiment of data synchronization between a patient database and an opioid specific App.

FIG. 10 is an exemplary embodiment of an interface database organizational structure and relationship to a patient database.

Fig. 11 is an exemplary embodiment of the starting logic sequence when a patient accesses an opioid specific App and the App logic checks to ensure that the opioid is valid.

FIG. 12 is an exemplary embodiment of a prescription dispensing compliance sequence.

Fig. 13 is an exemplary embodiment of accessing and storing digitally captured patient data/values.

FIG. 14 is an exemplary embodiment of entering and storing patient self-assessment, self-test and/or self-report values.

Fig. 15 is an exemplary embodiment of information capture and storage of concurrent medication, tracked medication side effects, and additional clinical trial patient information.

Fig. 16 is an exemplary embodiment of a flow chart/decision tree for use with the opioid specific medication dispensing algorithm.

Figure 17 is an exemplary embodiment of a support taxonomy used by an integrated call center for responding to medication dispensers and/or medication dispensing problems.

FIG. 18 is an exemplary embodiment of a flow chart of a standard prescription entry, patient self-assessment, patient self-test, patient self-report, digitally captured value and/or information, and medication dispensing or dispensing control screen.

Fig. 19 is an exemplary embodiment of different devices and types of data that may be digitally captured by an opioid-specific App utilizing various Application Programming Interfaces (APIs).

Fig. 20 is an exemplary embodiment of a medication dispenser and associated cartridge docking device.

Fig. 21 is an exemplary embodiment of how the medicament dispenser may be lengthened or widened to accommodate larger pills and/or more medicament doses or widened to accommodate more than one cartridge.

Figure 22 is an exemplary embodiment of other medicament dispenser designs and different medicament dispenser configurations.

Fig. 23 is an exemplary embodiment of different drug cassettes and the number of different sized tablets that a single drug cassette may hold according to various exemplary pill configurations.

Fig. 24 is an exemplary embodiment of a patient value reporting screen of patient dosing time versus patient self-assessment, patient self-testing, patient self-reporting, and/or numerical reporting.

Fig. 25 is an exemplary embodiment of various multi-drug dispensers and combination therapy apps designed to hold more than one cartridge.

FIG. 26 is an exemplary embodiment of a centralized IT system for supporting various medication dispensing systems.

FIG. 27 is an exemplary embodiment of an integrated support center, classification center.

Fig. 28 is an exemplary embodiment of how the flip cover design of the reusable medication dispenser may be assembled to achieve secure, tamper-resistant closing and opening.

Fig. 29 is an exemplary embodiment of an electronic schematic of a medication dispenser.

Figure 30 is an exemplary embodiment of the placement of electronics and mechanical components external and internal to a medication dispenser.

Figure 31 is an exemplary embodiment of the correlation of opioid plasma levels and pupil size using oxycodone as an example.

Figure 32 is an exemplary embodiment of how pupil size may be used as an opioid overdose screening/diagnostic indicator.

Fig. 33 is an exemplary embodiment of the anatomy of the eye and the difference in dilation from light to dim light.

Fig. 34 is an exemplary embodiment showing how iris and pupil data may be detected, verified, and captured to guide allocation or non-allocation decisions.

Fig. 35 is an exemplary embodiment of an algorithm for making an allocation or non-allocation decision starting from captured normalized pupil data.

Fig. 36 is an exemplary embodiment of a data capture screen and sequence for motor skill self-detection for determining cognitive impairment.

FIG. 37 is an exemplary embodiment of the dispense or no dispense oxycodone algorithm for motor skill self-testing.

Fig. 38 is a continuation of the exemplary embodiment of the oxycodone dispensing or non-dispensing algorithm for motor skill self-testing shown in fig. 36.

Fig. 39 is an exemplary embodiment of an oxycodone dispensing patient interface using a combination of pupil scanning and motor skill self-detection to reduce the number of false positives (e.g., false dispense or no dispense decisions).

Fig. 40 is an exemplary embodiment of an opioid dispensing algorithm (using oxycodone as an example) used with pupil scanning and motor skill self-detection in a sequential order decision logic intended to reduce the number of false positives (e.g., false dispense or no-dispense decisions).

Fig. 41 is an exemplary embodiment of a sequential use self-assessment and self-reporting screen for reducing the number of erroneous opioid dispensing or non-dispensing decisions.

Fig. 42 is an exemplary embodiment of an algorithm that uses self-assessment and self-reporting responses to reduce the number of erroneous opioid dispensing or non-dispensing decisions.

Detailed Description

I. Terms and abbreviations

As used in this document, the term "i.e." means the terms used interchangeably:

misuse(i.e., substance abuse, substance therapy abuse, drug abuse, opioid abuse, etc.) means improper administrationBehavior or practice with drug therapy (e.g., opioids, anxiolytics, antidepressants, stimulants, etc.). It also refers to compulsive, excessive and self-injurious use of habituated drugs or use of harmful amounts of opioids, resulting in addiction or dependence, severe physiological damage (e.g., kidney, liver, heart damage) and/or psychological damage (e.g., dysfunctional behavioral patterns, hallucinations, memory loss) or death.

Addiction (addiction)(i.e., drug addiction, substance use disorders, opioid addiction) is defined as a chronic, recurrent disease characterized by the finding and use of compulsive drugs, regardless of deleterious consequences. For example, in the case of opioids, it refers to the compulsive need and use of one or more opioids (e.g., habituated substances) characterized by tolerance and clear physiological symptoms after withdrawal; in broad terms: the user is continuously forced to use substances known to be harmful.

Adverse events(i.e., AE, adverse event, adverse experience, adverse drug event, ADE, adverse drug response, ADR, or unexpected adverse drug response, etc.) refers to (i) a medical event that is related to the time of use of a drug product, but not necessarily causally related, (ii) any response to a drug that is harmful and unexpected and typically occurs at doses used in humans to prevent, diagnose, or treat a disease or alter physiological function, (iii) an unexpected response that is inconsistent with the characteristics of the drug or applicable product information, and (iv) unexpected effects that occur at normal doses that are related to the pharmacological properties of the drug, etc.

As used in this patentJoint medical care professionalRefers to all non-physician healthcare professionals who are engaged in caring for patients, including nursing, physician's assistants, medicine, and pharmacies, who may or may not have the right to prescribe opioids.

API(i.e., 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 being two applications or programsA shared interface that allows both to communicate with each other.

Expiration date(see due date).

Biometric authentication(i.e., biometric authentication, biometric enrollment) includes, but is not limited to, biometric technology for digitally capturing fingerprints, palm and full-hand scanners, talk and face recognition systems, iris scanning technology, pupil scanning, file readers, biometric software, and related services that can be used wirelessly, removably, or permanently to limit patient access. In this document, the term also includes any system that allows access by using a login name in combination with a password and/or any additional security information (e.g., a computer generated password sent by a server via email and/or text messaging), as well as programs developed to allow personalized actions or movements, etc., to restrict non-biological identification that is accessible only to the patient.

Explosive dose (i.e.: BTD, rescue dose)Is an additional dose of drug as needed to control breakthrough pain (transient exacerbation of pain occurring in the context of relatively well-controlled baseline pain, for treatment/management of sporadic pain exacerbations). It does not replace or delay the next conventional dose.

Nursing staffAny individual defined to assist a patient in identifying, preventing, managing and/or treating a disease or deficiency, such as a physician, nurse, disease management representative, joint health professional, social worker or family member, guardian or friend. .

CDC(i.e., centers for disease control and prevention).

Central server(i.e., cloud server, centralized server architecture) refers to a centralized computer system that stores all patient-related data and communications. It refers to the hardware where programs and databases are stored to support all patient specific activities needed to manage and control the relevant medication dispensing.

In this patentCognitive computingRefers to the calculation ofThe machine system, most notably IBM Watson, relies on deep learning algorithms and neural networks to process information by comparing it to a teaching data set. The more data the system is exposed to, the more learning, and the more accurate over time. Neural networks are complex "trees" of decisions that computers can make to arrive at an answer. The program helps to collate the range of knowledge surrounding a condition (e.g., a patient's pain), including patient history, journal articles, best practices, diagnostic tools, etc., analyze a large amount of information, and provide recommendations regarding the optimal course of treatment to manage pain. Cognitive calculations may also be utilized to continuously analyze the metadata to compare trends in the patient, such as pupil scans, to predict whether the patient is at risk for overdosing. Alternatively, cognitive calculations can be used to track pupil size, early dispensing attempts, drug dispenser tampering attempts, and pain self-assessment scores, as well as other patient data, to alert the prescriber of potential opioid dependence, addiction, abuse, and/or transfer problems. The integrated support center may utilize cognitive calculations to help guide the support center advisor whether the required opioid drug dispenser lock and dispensed dose should be unlocked using face recognition (via images from the patient's smartphone) and tonal analysis.

Compliance(i.e., compliance, capacity, prescription compliance, medication compliance) describes the extent to which a patient correctly follows the prescribed medication dose, dispense and store instructions.

Merging apps(i.e., multi-unit dispenser App) is an App designed to recognize other medication-specific apps present on separate dispensers or interface devices and then combine the necessary digital capture information, patient self-assessment screens and/or patient self-test screens and/or patient self-reporting screens into a single interface to control and dispense multiple medications.

Data input interface(i.e., data interface, data input) refers to a program designed to interface with an applicable electronic prescription program (e.g., ADSC MedicsRex)Allscripts, DAW Systems, DrFirst Rcopia, MDT Toolbox-Rx, Medtab RxCure, OA Systems, Practice Fusion, RxNT may Rx, Spectra ecrx, etc.) and/or pharmacy prescription Systems (e.g., OmniCare, QS/1, PharMerica, Frameworks, etc.) and/or electronic prescription networks (e.g., ureScripts, which seamlessly connects the prescriber with the pharmacy) to simplify patient data entry and minimize or eliminate duplicate data entry requirements.

Depend on(i.e., body-dependent) refers to the physiological adaptation of the body to the presence of substances, such as opioids. It is defined by the development of withdrawal symptoms when the substance is discontinued or when the dose is suddenly reduced, or in particular in the case of opioids, when an antagonist (e.g. naloxone) or agonist-antagonist (e.g. pentazocine) is administered. Physical dependence is a normal and prospective aspect of certain drug treatments and does not necessarily imply that the patient is addicted.

Digital captureRefers to digital patient data captured by a diagnostic or monitoring device and stored and/or transmitted in a machine-readable format. The digitally captured information may come from a variety of sources, such as apps present on a smartphone or computer, data captured by a medication dispenser, from an RFID chip embedded in the medication, from self-portrait images, from biometric logins (e.g., pupil size), from a digital interface, from a digital diagnostic device, and/or from a digital monitor, among others. The data may be used by the opioid dispensing algorithm to make dispensing decisions and/or by the prescriber to better manage the patient, and/or by the sponsor of the medication to capture clinical trial information, and/or by the patient to determine the effectiveness of opioid treatment and control of pain, etc.

Distribution point(i.e., pharmacy) is defined as a pharmacy or any other medical facility that dispenses prescriptions, a physician's office, a clinic, or a patient's home.

Dispensing systems (i.e., stand-alone dispensing systems, disposable dispensing systems)Opioid, kit containing opioid, and drugAn opioid dispenser, an opioid specific App containing an opioid specific dispensing algorithm, a stand-alone drug dispenser or interface device in which the opioid specific App is present, and an integrated support center and its associated databases and data servers. The independent dispensing system consists of an opioid, a kit containing the opioid, a drug dispenser, and an opioid-specific App containing an opioid-specific dispensing algorithm. The disposable dispensing system consists of an opioid, an opioid-containing cartridge (which may be an integral part of the drug dispenser, the drug dispenser), an opioid-specific App containing an opioid-specific dispensing algorithm, an interface device (which may also be a stand-alone drug dispenser) in which the opioid-specific App is present, and an integrated support center and its associated databases and data servers. All medication dispensers interact with and are associated with an integrated support center and its associated databases and data servers.

Transfer of(i.e., opioid transfer, drug transfer) is a medical and legal concept that involves the transfer of any legally prescribed controlled substances from the prescribed individual to another for any illicit use.

Butted togetherRefers to a cartridge present in a drug dispensing unit. Docked may also refer to a drug dispenser stored in a multi-drug dispenser dispensing unit.

Medicine(i.e., opioids, drugs, medications, medicaments, over-the-counter medications, supplements, herbs, etc.).

Medicine boxIs a reusable or disposable unit containing an opioid for dispensing during a prescribed period of time and/or days as prescribed, designed to be docked to a drug dispenser or designed as an integral part of a disposable drug dispenser. The cartridges may be pre-filled with the opioid from the pharmaceutical manufacturer or filled by a pharmacy or by a medical professional anywhere authorized to dispense the opioid. The cartridge may be a separate piece designed to be docked to the medication dispensing unitThe device may be a stand-alone device or may be an integrated cartridge in a disposable medication dispenser.

Medicament dispenser(i.e., dispensing apparatus, opioid dispenser, stand-alone dispenser, dispensing unit, disposable drug dispenser, disposable dispenser, etc.) refers to a drug dispensing unit with a docked or integrated cartridge whose dispensing is controlled by an opioid-specific App or stand-alone drug dispenser with a resident (residual) opioid-specific App or a drug dispensing program that controls the dispensing of doses of drug through the dispenser.

Medication dispensing unit(i.e., reusable drug dispenser, drug dispensing device, drug delivery device, stand-alone drug dispenser, disposable drug dispenser, multi-drug dispenser) is a device in which the cartridge is located in the dispensing unit and its dispensing mechanism (locking, unlocking and dispensing) is activated by firmware controlled by the opioid-specific App and/or drug-specific App or resident software logic contained in the stand-alone drug dispenser.

Drug dispensing softwareRefers to dispensing software residing on the interface device or on a stand-alone medication dispenser: which 1) requires biometric authentication and 2) controls the dose dispensing by the drug dispenser/drug dispensing unit.

Drug specific dispensing algorithmRefers to a decision tree-based algorithm developed specifically for each opioid and opioid preparation to determine whether a drug dose should be dispensed.

Electronic medical record(i.e., EMR, electronic health record, HER, patient case, PMR, etc.) refers to a systematic collection of health information stored electronically by patients and groups in digital format. These records may be shared among different healthcare facilities. The centralized electronic medical record for each patient maintained by the integrated support center on its centralized server is intended to store all captured opioid/drug dispensing information as well as all interactions between the integrated support center representation and medical personnel and patients and/or caregivers. The letterInformation is available to authorized providers to meet the HIPPA guidelines and general requirements for protecting and sharing health information. It captures and stores all information captured by the App as prescribed by the physician prescribing or clinical trial requirements, as needed.

Encryption(i.e., encrypted communications) is the most efficient way to achieve data security. Access requires a key or password that can be decrypted. Unencrypted data is called plain text; the encrypted data is called ciphertext. By definition, the encryption used in this patent is an encryption intended to meet all HIPPA security standards or general requirements for protecting health information.

Due date(i.e., expiration date, drug expiration date, expiration date/expiration date) refers to a date after which the drug should not be taken (should not be dispensed) because of the expected reduction in quality or effectiveness. For this patent, the expiration date is the shorter of the manufacturer specified expiration date and the pharmacy specified "expiration date". The "expiration date" is the date the pharmacy has placed the prescription, noting when the prescription should no longer be used. It often writes "throw away after.

FirmwareIs embedded system software contained in the memory of the medication dispenser to provide operating system control, sensor information capture, alarms, and signal exchange with the interface device.

Signal exchange (Handshake)(i.e., digital handshaking) refers to the exchange of signals between devices to ensure synchronization each time a connection is initially established with another device.

Integrated support center(i.e., call center, patient support center, physician support center, prescriber support center, etc.) refers to an integrated support center intended to: (i) patient support related to drug dispensers, opioid specific apps, alerts, locked dispenser screens, opioids, or health related issues is provided. It can distribute calls from dispensers and App technical support to appropriate opioid advisors, prescribersA physician of the patient and/or any contractual disease management service; and/or (ii) assist the prescriber in optimizing the patient's opioid therapy, and (iii) answer any commercial questions (e.g., customer queries regarding invoices, bills, orders, pricing, shipments, etc.).

Interface deviceRefers to a smartphone, tablet, computer, or standalone medication dispenser, etc. with internet communications capability or similar communications capability in which an opioid-specific App is present, which allows communication with an integrated support central server (central computer).

Locked upIndicating that the dispensing device is unable to dispense the medicament until the opioid-specific App or the dispensing software of the stand-alone device unlocks the dispensing unit and allows it to dispense the medicament.

Long-acting medicine(i.e., sustained release, SR, controlled release, CR, extended release, ER) is a drug that is slowly effective after an initial dose, but retains its effect over a long period of time, is slowly absorbed and persists in the tissue before being excreted. They may exist in various forms, but are referred to in this patent as oral formulations or transdermal formulations by reference.

Long acting opioids(i.e., sustained release, SR, controlled release, CR or extended release, ER). They may be oral or transdermal.

Medicine(i.e. drugs, medicaments) means substances for medical treatment, in particular medicines or legal or illegal drugs, over-the-counter drugs, vitamins, dietary supplements, herbs and/or recreational drugs, etc.

As used hereinMetadata analysis(i.e., structural metadata analysis, descriptive metadata analysis, big data analysis) refers to an organization that uses patient data so that individual and patient population data can be analyzed to determine how to best manage opioid therapy on an opioid by opioid and patient by patient basis. For reference, it incorporates the use of cognitive computing to determineWhich optimally treats the pain of an individual patient based on the patient's own information as well as the patient's record of the de-identification, the patient's facial scan, and/or the patient's tone.

Opioids(i.e., opiates, short-acting opioids, long-acting opioids) refer to all agonists and antagonists with morphine-like activity, as well as naturally occurring and synthetic opioid peptides. This definition also includes all drug combinations that include at least one opioid in the drug combination. Examples of opioids are: buprenorphine, codeine, fentanyl, hydrocodone, hydromorphone, methadone, morphine, oxymorphone, oxycodone, tapentadol, tramadol and the like.

Special App for opioids(i.e., opioid-specific App, patient-customized opioid-specific App, opioid-specific and patient-customized APP, drug-specific App, App) refers to an application that requires biometric authentication before a patient can respond to a patient self-assessment screen and/or a patient self-detection screen and/or a patient self-reporting screen, which is used by the App's drug-specific dispensing algorithm to decide whether to signal the dispensing device to dispense an opioid or to indicate to the patient and/or an integrated support center why an opioid is not being dispensed.

Opioid quantitationTraditionally known as modulating the dose of opioid. It requires a regular assessment of the patient's pain, the time and cause of occurrence, and the amount of drug used over the preceding 24 to 72 hour period.

Opioid rotationIs the conversion of one opioid into another. It is desirable for patients with inadequate pain relief and/or intolerable opioid-related toxicity or adverse effects.

When the opioid is abruptly discontinued, it occursOpioid withdrawal. Withdrawal symptoms last for several days, usually in contrast to the symptoms exhibited at the onset of opioids.

Initial treatment with opioidsPatients refer to individuals who have never taken an opioid or who have not received repeated opioids for 2 to 3 weeks.

Opioid toleranceIs a state of adaptation in which exposure to the opioid causes a change resulting in a decrease in one or more effects of the drug over time. It is a known pharmacological effect of opioids. Tolerance to the analgesic effects of opioids is relatively uncommon.

Oral patient-controlled analgesia(i.e., OPCA) is any method that allows a person suffering from pain to administer pain relief to himself. Historically, this has been limited to infusion using infusion pumps that can be programmed by the prescriber. If the machine is programmed and operated as intended, it is unlikely that an excess of drug will be delivered. Embodiments of the invention extend the application to oral pharmaceuticals. The prescriber indicates a limit on the patient's oral opioid distribution. The allocation can be controlled as: 1) a prescribed number of pills (doses) within a determined time interval; or 2) the number of pills that can be prescribed within a defined time interval, the limitation being that the individual cannot dispense doses more frequently than a given schedule between doses (e.g., at least 20 minutes between doses), etc.

Patient's healthRefers to an individual who is prescribed and is taking opioids and/or drugs.

Patient databaseRefers to all patient data stored in the central server. The data may be stored in one or more databases and on one or more servers, collectively referred to as a patient database.

Results reported by the patient(i.e.: PRO) is a method or questionnaire used in clinical trials in which responses are collected directly from patients. The collection may be by automatic digital capture, or by patient-entered self-assessment, self-test, or self-reporting of physiology, psychology, and birthLive mode, drugs taken simultaneously, or environmental information/data.

Patient self-assessment(i.e.: patient reported outcomes, PRO) cover all potential types of measurements derived from: i) patient response to questions, (ii) self-administered testing, (iii) digitally captured self-reported input, and/or (iv) digital logs, the information of which may be quantified for utilization by drug-specific dispensing algorithms and/or by prescribers for better patient management and/or for clinical trial information reporting by drug sponsors. Each self-rating scale or question or log entry measures a single base characteristic. Examples include, but are not limited to, responses/reports, (i) pain levels (e.g., responses to the Mosby pain index, Wong-Baker face ghost scale, etc.), (ii) activity tolerance scale, (iii) quality of life scale, (iv) discomfort scale, (v) physiological values (e.g., blood pressure, heart rate, eye dilation, balance, gait, weight, food consumption), (vi) stress, (vii) oxygen saturation, SpO2, etc. This definition may include, but is not limited to, the detection of certain patient self-administration (also known as patient self-detection) or the observation of self-reporting (also known as patient self-reporting).

Patient self-testRefers to any test that is responded to by the patient and digitally captured to allow the medication dispensing algorithm to make a medication dispensing decision. Examples of opioid-specific suitability include, but are not limited to: (i) fine typing detection to determine cognition (speed and accuracy of movement); (ii) walking detection to determine balance and/or gait; (iii) speech detection to determine speech intelligibility and fluency; (iv) memory detection to assess cognitive state, motor function, attention/work memory, processing speed and executive function, and learning and memory, (v) manual acuity detection to determine alertness and cognition, (vi) data entry detection to determine cognition, and the like. This information may be quantified for utilization by drug-specific dispensing algorithms and/or by prescribers for better patient management and/or by drug sponsors for drug clinical trial data capture.

Patient self-reportingIs defined byAny response made by the patient based on his/her actions, observations, or best recall. Examples include, but are not limited to, (i) over-the-counter medications, herbs, or other medications taken within a predetermined period of time (e.g., in the case of opioids, this may be a problem related to the medication taken since the last opioid dose that would result in interaction with the opioid medication), (ii) how the patient 'S stool composition looks (e.g., on the bristoel stoolidex), (iii) the time of last bowel movement by the patient, (iv) digital logs (e.g., iPhone Health App, Samsung' S Health, disease-specific logs), and so forth. This information may be quantified for use by drug-specific dispensing algorithms and/or by prescribers for better patient management, and/or by drug sponsors for clinical trial data reporting, etc.

Patient-specific opioid-specific App (i.e., opioid-specific App)Refers to an opioid specific App used to control the opioid dose dispensed from a drug dispenser. The physician will automatically prescribe the relevant opioid when prescribed. The prescriber can customize the App for an individual patient by requesting that certain side effect information be tracked (which is not necessary for the drug-specific dispensing algorithm to make the dispensing decision). The opioid-specific patient-customized App may also be programmed to capture patient management and clinical trial information/data that is not necessary to make opioid dispensing decisions.

Persistence of action(i.e., prescription duration, drug duration) refers to the act of continuing treatment for a prescribed duration of time. It can be defined as the "duration from the start to the stop of the treatment". There is no general term to combine these two different constructs.

PharmacodynamicsIs the study of the biochemical and physiological effects of drugs on the body or microorganisms or parasites in or on the body and the relationship between the mechanism of action of drugs and drug concentration and effect.

PharmacokineticsIs the body absorption, distribution, metabolism andstudy of excretion.

Doctor's officeIs broadly defined as a medical facility, one or more rooms, in which physicians and staff provide patient care; one or more physicians receive and treat a patient's site therein. Examples include individual practitioner offices, physician combination offices, hospital clinics, outpatient ambulatory care centers, remote medical locations, and the like.

Compound medicineIs the practice of administering or using (particularly simultaneously) multiple drugs (as in the treatment of a single disease or several co-existing conditions).

Those who prescribe a prescriptionIs defined as any healthcare professional authorized by a respective country or state to write a prescription for a medication. Examples include physicians, physician assistants, nurse practitioners, nurses, pharmacists, and the like.

Prescription(i.e., electronic prescription, paper prescription, manually entered prescription, digital prescription, medication prescription) is an indication that a medication or treatment is to be provided to a patient by a medical practitioner with permission to enter electronically or manually.

Date of prescription dueIs defined as the drug due date or the earlier of the due date.

Recall from scratchRefers to an opioid recall issued by the manufacturer or regulatory agency indicating that a particular opioid lot or drug should not be taken.

Routine program(i.e., software programs, software routines, subroutines, programs, functions, methods, subroutines) are portions of software code within a larger program that perform particular tasks and are relatively independent of the remaining code.

Serial number(i.e., serial No., SN, S/N, identification number, tracking number, identifier, etc.) is a unique number used for identification, tracking, and/or inventory purposes.

Short-acting medicine(i.e., immediate release, IR) are fast acting opioids that require periodic repeated dosing for long-term treatment. They are rapidly absorbed, distributed in the body and discharged from the body.

Short acting opioidsIs an Immediate Release (IR) opioid.

Steady stateIt means that the availability and elimination of opioids (drugs) are equal to each other.

Tamper-proof(Tamper) refers to a design: 1) preventing the medication dispenser from opening without being tampered with, 2) making it difficult to replace, open, or remove the opioid cartridge in the medication dispenser other than by an authorized user, or 3) causing damage to the medication dispenser when an unauthorized person attempts to open the medication dispenser.

Tethered medicament dispenserAre medicament dispensers that take advantage of the capabilities of the interface device to provide functionality and ease of use that would otherwise not be possible in stand-alone medicament dispensers of the same size having the same external dimensions.

Quantification ofTraditionally, it is referred to as adjusting the dose until the desired result is achieved. Examples include opioids, dopamine and nitroglycerin. Quantification requires periodic assessment of the patient's symptoms/values over a defined period of time.

Quantitative box(i.e., metered dose dispenser, opioid dosing unit) refers to a kit that is configured with one or more opioids over a specified period of time to determine the correct dosage and schedule of administration of a single opioid or combination of opioids.

Tolerance to stressIs a pharmacological concept where the subject's response to a particular opioid and opioid concentration decreases after repeated use, requiring increased concentrations to achieve the desired effect. It is a state of adaptation in which exposure to opioids causes changes, resulting in a decrease in the effect of the opioid over time.

Total Daily Dose (TDD)Is the 24 hour total amount of opioid taken in both the regular and burst doses.

Giving upIs a group of symptoms that occur when the opioid is suddenly interrupted or intake is reduced. In order to experience symptoms of withdrawal, the patient must first develop physical or mental dependence. Withdrawal symptoms usually persist for several days.

List of opioids, opioid mechanisms of action and degree of pain suitable for use in various embodiments of the invention

The present invention and its various embodiments may enable the prescriber to better manage and personalize the patient's opioid drug therapy. The present invention may assist prescribers in personalizing patient opioid therapy including: (i) establishing a minimum effective opioid dose, (ii) continuously, real-time monitoring the ability of one or more opioids to manage the patient's pain, symptoms, and/or conditions, (iii) adjusting the prescribed dose if the patient develops sufficient opioid tolerance to require an increase in dose; (iv) facilitating opioid management to better control drug withdrawal, (v) reducing or preventing opioid overdose, (vi) preventing opioid abuse or misuse by limiting dispensing to prescribed dosing intervals, (vii) determining whether a patient is overdosed or underdosed by using patient self-testing, thereby improving opioid drug safety, (viii) reducing opioid-mediated side effects by utilizing patient self-assessment, (ix) avoiding unnecessary opioid medical professional intervention/office visits, associated emergency room visits, and/or death by preventing drug-drug adverse events, and (x) ensure proper prescription and prescription compliance by real-time patient data capture, controlling patient access to opioids, and prescriber feedback. By improving the safety profile of each opioid, the present invention improves the quality of care of the patient, ensures sustained efficacy of the opioid to each patient, improves the quality of life of the patient by ensuring proper prescription, and improves prescription compliance and persistence-thereby reducing the number of opioid-related medical interventions, physician visits, emergency room visits, and hospitalizations-thereby reducing the overall cost of patient care-thereby reducing the number of opioid overdoses of death. Opioid transfer leads to prescribed opioid addiction, overdose, misuse and abuse and associated medical costs, and the present invention also reduces medical costs by reducing opioid transfer.

Table 1, starting from the next page, lists the oral opioids. The approved drugs listed are included by reference in embodiments of the invention and may benefit from improved opioid safety profiles. The present invention alleviates the prescription risk for pharmaceutical manufacturers and prescribers because it transfers responsibility for prescription compliance to patients. By definition, the list of each drug includes the individual indications, intensity, dosage form, route of administration, side-effect profile, drug interactions, mechanism of action, manufacturer, etc. of each opioid.

In addition to table 1, embodiments of the present invention are incorporated by reference into all of the commercially available and developing oral opioids listed in the following documents: (i) goodman&Gilman's, The pharmaceutical basic of therapeutics (12 th edition) (Goodman et al eds.) (McGraw-Hill) (2011); (ii)2015Physician' sDesk Reference; (iii) cortex of Thomson road penetration^TMCompetition information; (iv) adis R&D; and/or (v) Pharmaprojects by Citeline. By definition, the list of each drug includes the individual indications, intensity, dosage form, route of administration, side-effect profile, drug interactions, mechanism of action, manufacturer, etc. of each opioid.

Table 1: approved opioids

TABLE 1 continuation

The side effects of each opioid are listed in the package insert for the opioid. Each side effect may be tracked using a corresponding patient self-assessment, patient self-test, and/or patient self-report screen or digitally captured diagnostic, monitoring, or patient maintenance information. Table 2 is an exemplary list of side effects that the prescriber may track using a prescription or selection on other input media that enables the data capture screen to be incorporated into the opioid specific App. The information may or may not be incorporated into the patient-specific assignment algorithm. The opioid-specific App may be customized to request information each time or at specified time intervals. This allows the patient opioid specific App to be customized for each patient to aid in patient management. The drug specific side effects for each opioid are listed in the package insert for each opioid and incorporated herein by reference.

TABLE 2 side effects of sample opioids

Opioids in the development process may utilize the present invention to capture the required clinical trial information and control opioid distribution for regulatory drug approval and control opioid distribution after regulatory approval. All opioids under development are included by reference in the embodiments of the present invention. FDA and similar regulatory agencies in general and opioid-specific approval self-assessment, self-test, self-report, digitally captured diagnostic test, digital log information, dispensing information, and other drug approval recommendation data acquisition and reporting guidelines are incorporated by reference. By definition, the listing of each opioid includes the individual indications, intensity, dosage form, route of administration, side-effect characteristics, drug interactions, regulatory approval guidelines, and the like, for each opioid.

The mechanism of action of commercially available oral opioid drugs, oral opioid drugs under development, and effective oral opioid drugs withdrawn from the market due to dose-related side effects or oral opioids whose development has been halted due to side effects that can be addressed by embodiments of the present invention, can be incorporated by reference. The drugs listed in the following databases are included by reference in embodiments of the present invention: cortex of Thomson road penetration^TMCompetition information; adis R&D; and Pharmaprojects by citline. The listing of each drug includes, by definition, each drug's individual indications, strength, dosage form, route of administration, side-effect characteristics, drug interactions, mechanism of action, and the like.

Oral opioids listed in the following databases (i) under development but interrupted by dose-related side effects, the safety issues of which could be solved by the present invention, or (ii) due to the dose phaseThe relevant side effects are withdrawn from the market after approval, their safety issues can be addressed by the present invention, and are contained in the following databases: (i) cortex of Thomson road penetration^TMCompetition intelligence, and/or (ii) AdisR&D, and/or (iii) Citeline's Pharmaprojects are included by reference in embodiments of the invention. The listing of each drug includes the individual indications, strengths, dosage forms, routes of administration, side-effect characteristics, drug interactions, mechanisms of action, regulatory approval guidelines, and the like, of each drug.

Systems and methods for controlling oral opioid delivery

Various embodiments will be described hereinafter with reference to the accompanying drawings. The embodiments are illustrated and described by way of example only and not by way of limitation. Alternative embodiments may be devised without departing from the spirit or 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. Furthermore, to facilitate understanding of the description, several terms used herein are discussed below.

The word "exemplary" is used herein to mean "serving as an example, instance, or illustration. Any embodiment described herein as "exemplary" or "exemplary" 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.

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 sequence 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. Additionally, 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.

Fig. 1 shows an exemplary embodiment of the present invention of a closed loop system for controlling opioid transfer, misuse, abuse, repeat dosing, addiction, dependence, overdose, and death.

The following is an exemplary description of the embodiment of fig. 1 of the present invention and how the different components relate to each other and how they together contribute to a closed loop opioid traceability control system:

by passingThose who prescribe a prescription2 identifies it with the following information: (i) a country provider identification (NPI) number, (ii) a DEA registration number, (iii) a state doctor license number, and/or (iv) other association and/or government identification numbers. This number is associated with the patient 6 on the prescription 4 and the prescription dispensing pharmacy 8.

Prescription4 are specific to the patient 6 and are associated with the prescriber 2, the pharmacy 8, the prescription database file for the patient 6 on the data server 10, and the opioid specific App 12. Prescription 4 information is loaded electronically or manually and is associated with a data server 10 and an opioid specific App 12.

Patient's health6 are related to: the prescriber 2, the prescription 4, the pharmacy 8, the data server 10, the opioid specific App12, the interface device 14, the drug dispenser 16, the individual cartridges 18 (which may be an integral component of the drug dispenser 16 in some embodiments of the invention), and any RFID 20 enabled device incorporated with the oral dosage form to indicate when the drug was ingested, any program that allows the patient 6 to take a self-photograph 21 of the self-administered opioid that automatically identifies the opioid.

When the prescriber 2 inputs the electronsWhen the prescription 4 is received by the prescription and/or pharmacy 8,pharmacy8 with patient 6 and prescriber 2; when the prescription 4 is first submitted by the prescriber 2 and/or filled by the pharmacy 8,pharmacy8 to a data server 10; when the App generation program 200 subsequently creates the opioid specific App12, which is then downloaded to the interface device 14,pharmacy8 was associated with opioid specific App 12.

When the prescriber 2 submits an electronic prescription 4 or when the pharmacy 8 fills out the prescription 4 and enters the prescription 4 instructions specific to the patient 6 of the prescriber 2,data server10 is associated with the patient 6. Upon receipt of the patient 6 and prescription 4 information, the App generation program 200 on the data server 10 creates an opioid-specific and patient-customized App12 containing a personalized, patient 6-customized drug-specific dispensing algorithm 13. In addition to the patient 6, prescriber 2, prescription number, pharmacy 8, medication, intensity, and medication schedule information, the prescription 4 may contain dedicated patient 6 self-assessment, self-testing, self-reporting, or digitally captured patient 6 information/data, which may be incorporated into the medication-specific dispensing algorithm 13 or may be captured to assist the prescriber 2 or other healthcare professional in managing the patient 6 or capturing information needed for medication administration submissions during clinical trials. The data capture may include patient information requested by the prescriber 2 that is not used by the medication-specific dispensing algorithm 13 to make dispensing or non-dispensing decisions, i.e., decisions to keep the medication dispenser 16 locked or unlocked and allow the opioid dose to be dispensed.

An API with a corresponding program that closes the closed loop opioid traceability control can be used to capture the dispensing information and/or self-taken picture 21 of the RFID pill 20, or the data server 10 can aggregate data from the electronic medical record 24 of the patient 6. This would then provide traceability of each opioid pill intact from the time the opioid was loaded into the cartridge 18 until the patient 6 consumed the opioid. If the data server is authorized to access the electronic case for patient 6 to comply with HIPPA and other government guidelines, the API may be utilized to access consumption data in the electronic case 24, update the database for patient 6 on the data server 10, and then update the information on the relevant opioid-specific App 12. This would provide true opioid traceability and accountability.

Opioid-specific and patient-customized App12 are generated by the data server 10 and are specifically configured/personalized based on prescription dispensing instructions and the side effects or values that the prescriber 2 wishes to monitor. This information may or may not be considered in the drug-specific dispensing algorithm 13 of the patient 6. Once the opioid specific App12 is generated, the dedicated patient 6 is given an identification number 160, which associates the opioid specific App12 with the patient 6. When the opioid-specific App12 is ready, the data server 10 sends an email and/or text message (and/or other similar communication) containing the patient's 6 opioid-specific App12 download link to download the App to his/her interface device 14 and/or stand-alone medication dispenser 16. At the same time, the data server 10 adds the patient 6 to the corresponding data server 10 patient database 152 file to facilitate receipt of the aggregated opioid specific App12 and the drug dispenser 16 serial number, cassette 18 serial number, drug NDC number, lot number, prescription 4 expiration date/expiration date, drug storage requirements and associated drug dispenser identification number 158 and drug specific events, alerts and information uploaded by the opioid specific App12 that are communicated thereafter. At the same time, the data server 10 determines available electronic case 24 links and creates relationships between all patient 6 related information/data files on the data server 10 to facilitate data gathering, analysis, querying, reporting, and the like.

Interface device14 is where the opioid specific App12 is present to tether the drug dispenser 16. The opioid-specific App12 connects to the interface device 14 through the phone number and/or IP address of the interface device 14. The opioid-specific App12 utilizes the memory, processor, speaker, camera, biometric authentication, communications connectivity (bluetooth, Wi-Fi, internet, etc.), telephone, and other features of the interface device 14 to enable the opioid-specific App12 to control the medication dispenser 16 and communicate with the patient 6, data server 10, integrated call center 22, prescriber 2, etc,Other healthcare professionals and paramedics, the pharmacy 6 (e.g., for replenishment, etc.), etc. (e.g., by screen message, vibration prompt, alarm, by sending email, text message, or making phone call, etc.).

Medicament dispenser16 are associated with the opioid specific App12 by exchanging the identification number 158 of the medication dispenser and/or a unique serial number that is exchanged with the opioid specific App12 during the first wireless connection/handshake. Thereafter, the opioid specific App12 uses the serial number of the drug dispenser 16 to ensure that it is connected to the drug dispenser 16 of the patient 6 containing the desired opioid. Once validated, the opioid-specific App12 controls opioid dispensing through the function and communication of the drug dispenser 16 as well as all other drug dispensers 16.

Medicine box18 has a unique cassette serial number and a unique lot number associated with the opioid NDC number and opioid specific information. The drug cassette 18 is docked to the drug dispenser 16 or is an integral part of the drug dispenser 16, with the drug dispenser 16 and the drug cassette 18 using the same serial number of the drug dispenser 16, depending on the design of the drug dispenser 16 (the drug cassettes 18 retain their own serial number in the reusable multi-drug dispenser 16). Upon docking, the cartridges 18 associated with the particular opioid and opioid lot number are associated with the medication dispenser 16, which in turn, the medication dispenser 16 is associated with the opioid specific App12, the data server 10, the pharmacy 8, the prescription 4, the prescriber 2, and the patient 6. Information about the opioids contained in the kit 18 is utilized by the drug-specific dispensing algorithm 13 of the opioid-specific App 12. The kit is in turn associated with a medication dispenser 16, the medication dispenser 16 is associated with an opioid specific App12, and the opioid specific App12 is associated with the patient 6, thereby providing a closed traceability control loop. It is desirable to have an opioid traceability control loop that shows patient 6 ingesting a particular dosage form.

RFID pill20 is an oral dosage form comprising a chip that transmits a signal when ingested. Can be used forTo configure the opioid-specific App12 with an API to acquire signals and capture ingestion information. The time interval between dispensing an oral dosage form and taking an oral dosage form indicates whether the dose is taken by the patient 6 or is likely to be transferred. The RFID chip is associated with an RFID pill 20, which RFID pill 20 is in turn associated with a medicine cassette 18. The kit is in turn associated with a medication dispenser 16, the medication dispenser 16 is associated with an opioid specific App12, and the opioid specific App12 is associated with the patient 6, thereby providing a closed traceability control loop.

The self-photographing 21 recognition software is designed to recognize the patient 6 and the solid dose of the pharmaceutical opioid that the patient 6 is taking. The patient 6 is associated with a medication dispenser 16 and an associated medication cassette 18 and an associated opioid. The time interval between dispensing of the opioid by the drug dispenser 16 and the captured administration of the opioid by the patient 6 is indicative of prescription compliance or opioid emanation by the patient 6. If the opioid is an RFID pill 20, it is a complete confirmation that the patient 6 did take the dispensed opioid-thereby closing the traceability control loop of this opioid pill.

Electronic medical record24 are created by the data server 10 at the same time that the first opioid-specific App12 is created for the patient 6. The electronic case 24 is configured to be discoverable by authorized caregivers using a National Record Locator Service (NRLS) such as surescans. The electronic case 24 is configured to distribute information and present any data captured by the opioid specific App12 and any medically relevant communications between the integrated support center 22 and the patient 6 from the interaction records. The data is automatically updated by the data server 10. The electronic medical record 24 may also be used to check to determine if any other prescribed medication may conflict with any new or existing opioid prescription 6.

Fig. 2 shows an exemplary embodiment of the invention: an integrated medication dispensing and patient management system, the system comprising: an opioid-specific App12 containing a drug-specific dispensing algorithm 13 residing on an interface device (smartphone, computer tablet, portable or desktop computer, standalone drug dispenser, etc. with bluetooth, Wi-Fi, and/or internet communication capabilities) 14 for controlling dispensing by a (single-drug or multi-drug) drug dispenser 16; an integration support center 22; a patient 6; prescription 2; and an electronic medical record 24 of the patient.

FIG. 3 is a block diagram depicting an exemplary embodiment of the prescription interface module 30, the prescription interface module 30 being designed to integrate data input with commonly used electronic prescription programs (e.g., ADSCMedicsRx, Allsacripts, DAW Systems, DrFirst Rcopia, MDT Toolbox-Rx, Medtab RxCy, OA Systems, Practice Fusion, RxNTeRx, Spectra eRx, etc.) and/or pharmacy prescription Systems (e.g., OmniCare, QS/1, PharMerica, Frameworks, etc.) and/or National Record Location Services (NRLS) such as the NRLS provided by SureSripts via an Application Program Interface (API). The requested information may be entered directly by the prescriber 2 and submitted to the pharmacy 8 and its pharmacy database 164 as well as the patient database 152 of the integrated support center 22. Any data not entered by the prescriber 2 may be entered at the pharmacy 8. These updates are automatically uploaded to the patient database 152. The patient 6 may enter any data not entered by the prescriber 2 and pharmacy 8. However, the information that patient 6 can input onto the opioid specific App12 prescription information screen using direct data entry is limited to only notification information 116-146. The data entered by the patient 6 is automatically uploaded by the opioid specific App12 and synchronized with the patient database 152.

The prescription interface 30 captures the patient's full name 32, the patient's street address 34, the patient's date of birth 36, the patient's gender 38, the PBM/payer unique member identification number 40, the cardholder's ID name 42, the group ID 44, the diagnostic code (ICD-10, ICD-11, etc.) 46, the prescriber's full name 48, the prescriber's full address 50, the prescriber's telephone number 52, the prescriber's fax number 54, the supervisor's identification number 56, the prescriber's agent identification 58, the prescriber's national ID (NPI)60, the prescriber's DEA number 62, the prescriber's electronic prescription network or supplier ID 64, the prescription date 66, the drug name 68, the drug NDC (national drug code number) 70, the drug strength 72, the dosage form 74, the prescription quantity 76, the usage instructions 78, the dosage frequency 80, the minimum time between doses 82, maximum daily dose 84, maximum number of days to administer 86, authorized supplements 88, product replacement code 90, Notes Field (Notes Field)92, previous authorization code 94, store (pharmacy) name 96, (store) street address 98, (store) phone number 100, NCPDP (national drug prescription committee) ID 102, prescription expiration date (expiration date, which is the drug expiration date or the earlier of 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-assessed, self-tested, and/or self-reported patient information that prescriber 2 wants to track to better manage patient 6 and/or obtain regulatory submissions needed for clinical trials) 108, side effects to track (this represents specific opioid-mediated side effects that prescriber 2 wants to track, digitally captured patient values and/or self-assessed, self-tested, and/or self-reported patient 6 information to better manage the patient 6)110, the prescriber's electronic signature or digital signature 112.

If the data loss 114 is a program routine for ensuring that all necessary recipe 4 data is captured, then completion is checked and requested. When the patient 6 dispenses or ingests (in the case of an RFID pill 20 or selfie 21 ingestion confirmation) the opioid, the standalone medication dispenser 16 or the opioid specific App12 informs the caregiver and/or family members with a notification message, providing a special notification if some intervention or action may be required. The type of notification sent to each person may be specified in the prescription interface or when the patient 6 enters the information directly into the opioid specific App12 or the stand-alone drug dispenser 16. The following are examples of data capture fields for notification information: reminder selection and scheduling 116, name of the prescriber 118, email of the prescriber 120, messaging telephone number of the prescriber 122, name of the disease administrator 124, email of the disease administrator 126, messaging telephone number of the disease administrator 128, name of the family 1 130, email of the family 1 132, messaging telephone number of the family 1 134, name of the family 2, email of the family 2, messaging telephone number of the family 2 140, name of the family 3, email of the family 3 144, and messaging telephone number of the family 3 146.

FIG. 4 is an exemplary embodiment of the following logic: (i) entering prescription 4 information into the pharmacy database 164 and (ii) into the patient database 152 and (iii) to generate the dispenser identification number 158 and (iv) patient identification number 160 required to create the opioid specific App12 and subsequently dispense the medication dose, which is required to create the opioid specific App12 and subsequently dispense the medication dose. The dispenser identification number 158 is a unique identifier for linking the prescription 4 to one or more prescribed medication dispenser 16 serial numbers. Once the dispenser identification number 158 is present, the logic proceeds to generate and transmit the patient 6 and opioid specific App12 to the patient 6 for download into their interface device 14. After the patient 6 activates the opioid specific App12, once App12 is bound to one or more drug dispensers 16, the opioid specific App12 is ready to control opioid dose dispensing.

The restricted dispenser identification number 158 is issued in response to the type of medication being prescribed. If the medication is, for example, a medication that has a dispensing problem, such as an opioid, the data server 10 issues a restricted dispenser identification number 158 when the prescription is submitted 150. The restricted dispenser identification number 158 limits the opening of the reusable drug dispenser 16 and docking of the opioid containing cartridge 18 to authorized medical professionals.

When the prescriber 2 or pharmacist (pharmacy) 8 submits 150 the electronic prescription 4, it causes the pharmacy database 164 and the patient database 152 to be automatically updated/synchronized. It is then checked whether there is already a dispenser identification number 158 required for the prescription opioid for patient 6 or whether a dispenser identification number 158 needs to be generated for the prescription opioid 154. If the answer is no 156, the program issues a restricted dispenser identification number 158 and automatically sends it to the pharmacy database 164 and the patient database 152 for inclusion in the prescription 4. The patient identification number 160 is then checked, which is used as a control number and identifier for all patient 6 data stored on the data server 10 and patient database 152. If not, the program generates a patient identifier 160. The program automatically sends the patient identification number 160 to the patient 6 via email and/or text message for use by the patient 6 when the opioid specific App12 is initially installed.

If the dispenser identification 158 is present (yes 166) the system is ready to begin dispensing 168. After confirming the dispenser identification number 158, the program checks the patient database 152 to determine if there are other dispensers 172 for the prescribed medication. If there are no other medication dispensers 16 for the particular medication (no 174), the opioid specific App12 on the patient database 152 is set to allow dispensing 176 according to the prescription instructions 4.

If other medication dispensers 16 for medication therapy are identified (yes 178), the program checks if there are other dispensers 172, and if not 174, the program is ready to begin the dispensing 176 process. However, if there are other dispensers 172 (yes 178), the program proceeds to check if all of the doses 180 in the first medicament dispenser 16 have been dispensed. If the answer is 182, the opioid specific App12 is authorized to dispense 184 from the new or additional drug dispenser 16 as instructed by the prescription 4. If the answer is no 186, i.e., not all of the medication has been dispensed 180 from the first medication dispenser 16: (i) the second or subsequent medicament dispenser 16 remains locked, restricting dispensing until the medicament in the first medicament dispenser 16 is fully dispensed, or (ii) the first medicament dispenser 16 remains locked and allows the second or subsequent dispenser 16 to begin dispensing 188 as prescribed 4. This procedure prevents more than one authorized dose from being dispensed from any one or more of the medication dispensers 16. At the same time, a message/notification 190 is generated informing the patient 6 that the medication in the first medication dispenser 16 needs to be fully dispensed before it expires.

Fig. 5 is a diagram depicting an exemplary embodiment of an opioid specific App12, the opioid specific App12 residing on the interface device 14 or on a separate drug dispenser 16 and controlling the dose of drug dispensed from the drug dispenser 16. When the patient 6 is prescribed opioids, the patient 6 is trained with respect to operating the drug-specific dispensing App12 and associated drug dispenser 16 using the App's training module 236.

In this embodiment of the invention, the opioid specific App12 comprises the following software modules: (i) biometric authentication 202, (ii) prescription information 204 module, which is remotely programmable by the integrated support center 22, (iii) patient reminder 205 module, (iv) interface device API 206 module, (v) patient self-assessment 208 module, which is unique for each medication, (vi) patient self-test 210 module, which is unique for each medication, (vii) patient self-report 212 module, which is unique for each medication, (viii) digital capture (API)214 module, (ix) data collection 215 module. (x) An interface database 216, (xi) a prescriber side-effect tracking preferences 218 module, (xii) a dispensing algorithm 220 module that is unique for each medication and can be personalized for each patient, (xiii) a communications and reports 222 module, (xiv) a central server data synchronization 224 module, (xv) a patient reports 226 module, (xvi) a medication replacement box 227 module, (xvii) a package insert 228, (xviii) a dispenser manual 230, (xix) an opioid-specific App manual 232, (xx) an aid and troubleshooting 234 module, (xxi) a training module 236, and (xxii) a unique App serial number 238.

The following is an exemplary description of the embodiment of fig. 5 of the present invention:

when an electronic prescription is submitted 150 to the patient database 152, it is automatically triggeredApp generation program200. Each of the following modules (which were specific for each drug and each patient) was then initially constructed as an opioid-specific App 12.

Biometric authenticationThe module 202 includes utilizing a biometric authentication screen and/or a digital interface that allows the patient to automatically move to the first medication-specific dispensing algorithm 13 screen after authentication. The biometric authentication 202 may be composed of one biometric authentication method or a combination of more than one biometric authentication method. Examples include the irisScanning systems, retinal scanning systems, fingerprint scanning systems, password entry systems, facial scanning systems, voice scanning systems, gesture recognition systems, automated server generated temporary password systems, and the like.

The biometric authentication 202 may also be used as a diagnostic input that the drug-specific dispensing algorithm 13 may use. For example, an iris scan may be used for biometric authentication 202 and as a digital input for patient self-assessment 208. The opioid specific App12 may use the patient's 6 base and/or trend iris scans to determine changes in pupil size to determine whether the patient 6 exhibits a "pinpoint pupil" or a "dilated pupil," which is indicative of opioid overdose (e.g., opioid overdose). The algorithm will make appropriate adjustments to lighting conditions, distances, etc. and individual pupil dilation characteristics of the patient 6 when making decisions.

As part of the biometric authentication 202 process, after the biometric authentication 202 identifies the patient 6, the program: (i) effecting a handshake/connection with the medication dispenser 16, (ii) checking to ensure that the medication has not expired 103 (its expiration date/expiration date has not been exceeded), (iii) the opioid has been stored within the prescribed temperature 104 and humidity 106 parameters, (iv) checking the prescription 4 information to ensure that the patient 6 is authorized to dispense a dose (the dose is within the prescribed prescription 4 parameters), (v) verifying that the serial number 450 of the medication dispenser 16 has been registered with the patient 6, and then effecting a handshake/connection with a designated digital device to download a specific digitally captured patient value or information 852, 854, 856, 857, 858, 859, 860.

If the biometric authentication 202 cannot identify the patient 6, it asks the patient 6 to try again. After a given number of attempts, it alerts patient 6 to contact integration support center 22 and notifies integration support center 22 of the failed attempt, and if the medication is not properly dispensed within a specified time period, then patient 6 is listed as the subject of the follow-up call by integration support center 22.

If the opioid-specific App12 is unable to identify the drug dispenser 16, the patient 6 gets a notification screen explaining why it is unable to identify the drug dispenser 16, which may include, but is not limited to: (i) failure to locate a medication dispenser 16, (ii) the medication dispenser 16 does not have the correct serial number, (iii) the prescribed medication is not fully dispensed from other medication dispensers 16, etc. Meanwhile, if the opioid specific App12 determines that the drug dispenser 16 does not have the correct serial number 450, it sends a message to the integrated support center 22 indicating the serial number of the identified drug dispenser 16 for the integrated support center 22 to take follow-up action. One option for the integrated support center 22 is to lock the screen of the opioid specific App12, giving the patient 6 only the option of calling the integrated support center 22 to resolve their dispensing problem, and another option is to lock the previous drug dispenser 16 containing the undispensed drug and authorize the resumption of dispensing with the new drug dispenser 16. The process may be automated or programmed to require intervention on behalf of the integrated support center 22.

PrescriptionModule 204 (which is unique to each opioid) includes the ability of the prescriber 2, pharmacy 8, other authorized healthcare professional, or integrated support center 22 to enter some or all of the prescription 4 information. Clicking on submission 150 in the corresponding API interface electronic prescription 4 program (e.g., ADSC MedicsRx, Allsccripts, DAW Systems, DrFirst Rcopia, MDT Toolbox-Rx, Medtab RxCy, OA Systems, Practice Fusion, RxNT eRx, Spectra eRx, etc.) and/or pharmacy prescription program/system (e.g., Omnicare, QS/1, PharMerica, Frameworks, etc.) and/or electronic prescription network (e.g., Surescripts-which seamlessly connects prescriber 2 with pharmacy 8) loads data into patient database 152. Prescription 4 data is then automatically integrated by App generation program 200 into opioid specific App12 and/or any subsequent opioid specific App12 updates. The prescriber 2 and/or pharmacy 8 may enter additional data input through an Application Program Interface (API) and electronic prescribing program/system. When an update is submitted, App generation program 200 automatically synchronizes all inputs and updates patient database 152 and interface database 278 (if an opioid-specific App12 has been previously downloaded onto interface device 14) or stand-aloneOpioid-specific App12 of patient 6 in drug dispenser 16.

When a medication cassette 18 is loaded into the multi-purpose medication dispenser 16, an Application Program Interface (API) enables the pharmacy 8 or other medical professional dispensing the opioid to enter the brand and/or generic name of the desired medication, strength/dose, NDC number, lot number, medication temperature storage range, medication humidity storage range, and expiration date/expiration date of the medication. This input may be done manually and/or by bar code scanning of personalized medicine kit 18.

The prescription information defines the dose intensity and the schedule of administration (e.g., q.d., b.i.d., t.i.d., q.i.d., q.s., q.i.d., q.h.s., x times per day, x times per week, x times per month, q.4h, q.6h, q.o.d., a.c., p.c., prn, etc.). The prn dose and/or, for example, the patient self-analgesic dose can be specified to allow the patient 6 to self-treat to a maximum cumulative dose using a plurality of smaller doses over a specified period of time. Once the maximum dose is dispensed, the drug dispenser 16 is locked by the opioid specific App12 until the next dosing session begins and the patient enters the necessary information to enable the opioid specific App12 to signal the drug dispenser 16 to dispense. This in effect allows "oral patient-controlled analgesia" and/or symptomatic control of certain conditions (e.g., breakthrough pain) by the patient.

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 a patient 6 dose reminder schedule. Reminders include, but are not limited to, the ability of the opioid-specific App12 to notify the patient 6 using different methods. Examples include: (i) automatically displaying the biometric login screen 850 and causing the interface device 14 to buzz, and/or (ii) initiating a phone call with a recorded reminder message, and/or (iii) sending an email message, and/or (iv) sending a short message, and/or (v) causing the integrated support center 22 to call the patient 6, and/or (vi) sending a message to a caregiver or family member if the medication is not being taken, etc. within a specified time after the dose should be taken/dispensed. The order of reminders may be specified for each patient.

The opioid specific App12 is displayed on the screen of the interface device when a medication should be dispensed and/or when a reminder to take the medication is activated. When the interface device 14 (e.g., smartphone) is turned on or unlocked, the screen automatically moves to the biometric authentication 850 screen. If the opioid specific App12 is clicked on the screen of the interface device 14 or on the screen of the stand-alone drug dispenser 16, the biometric authentication 850 screen is opened.

Patient remindersModule 205 uses the dosing frequency 80 to display an opioid specific App12 screen on the interface device 14 or the stand-alone medication dispenser 16 when medication should be dispensed. If the medication is not dispensed within the specified time period, the program causes interface device 14 to vibrate and/or send an email or text message to patient 6 reminding him/her to take the medication. If patient 6 does not dispense medication after the specified time interval, the program sends a notification to the specified and authorized prescriber 118, the disease management personnel 124, relatives 130, 136, 142, etc. If the patient 6 does not dispense medication after the additional time has elapsed, the program sends a notification to the integrated call center 22 to call the patient 6 to determine the reason for his/her non-dispensing of medication.

Interface device APIThe 206 module utilizes the bluetooth and/or Wi-Fi communication capabilities of the interface device 14 and a specially written Application Program Interface (API) to interface, signal/communicate with: the medication dispenser 16, the patient database 152, the integrated call center 22, third party programs (e.g., patient log 852) residing on the interface device 14, and designated, prescription, patient monitoring and/or diagnostic devices intended to capture digital patient values and/or observations 854, 856, 857, 858, 859, 860, and/or the like. These APIs allow the programs and devices to communicate with each other and enable the opioid specific App12 to assemble prescribed information as well as patient information needed by the drug specific dispensing algorithm 13 to make dispensing decisions.

App generation program 200 adds a separate diagnostic and/or monitoring device API from the API library on data server 10 to the opioid-specific and patient-customized App12 only as required by prescription 4. The addition of specific monitoring and/or diagnostic APIs also integrates information into the App manual 232 and training module 236 and initial patient 6 opioid specific App12 setting instructions/requirements.

Self-evaluation routine database compilation from a data server 10 based onPatient self-assessmentThe module 208: (i) a particular opioid requirement, and/or (ii) a prescribed 4-value/information 108, 110 that prescription 2 specifies he/she wants to follow (for better patient management or to manage particular side effects), and/or (iii) capturing Patient Reported Outcome (PRO) information for clinical trials. Opioid-specific self-assessment is based on, for example, the effects of opioid side effects, potential drug interactions, under-and/or over-dosing, efficacy measurements, dosing schedules, opioid intensity, single-drug or multi-drug regimens, effects of weight gain, aging, development of co-morbidities, and the like. Some patient self-assessment 862 screens, for example, include known self-assessment scales (e.g., Wong Baker Faces) to indicate the degree of pain, or include self-assessment screens specific to the development of a particular drug. For example, for opioids, the purpose of the patient self-assessment screen 862 is to quantify the drugs and manage opioid tolerance. The screens may also be those intended to capture patient 6 specific information required by the regulatory agency for subsequent opioid approval and/or for post-market studies.

Self-test routine database compilation from the data server 10 based onPatient self-testThe module 210: (i) a particular opioid requirement, and/or (ii) a prescribed 4-value/information 108, 110 that prescription 2 specifies he/she wants to follow (for better patient management or to manage particular side effects), and/or (iii) capturing Patient Reported Outcome (PRO) information for clinical trials. Patient self-testing 864 of each opioid is specific based on the side effects of the opioid. For example, for opioids, these include, but are not limited to, measurement confusion (fusion), confusion, and/or detection of pinpoint-like pupils. Some patient self-test screens 864, for example, include known self-testsDetecting or containing a self-test screen developed specifically for opioids. Examples include motor skill detection, cognitive impairment detection, or self-photographing for the patient 6 to take his face (the patient 6 ensures that his/her eyes are open), and so forth. For opioids, the goal 864 of the patient self-test screen is to assist patient management to prevent overdosing, underdosing, misuse, abuse, dependence and/or addiction. The screens may also be those intended to capture patient 6 specific information required by the regulatory agency for subsequent opioid approval and/or for post-market studies.

Self-reporting routine database compilation from a data server 10 based onPatient self-reportingThe module 212: (i) a particular opioid requirement, and/or (ii) a prescribed 4-value/information 108, 110 that prescription 2 specifies he/she wants to follow (for better patient management or to manage particular side effects), and/or (iii) capturing Patient Reported Outcome (PRO) information for clinical trials. The self-report 866 screen for each opioid is specific based on the effects of opioid side effects, potential drug interactions, underdosing and/or overdosing, efficacy measurements, dosing schedules, drug intensity, single or multiple drug regimens, effects of weight loss or weight gain, aging, development of co-morbidities, etc. The self-reporting screen 864 may include (i) a well-established reporting scale (e.g., Bristol Stool Index) to indicate whether the patient is constipation or about to constipation, (ii) a report of other drugs taken within a particular time period and/or since the last opioid dose that may cause drug-drug interactions/adverse events, (iii) or symptoms such as sedation, dizziness, nausea, vomiting, etc. For example, for opioids, the goal of the patient self-report screen 866 is to help patient 6 and prescriber 2 manage opioid side effects, prevent opioid side effects, and prevent overdosing. The screens may also be those intended to capture patient 6 specific information required by the regulatory agency for subsequent opioid approval and/or for post-market studies.

Digital capture from data server 10 based onObtaining API routine database compilationDigital Capture (API)The module 214: (i) a particular opioid requirement, and/or (ii) a prescribed 4-value/information 108, 110 that prescription 2 specifies he/she wants to follow (for better patient management or to manage particular side effects), and/or (iii) capturing Patient Reported Outcome (PRO) information for clinical trials. For example, digital capture includes digital information integrated via the opioid-specific App12 by digital capture from, for example, (i) wearable monitoring device 859, (ii) digital scale 858, (iii) third party monitoring apps 852, 880 on smartphones, (iv) handheld diagnostic device 882, (v) lifestyle monitor 884, (vi) digitized home or self-diagnosis 886, (vii) swallowing tracking and/or diagnostic aids, (viii) medication tracking chip, Radio Frequency Identification Device (RFID)856 or self-photography 857, (ix) digital interface 860, and/or caregiver or parent patient assessment and/or journal entry (which may be present in other apps on the interface device 14 of the patient 6), and the like.

Data collectionThe 215 module is designed to aggregate all primary and trend information from the drug dispenser 16, the medication box 18, the other opioid specific App12 module, the patient self-assessment 208, the patient self-test 210, the patient self-report 212, and the digital capture 214 modules, and organize and aggregate the data so that the dispensing algorithm 220 can utilize.

Interface databaseThe module 216 is designed to populate an interface database 278 residing on the interface device 14 or the stand-alone medication dispenser 16 and is designed to store information that is continuously synchronized with the patient database 152. For example, it aggregates and synchronizes the following: patient information: (i) the patient's full name 440, (ii) the patient's street address 442, (iii) the patient's date of birth 444; (iv) logging into the data repository 445; medicament dispenser information: (v) dispenser opening code 446 (contains more than one dispenser code), (vi) tamper-resistant history 448, (vii) dispenser serial number 450 (contains more than one dispenser serial number), (viii) cartridge serial number 452 (contains more than one cartridge serial number), (ix) medication NDC number 454, (x) medication lot number 456 (contains more than one lot number), (xi) medication expiration date 458 (each and every special lot number)Lot number correlated), (xii) drug storage temperature 460, (xiii) drug storage humidity 462, (xiv) time and date of last dose 464, (xv) number of remaining pills 466; prescription information: (xvi) A drug name 468, (xvii) strength 470, (xviii) dosage form 472, (xix) number of drugs prescribed 474, (xx) supplemental authorization 476, (xxi) full name of the prescriber 478, (xxii) national provider id of the prescriber (npi)480, (xxiii) DEA number of the prescriber 482, (xxiv) store (pharmacy) name 484, (xxv) prescription reference number 486, (xxvi) prescription issue date 488; tracking value: (xxvii) Prescription (dosing schedule) 490, (xxviii) digital follow-up value 492, (xxix) self-assessment value 494, (xxx) self-test value 496, (xxxi) self-report value 498, (xxxii) concurrently taken drug 499, (xxxiii) side-effect value 500, (xxxiv) clinical trial information 501; and (3) error reporting: (xxxv) Unsuccessful allocation attempt history 502, (xxxvi) error code history 504; reminding information: (xxxvii) Reminder selection and scheduling 506, (xxxviii) name of the prescriber 508, (xxxix) email 510 of the prescriber, (xl) text messaging telephone number 512 of the prescriber, (xli) name 514 of the disease management person, (xlii) email 516 of the disease management person, (xliii) text messaging telephone number 518 of the disease management person, (xliv) name 520 of the relative No. 1, (xlv) email 522 of the relative No. 1, (xlvi) text messaging telephone number 524 of the relative No. 1, (xlvii) name 526 of the relative No. 2, (xlviii) email 528 of the relative No. 2, xlix) text messaging telephone number 530 of the relative No. 2, (l) name 532 of the relative No. 3, (li) email 534 of the relative No. 3, (lii) text messaging telephone number 536 of the relative No. 3.

Drug side-effect routine database compilation from the data server 10 based onPrescription person side effect tracking Preference(s)218, module: (i) prescriber 2 specifies prescribed 4-side effect information 108, 110 he/she wants to track (for better patient management or managing specific side effects), and/or (ii) captures Patient Reported Outcome (PRO) information for clinical trials. Each of the routines is side-effect specific and is based on the specific side-effects of the opioid determined during the period before and after the start of the clinical trial, such as set forth in the following referencesThe function is as follows: goodman&Gilman's, the pharmaceutical Basis of Therapeutics (12 th edition) (Goodman et al (McGraw-Hill) (2011); and 2015Physician's Desk Reference (PDR); cortex of Thomson road penetration^TMCompetition information; adis R&D; and/or Pharmaprojects by Citeline, et al.

Allocation algorithmThe 220 modules include, for example, a product expiration date (expiration date) 103, appropriately stored information (e.g., temperature, humidity, etc.) 104, 106, one or more patient self-assessments 494, patient self-tests 496, patient self-reports 498, and/or one or more digitally tracked 492 diagnostic or monitored values, an assignment algorithm 13, an assignment screen 868 and interface with the medication dispenser 16, and patient feedback and indication screens 870, 872, 874, etc. The feedback and instruction screens presented are compiled by the App generator 200 from the data server 10 patient feedback and instruction database. The indications are opioid specific.

Communication and reportingThe 222 module includes, for example: (i) an interface between the opioid specific App12 and the drug dispenser 16 via the interface device 14; (ii) an interface between the opioid specific App12 and any proprietary or third party digital devices, data sink devices, computer databases, diagnostic devices, drug tracking devices, and the like (e.g., those digital devices listed in fig. 18, e.g., 852, 854, 856, 857, 858, 859, 860, and those digital devices listed in fig. 19, e.g., 858, 880, 882, 884, 886); (iii) an interface between the opioid specific App12 and the data server 10 and various databases storing information captured by the opioid specific App 12; (iv) data and reports exchanged between the data server 10, the integrated support center 22, accessed by the opioid specific App 12; (v) reminders and notifications issued by the opioid specific App12 and communicated to patient 6, prescribers 2, 508, 512, disease managers 514, 516, 518 and relatives 520, 522, 524, 526, 528, 530, 532, 534, 536 and/or other caregivers, etc.; (vi) the opioid-specific App12 and the Integrated support center 22 are secured according to the health insurance circulation and accountability Act (HIPAA) patient 6 data Security requirementsA handshake/connection; (vii) synchronizing information captured by the opioid specific App12 with the data server 10 of the integrated support center 22; (viii) sending notifications to the integration support center 22 and receiving notifications from the integration support center 22; (ix) enabling the integrated support center 22 to lock or unlock the medication dispenser 16; (x) An abnormal attempt to alert the integrated support center 22 to open the medication dispenser 16; (xi) The ability of the integration support center 22 to remotely update the opioid-specific App12 software; (xii) In the case of opioid recall, the integrated support center 22 is allowed to immediately lock (prevent all dispensing) those drug dispensers 16 containing a cartridge 18, which cartridge 18 contains the recalled opioid and/or opioid lot, and at the same time inform the patient 6 what they need to do; (xiii) Enabling the opioid-specific App12 to access patient 6's reports, charts and graphs requested by the patient 6; (ix) enabling the patient 6 to request that a replenishment prescription be sent to his/her pharmacy 8 for replenishment; (x) Enabling the integration support center 22 to change prescriptions on the opioid specific App 12; (xi) Interfaces between opioid-specific App12 software downloads and update routines, etc. that enable App generation program 200; (xii) Enabling a communication interface between the opioid-specific App12, the drug dispensers 16, and the integrated support center 22 that allows the integrated support center 22 to address issues with the opioid-specific App12 and/or the drug dispensers 16, and so on.

Central server data synchronizationModule 224 is a software module that automatically synchronizes interface database 278 and patient database 152. Examples of data types for synchronization include, but are not limited to: patient information: (i) the patient's full name 440, (ii) the patient's street address 442, (iii) the patient's date of birth 444; (iv) logging into the data repository 445; distributor information: (v) dispenser opening code 446 (contains more than one dispenser code), (vi) tamper-resistant attempt history 448, (vii) dispenser serial number 450 (contains more than one dispenser serial number), (viii) cartridge serial number 452 (contains more than one cartridge serial number), (ix) medication NDC number 454, (x) medication lot number 456 (contains more than one lot number), (xi) medication expiration date 458 for each lot, (xii) medication storage temperature 460, (xiii) medication storage humidity 462, (xiv) last doseTime and date 464, (xv) number of remaining pills 466; prescription information: (xvi) A drug name 468, (xvii) strength 470, (xviii) dosage form 472, (xix) number of drugs prescribed 474, (xx) supplemental authorization 476, (xxi) full name of the prescriber 478, (xxii) national provider id of the prescriber (npi)480, (xxiii) DEA number of the prescriber 482, (xxiv) store (pharmacy) name 484, (xxv) prescription reference number 486, (xxvi) prescription issue date 488; tracking value: (xxvii) Prescription (dosing schedule) 490, (xxviii) digital follow-up value 492, (xxix) self-assessment value 494, (xxx) self-test value 496, (xxxi) self-report value 498, (xxxii) concurrently taken drug 499, (xxxiii) side-effect value 500, (xxxiv) clinical trial information 501; and (3) error reporting: (xxxv) Unsuccessful allocation attempt history 502, (xxxvi) error code history 504; reminding information: (xxxvii) Reminder selection and scheduling 506, (xxxviii) name of the prescriber 508, (xxxix) email 510 of the prescriber, (xl) text messaging telephone number 512 of the prescriber, (xli) name 514 of the disease management person, (xlii) email 516 of the disease management person, (xliii) text messaging telephone number 518 of the disease management person, (xliv) name 520 of the relative No. 1, (xlv) email 522 of the relative No. 1, (xlvi) text messaging telephone number 524 of the relative No. 1, (xlvii) name 526 of the relative No. 2, (xlviii) email 528 of the relative No. 2, xlix) text messaging telephone number 530 of the relative No. 2, (l) name 532 of the relative No. 3, (li) email 534 of the relative No. 3, (lii) text messaging telephone number 536 of the relative No. 3.

Patient reportsThe 226 module includes, for example: (i) the ability of the patient 6 to request certain reports generated by the opioid-specific App12, such as the time the patient 6 last took the opioid, prescription information details, opioid details (e.g., brand and generic name, lot number, expiration date/expiration date, remaining dose, reorder information, drug interactions, typical side effects, etc.); (ii) graphs and charts created by the opioid specific App12 based on information stored by the interface device 14 or the independent drug dispenser 16; and (iii) charts, charts and/or reports created by the data server 10 of the integrated support center 22 for passage by the patient 6Opioid-specific App12 download, and the like.

Medicine box replacementThe 227 module is designed to use the patient identification number 160 and the medication NDC 70 number to prevent the patient 6 from dispensing repeat doses of the same opioid from one or more prescriptions 4 prescribed by one or more prescribers 2 and/or to dispense prescribed doses of opioid 70 from one or more medication dispensers 16 or cartridges 18 containing a particular medication 70 (to eliminate repeat dosing). This procedure is accomplished by prioritizing disposable drug dispensers 16 with integrated cartridges and/or cartridges 18 containing the same opioid 70, such that a given opioid 70 in a disposable drug dispenser 16 and/or cartridge 18: (i) must be fully dispensed as prescribed 4 before the subsequent cartridge 18 can begin dispensing a given medication 70, or (ii) the first single-use medication dispenser 16 or cartridge 18 is designated to lock-out (prevent dispensing) and enable the subsequent single-use medication dispenser 16 or cartridge 18 to dispense a single opioid dose as prescribed 4. This enables dispensing from a plurality of disposable medication dispensers 16 containing the same medication if the disposable medication dispenser 16 is inoperable, lost or left at another location. This also enables multiple cartridges 18 (for the reusable medication dispenser 16) to be used if a particular cartridge 18 is in trouble (e.g., damaged, improperly stored, the original reusable medication dispenser 16 is lost or damaged, etc.). This process enables the prescriber 2 and pharmacy 8 to dispense sufficient opioid doses to limit the number of mail order shipments (within the state/government prescription guidelines) between pharmacy 8 visits and/or refills.

Packaging instructionThe 228 module takes the corresponding opioid's package insert in the appropriate language (specified according to the language preferences of patient 6) from the drug package insert database on the data server 10 and incorporates it into the opioid specific App 12.

Dispenser manualThe 230 module retrieves the corresponding medication dispenser 16 manual in the appropriate language from the medication dispenser manual database on the data server 10 and incorporates it into the opioid specificApp 12.

App manualThe 232 module obtains the corresponding opioid specific App12 manual in the appropriate language from the opioid specific App manual database on the data server 10 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 containing the drug specific dispensing algorithm 13 and the prescriber 2 prescribed 4 and defined digital capture, self-assessment, self-test and self-report data capture and screen specifications and their respective troubleshooting specifications.

Help and troubleshootingThe 234 module is an artificial intelligence based query based module that allows the patient 6 to enter keywords or phrases to call up a list of potential parts that may solve the problem for the patient 6. The portion of the special help and troubleshooting screen on the individual drug dispenser 16 or interface device 14 that is appropriate on the opioid specific App12 is hot-linked (hotlinked) to allow viewing of instructions without interrupting the patient 6 to enter the dispensing sequence. The base module is capable of answering most questions. However, a link to help and troubleshooting the extended version hosted on the central server 10 is provided in each screen. The central server 10 also hosts user groups to allow the patient 6 to ask questions of other users and issue recommended improvements and/or enhancements to the opioid-specific App12 and/or corresponding drug dispenser 16 and/or support services, etc. Links to video tutorials on video sharing websites (e.g., YouTube, Vimeo, etc.) are also provided.

Training module236 includes, for example, (i) hot links to allocator and App manuals 230 and 232 and training and troubleshooting video libraries residing on training video databases on data server 10; (ii) video and/or other consumer video services, such as those published on YouTube, Vimeo, including all aspects of using and troubleshooting the opioid specific App12 and corresponding drug dispensers 16, (iii) step-by-step tutorials present on the interface device 14, (iv) a hot-link "help" button on each respective screen to allow the patient 6 to call up the respective screenInstructions are used without interrupting the order of entering the desired information or selecting particular commands, etc.

Similar medical professional training modules are available to assist the medical professional/prescriber 2/pharmacy 8 in addressing all of the issues associated with each respective medication dispenser 16, medication cassette 18 and troubleshooting documentation or software issues. These files and videos that exist on the central server 10 may be accessed, for example, on popular video sharing websites (e.g., YouTube, Vimeo, etc.).

When the App generator is ready to complete the compilation of the personalized opioid specific App 240, it specifiesUnique App serial number of238。

The personalized opioid specific App 240 is then linked to the patient identification number 160. Thereafter, patient specific opioid specific App 12: (i) is compiled; (ii) stored in an opioid-specific App database on the data server 10, and (iii) automatically transmitted to the patient 6 in a download email and/or text message. Patient 6 clicks on a link on an email or text message or pastes a link in a browser to enter the download screen, where patient 6 clicks on download App 246 to download the opioid specific App 12.

The patient identification number 160 links the patient 6 with the patient-specific opioid-specific App 12. Patient 6 uses patient identification number 160 to set a biometric entry 250 on the first visit to the opioid specific App 12.

The opioid-specific App12 utilizes, for example, the features, memory, and computing capabilities of the interface device 14; (i) facilitating the interaction of the opioid-specific App12 with the patient 6, (ii) interacting with the medication dispenser 16 using the bluetooth and/or Wi-Fi communication capabilities of the interface device 14, (iii) interacting with the data center 10 and the integrated support center 22 using the internet communication capabilities thereof, (iv) sending notifications to the patient 6, prescriber 2, 508 other caregivers, patient 6, disease manager 514, and/or family members 520, 526, 532 using the email and text messaging capabilities thereof, (v) calling the integrated support center 22 using a telephone, (vi) playing user instructions, troubleshooting, medication and disease information videos using the video player capabilities, (vii) capturing lifestyle information using the GPS capabilities thereof (if positioning is required), (viii) storing the opioid-specific App12 using a memory of the interface device 14, Prescription 4, dispensing history 464, tamper alert history 448 (etc.), and recent patient 6 input information and screen responses 494, 496, 498, 499, 500, 501 and digitally captured information 492 which are used to make dispensing decisions by the medication specific dispensing algorithm 13 or which are requested to be captured for future use by the prescriber 2 or other medical professional 108, 110, (ix) his speech recognition and communication functions, etc.

The use of the interface device 14 allows the medication dispenser 16 to: (i) smaller than otherwise; (ii) the manufacturing cost is low; (iii) reducing battery power requirements, etc. These above listed functions or combinations thereof are integrated into the disposable medication dispenser 16 as well as the stand alone medication dispenser 16.

Fig. 6 is an exemplary embodiment of a biometric authentication interface designed to comply with the health insurance currency and accountability act (HIPAA) or any governmental agency setting standards for protecting sensitive patient data. This means that all required physical, network and process security measures are in place and followed and are incorporated herein by reference.

When the patient 6 clicks on the opioid specific App12 for the first time, it initiates the set biometric login 250 screen. It asks the patient 6 to enter the patient identification number 160, which was previously emailed or texted to the patient 6, into the patient identification number 252 entry box. It then establishes the language preferences 253 of patient 6 and allows patient 6 to select (if preferred) the conversational interface preferences 253 of the opioid specific App 12. It then requests: (i) the patient's full name 254, (ii) the patient's street address 256, (iii) the patient's phone number 258 (which is the phone number that calls for the mobile phone/interface device 14 or the stand-alone medication dispenser 16), and (iv) the patient's email address 260 (which accommodates one or more email addresses). Thereafter, it enters a routine to capture biometric authentication reference information for one or more of: (v) fingerprint scan 262, (vi) face scan 264, (vii) iris scan 266, (viii) voiceprint 268, (ix) technical support password 270, (x) technical support challenge problem 1272, and (x) technical support challenge problem 2274. Once the biometric login 276 is established, the opioid specific App12 saves the biometric login information in a login data repository in the interface database 278. At this point, the opioid specific App12 is ready to begin authorizing the drug dispenser 16 to dispense the drug.

Thereafter, when the patient 6 clicks on the opioid specific App12 or clicks on the reminder screen 250, a biometric login 280 screen appears. If the biometric login 280 is unsuccessful (no 282), the patient 6 is asked to try again. After a specified number of attempts, patient 6 is given an indication of troubleshooting. The troubleshooting instruction includes clicking a call button to connect patient 6 to integrated call center 22. If biometric login 280 is successful (yes 284), opioid specific App12 automatically attempts to handshake with all designated digital monitoring devices 286. If successful (yes 292), the opioid specific App12 downloads the specified information to the interface database 278. If digital handshake 286 is unsuccessful (no 288), then the opioid specific App12 retries to effect handshake. If the handshake cannot be achieved after a specified number of attempts, it stops the attempt and sends a notification message 290, and then makes an attempt to achieve handshake 302 with the medication dispenser 16. If the biometric login 280 is successful (yes 284), the routine attempts to signal exchange with the medication dispenser 302 at the same time as attempting to signal exchange with the digital device 286. If successful (yes 304) the unit is ready to pass through the drug specific dispensing algorithm 13 screen to allow the drug dispenser 16 to dispense an opioid dose. If the handshake with the medication dispenser is unsuccessful (no 294 or no 296), the routine will try two more times to effect the handshake. If the third (3 rd) attempt is unsuccessful (no 298), the routine displays an unsuccessful handshake indication 300 screen telling the patient 6 how to resolve the problem.

Fig. 7 is an exemplary embodiment of the logic flow and processes associated with loading an opioid cartridge 18 into a reusable medication dispenser 16. This process is not applicable to tamper-resistant disposable medication dispensers 16, which disposable medication dispensers 16 contain an integrated drug cassette 18 and cannot be opened after loading the drug cassette 18 into a subsequently sealed disposable medication dispenser 16. The following description is an example of how a health care professional may load a restricted opioid cartridge 18 into the reusable drug dispenser 16. (for drugs whose transfer, addiction, dependence, misuse, abuse, etc. are not a concern, patient 6 may follow a similar but less restrictive routine to load drug cassette 18 into reusable medication dispenser 16.)

To load the pill box 18, the medical professional opens his/her electronic prescription 4 screen for the prescribed 4 medications and then plugs the USB cable from the Rx computer into the medication dispenser 16. Alternatively, a USB cable may be plugged in from a computer with the necessary software to enable entry of the necessary code required to open the medication dispenser 16.

The USB cable provides power to the separate flip lock and unlock mechanisms 1028, 1030 of the medication dispenser. The power for the flip cap locking and unlocking mechanisms 1028, 1030 is not available from the batteries of the medication dispenser 16.

After the program confirms that the dispenser identification number 158 assigned to the medication is the same (corresponding) to the dispenser identification number 158 contained in the medication dispenser's firmware 352, the medication dispenser 16 may be opened to allow loading of the medication cassette 18. If the dispenser identification number 158 on the firmware of the medication dispenser 16 is blank because this is the first time the medication dispenser 16 is used for the medication, then the program inserts the dispenser identification number 158 into the medication dispenser's firmware 352.

Dispenser identification number 158 cannot be copied into interface database 278 of opioid specific App 12. It is copied and retained in the dispenser opening code 446 data repository residing in the patient database 152 stored in the data server 10.

The USB cable is the same cable used to charge the batteries in the rechargeable battery-equipped reusable medication dispenser 16.

If the dispenser identification number 158 is the same as the code in the dispenser firmware 352, the program performs a handshake with the medication dispenser 316 and attempts to open the medication dispenser 318. If it cannot open the medication dispenser (no 320), the program restarts the dispenser opening routine 310. The program checks if there is sufficient battery charge 323 before unlocking the reusable medication dispenser 16. If the answer is no 324, the program requires that the batteries be replaced or the device be recharged 326 to a minimum level before allowing the drug cassette 18 to be loaded 330 into the reusable drug dispenser 16.

The temperature within the cavity of the drug cassette 18 within the drug dispenser 16 is monitored during recharging to ensure that it does not exceed the allowable drug storage temperature 104. If temperature 104 is within one degree of maximum storage temperature 104, for example, recharging is stopped until the temperature in the storage cavity of cartridge 18 returns to an acceptable recharge temperature range prior to charging.

If there is sufficient battery charge or if the battery charge has returned to a sufficient battery charge level (yes 328), the cartridge 18 may be loaded 330 into the reusable medication dispenser 16. If this is the initial cartridge 332 for the medication (yes 334), the program updates the medication information on the firmware 336 of the medication dispenser. If this is not the initial cartridge 18 dock for the drug (no 338), the program confirms that the correct drug according to prescription 4 is in cartridge 340 by comparing the prescription drug in prescription 4 with the drug indicated in firmware 352. If not (no 342), the program provides a troubleshooting indication 344. If the correct medication is in the cartridge (yes 346), the program copies the cartridge serial number 348 and links it with the medication dispenser serial number 350 on the opioid specific App12 that is present in the interface database 278. Then, synchronization is started: (i) an appropriate time and date 354, (ii) a drug expiration date 356, (iii) an appropriate storage temperature range 358, (iv) an acceptable humidity range 360, (v) a number of available pills 362, and then (vi) clear the dispensing history of all values on the firmware 364 except for the date and time of the last dispensing, and (vii) clear the firmware tampering sensor history 366, and (viii) ensure that the same data is contained on both the drug dispenser 16 firmware 352 and the opioid specific App12 interface database 278. At this point, the serial number of the medication box 18 and the serial number of the medication dispenser 16 are linked together 370 on the opioid specific App 12. At this point, the opioid-specific App12 data is synchronized 372 with the patient database 152 on the data server 10. If immediate synchronization cannot be achieved, the program stores the information for synchronization the next time a connection is available.

Fig. 8 is an exemplary embodiment describing the synchronization and updating of data between three opioid-specific App 12-related databases, (i) the patient database 152 residing on the centralized data server 10, (ii) the dispenser database 380 that is part of the opioid-specific App12 residing on the interface device 14 or on an independent drug dispenser 16, and (iii) the dispenser firmware 352 in each drug dispenser 16.

When loading of the drug cassette 18 into the reusable drug dispenser 16 is complete, signal exchange is achieved between the drug dispenser 16 and the opioid specific App 12. Upon identifying the presence of a new cartridge 18, the opioid-specific App12 links with the patient database 152 and begins a data update process to ensure that the corresponding data is synchronized and up-to-date. First, the program synchronizes and updates the dispenser database 380 data 382, 384, 386, 388, 390, 392 and effects any updates 394 from the dispenser database 380 to the patient database 152. The update program 394 then synchronizes and updates the dispenser firmware 352, 396, 398, 400, 402, 404, 406, 408, 410, 412, 414, 416, 418, 420, 422, 158, 160, 424, and 426 using the patient database 152. Any changes more recently in the dispenser firmware 352 are updated on the patient database 152. This sequence is repeated whenever the patient dispenses a dose, or if an internet connection is not available, once an internet connection is established between the interface device 14 or Wi-Fi enabled stand-alone medication dispenser 16 and the data server 10.

FIG. 9 is an exemplary embodiment of a database file that is synchronized when the synchronize data 430 routine of 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, the personalized opioid specific App12 is fully updated and ready for dispensing 432.

Fig. 10 is an exemplary embodiment of an interface database 278 type of data and data file/database that is continuously synchronized with patient database 152. The opioid specific App12 data contained in the interface device database 278 is synchronized in real time with the centralized patient database 152. The interface database 278 retains information for a determined period of time to enable the drug-specific dispensing algorithm 13 and/or the App's prescribed 4-patient 6 value and side-effect reporting routines to use and present trend data while minimizing memory requirements of the drug dispenser 16 and the opioid-specific App 12. The patient database 152 residing on the data server 10 maintains an ongoing history without deleting previous patient data.

The following is representative of the type of data file that is synchronized: patient information: (i) the patient's full name 440, (ii) the patient's street address 442, (iii) the patient's date of birth 444; (iv) logging into the data repository 445; distributor information: (v) dispenser open code 446 (contains more than one dispenser code), (vi) tamper attempt history 448, (vii) dispenser serial number 450 (contains more than one dispenser serial number), (viii) cartridge serial number 452 (contains more than one cartridge serial number), (ix) medication NDC number 454, (x) medication lot number 456, (xi) medication expiration date 458 (one expiration date reserved for each batch of medication), (xii) medication storage temperature 460, (xiii) medication storage humidity 462, (xiv) time and date of last dose 464, (xv) number of remaining pills 466; prescription information: (xvi) A drug name 468, (xvii) strength 470, (xviii) dosage form 472, (xix) number of drugs prescribed 474, (xx) supplemental authorization 476, (xxi) full name of the prescriber 478, (xxii) national provider id of the prescriber (npi)480, (xxiii) DEA number of the prescriber 482, (xxiv) store (pharmacy) name 484, (xxv) prescription reference number 486, (xxvi) prescription issue date 488; trackingThe value: (xxvii) Prescription (administration schedule) 490, (xxviii) numerical follow-up values¹³492, (xxix) self-assessed value 494, (xxx) self-detected value 496, (xxxi) self-reported value 498, (xxxii) concurrently administered drug 499, (xxxiii) side-effect value 500, (xxxiv) clinical trial information 501; and (3) error reporting: (xxxv) Unsuccessful allocation attempt history 502, (xxxvi) error code history 504; reminding information: (xxxvii) Reminder selection and scheduling 506, (xxxviii) name of the prescriber 508, (xxxix) email 510 of the prescriber, (xl) text messaging telephone number 512 of the prescriber, (xli) name 514 of the disease management person, (xlii) email 516 of the disease management person, (xliii) text messaging telephone number 518 of the disease management person, (xliv) name 520 of the relative No. 1, (xlv) email 522 of the relative No. 1, (xlvi) text messaging telephone number 524 of the relative No. 1, (xlvii) name 526 of the relative No. 2, (xlviii) email 528 of the relative No. 2, xlix) text messaging telephone number 530 of the relative No. 2, (l) name 532 of the relative No. 3, (li) email 534 of the relative No. 3, (lii) text messaging telephone number 536 of the relative No. 3.

Fig. 11 is an exemplary embodiment of the opioid specific App12 logic. When patient 6 activates the opioid specific App 540 by clicking on the App or by responding to a dose expiration reminder, the screen automatically moves to the biometric login 250 screen. After successful biometric authentication, the program checks if the product has expired 542, if it is 544, presents a product expired patient screen notification 552, and if replenishment is approved, automatically sends a replenishment request to the pharmacy 554. At the same time, the program locks the medication dispenser 546, updates the patient database 548, and notifies the integrated call center 550. If the product has not expired (no 556), then a check is made as to whether the product has been stored at the correct storage temperature since the last dispensing of the product 558.

If the medication is not stored at the correct storage temperature (no 560), an incorrect storage temperature patient screen notification 562 is presented and if replenishment is approved, a replenishment request is automatically sent to the pharmacy 554. At the same time, the program locks the medication 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), a check is made as to whether the product has been stored at the correct humidity range since the last dispensing of the product 566.

If the medication is not stored at the correct moisture level (no 568), an incorrect stored moisture patient screen notification 570 is presented and if replenishment is approved, a replenishment request is automatically sent to the pharmacy 554. At the same time, the program locks the medication 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), the time and date of the last dose and the dispensing history 574 are checked to establish the basis for checking the necessary information required to authorize the dispensing.

FIG. 12 is an exemplary embodiment of prescription information that is programmatically checked before authorizing dispensing of a dosage of medication. The program checks whether the prescription request is within the prescription 4 time between indications of doses 580, and if not 581, the program issues a patient reminder 582 indicating when the next dose is available. If the time interval is within the prescription guidelines (yes 583), the program checks if the maximum daily dose has been exceeded 584. If the maximum number of daily doses has been exceeded (yes 585), the program issues a patient reminder 586 indicating that a request for exceeding the prescribed maximum number of daily doses is requested and indicating when the next dose is available. If the maximum number of daily doses has not been exceeded (no 587), the program checks if the longest authorized number of dosing days 588 has been exceeded, i.e., the number of days the prescription is valid. If 590, a patient alert 592 is issued indicating that the prescription period has expired and instructing the patient 6 to contact the prescriber 2 if he/she has any problems. If the maximum number of authorized days for administration has not been exceeded (no 594), the program has determined that it is approved for dispensing 596 by prescription 4 and assembled the digitally captured patient 6 information.

FIG. 13 is an exemplary embodiment of a program routine for aggregating digitally captured information from third party devices via an application programming interface API. For example, information may be gathered from: patient 6's smartphone (e.g., a diary of meals, pressure, oxygen saturation, heart rate, other medications taken, and bluetooth-connected drug dispenser information, etc.), wearable monitors (e.g., a smartwatch, a sports monitor, a holter monitor, an electrocardiogram, an RFID chip tracker, a wearable diagnostic monitor, etc.), external monitoring and diagnostic devices (e.g., a scale, a diagnostic device, clothing (clasping), a pill dispenser, etc.), a bridge and hub (e.g., Verily's bridge), and an RFID chip whose API interface allows signals to be obtained and data to be stored in interface database 278 of opioid-specific App12, then in patient database 152 on data server 10, and so forth.

Each tracked interface has its own API. The program is organized to aggregate data in order, e.g., it goes through all smartphone App APIs (more than one may be specified) before going to wearable monitor APIs (more than one may be specified), and so on.

The program begins collecting data-captured patient 6 information by: access to correspondingSmart phone App API600 to access and assemble specified information, access data 602. If the data is successfully accessed (yes 604), the program accesses the interface database 278 and enters the value into the numeric tracking value database 492. If the data is not accessible (NO 606), an error report 608 is created, an e-mail is created and sent to patient 6 for patient consultation correction 610, interface database 278 is accessed and error report 608 is entered into error code history 504 database. It then proceeds to the next smartphone App API, or if no longer indicated, to wearable monitor API 612.

It accessesWearable monitor API612 to access and assemble specified information, and then access data 614. If the data is successfully accessed (yes 616), the program accesses the interface database 278 and enters the value into the numeric tracking value database 492. If the data is not accessible (NO 618), an error report 620 is created, a patient consultation correction step 622 email is created and sent to patient 6, interface database 278 is accessed and an error is correctedThe report 620 is entered into the error code history 504 database. It then proceeds to the next wearable monitor API or, if no longer indicated, to the external monitor API 624.

It accessesExternal monitor API624 to access and aggregate the specified information, and then access data 626. If the data is successfully accessed (yes 627), the program accesses the interface database 278 and enters the value into the numeric tracking value database 492. If the data is not accessible (NO 628), an error report 630 is created, a patient consultation correction step 632 email is created and sent to patient 6, interface database 278 is accessed and error report 630 is entered into error code history 504 database. It then proceeds to the next external monitor API or, if no longer indicated, to the RFID chip API 634.

It accessesRFID chip API634 to access and assemble the specified information, and then access data 636. If the data is successfully accessed (yes 637), the program accesses the interface database 278 and enters the values into the numeric tracking value database 492. If the data is not accessible (NO 638), an error report 640 is created, an email is created and sent to patient 6 to patient consult correction step 642, interface database 278 is accessed and error report 640 is entered into error code history 504 database. It then proceeds to the next external monitor API or, if no longer indicated, to the patient self-assessment input screen 624.

Fig. 14 is an exemplary embodiment of a program that captures patient self-assessment, patient self-testing, and/or patient self-reported physiology, psychology, lifestyle, medications taken since last opioid dose and/or medications taken at the same time, and/or environmental information/values via a prescribed patient 6 input screen on the opioid specific App 12. The data may be requested as follows: (i) by the drug-specific dispensing algorithm 13, or (ii) specified by the prescriber 2 when filling the prescription 4, or (iii) required by regulatory agencies for regulatory approval of drugs if the product is in a clinical trial phase. The number of screens displayed must be carefully weighed against the value of the data collected. The specific data screen may be presented each time the patient 6 wants to dispense a dose, or may be presented on a predetermined schedule or in response to a digitally captured value or patient 6 input value/information.

The program is organized to assemble the data in a sequence, for example, it passes through all patient self-assessment screens (more than one may be specified) before going to a patient self-test screen (more than one may be specified), and then goes to a patient self-report screen (more than one may be specified). The following represents examples of respective data collection logics.

After the RFID chip API routine is completed, program entryPatient self-assessment input650 screen. Before presenting the specified screen, it checks the request schedule 652. If a screen is specified, it presents the screen and requests patient input 654. If the patient 6 is able to enter his/her information (yes 656), the program accesses the interface database 278 and enters the values into the self-assessed values database 494. If the information cannot be captured (NO 658), an error report 660 is created, interface database 278 is accessed, and an error code is entered into error code history 504 file. At the same time, it creates and presents a patient indication 662 on the interface screen of the interface device 14 or the stand-alone medication dispenser 16 and prompts the patient 6 to begin the patient input process again. Once the value is added to the self-assessed values database 494, the program proceeds to the next designated patient self-assessment routine and, if no longer needed, to the patient self-test input screen 664 routine.

In the exhibition ofPatient self-test input screenBefore 664, the program routine checks the request plan 666. If a screen is specified, it presents the screen and requests patient input 668. If the patient 6 is able to enter his/her information (yes 670), the program accesses the interface database 278 and enters the values into the self-test value database 496. If the information cannot be captured (No 672), an error report 674 is created, interface database 278 is accessed, and an error code is entered into error code history 504 file. At the same time, it creates and presents patient indication 678 on the interface screen of interface device 14 or stand-alone medication dispenser 16, and prompts patient 6 to re-administer medicationThe patient input process is again initiated. Once the value is added to the self-test value database 494, the program proceeds to the next designated patient self-test routine and, if no longer needed, to the patient self-report entry screen 680 routine.

In the exhibition ofPatient self-report entry screenBefore 680, the program routine checks the request plan 682. If a screen is specified, it presents the screen and requests patient input 684. If the patient 6 is able to enter his/her information (yes 686), the program accesses the interface database 278 and enters the values into the self-reporting values database 498. If the information cannot be captured (no 688), an error report 690 is created, interface database 278 is accessed, and an error code is entered into error code history 504 file. At the same time, it creates and presents patient instructions 692 on the interface device 14 or the stand-alone medication dispenser 16 interface screen and prompts the patient 6 to begin the patient input process again. Once the value is added to the self-reporting value database 498, the program proceeds to the next designated patient self-reporting routine and, if no longer needed, to the patient concurrently taking medication input screen 700 routine.

Fig. 15 is an exemplary embodiment of a procedure for capturing clinical trial information for drugs, side effects and/or patient reports concurrently taken by patients on a designated opioid specific App12 data capture screen as requested: (i) by the drug-specific dispensing algorithm 13, or (ii) specified by the prescriber 2 when filling the prescription 4, or (iii) required by regulatory agencies for regulatory approval of drugs if the product is in a clinical trial phase. The number of screens displayed must be carefully weighed against the value of the data collected. The specific data screen may be presented each time the patient 6 wants to dispense a dose, or may be presented on a predetermined schedule or in response to a digitally captured value or patient 6 input value/information.

The program is organized to assemble data in a sequence, for example, it passes through a drug entry screen 700, for example, where the patient takes at the same time, then a side effect tracking 712 screen, then a patient reported clinical trial data 724 screen. The following represents examples of respective data collection logics.

After completing the input screen for patient self-assessment and/or patient self-testing and/or patient self-reporting, the program displaysMedicine input screen for patient to take simultaneously700 and requests patient input 702. Patient 6 is able to enter his/her information (yes 704) the program accesses interface database 278 and enters the value into concurrently taken medication database 499. If the information cannot be captured (NO 706), an error report 708 is created, the interface database 278 is accessed, and an error code is entered into the error code history 504 file. At the same time, it creates and presents a patient indication 710 on the interface screen of the interface device 14 or the stand-alone medication dispenser 16 and prompts the patient 6 to begin the patient input process again. Once the values are added to the self-reporting value database 499, the program enters a side-effect tracking 712 input routine according to the prescriber's request.

The program showsSide effect tracking based on prescriber request712 input screen and request patient input 714. If patient 6 is able to enter his/her information (yes 716), the program accesses interface database 278 and enters the values into side-effect tracking database 500. If the information cannot be captured (No 718), an error report is created 720, the interface database 278 is accessed, and an error code is entered into the error code history 504 file. At the same time, it creates and presents patient indication 722 on the interface screen of interface device 14 or stand-alone medication dispenser 16 and prompts patient 6 to begin the patient input process again. Once the value is added to the side-effect tracking database 500, the program enters a patient reported clinical trial information 724 entry routine.

The program showsPatient reported clinical trial information724 input screen and requests patient input 726. If the patient 6 is able to enter his/her information (yes 728), the program accesses the interface database 278 and enters the values into the clinical trial information database 501. If the information cannot be captured (No 730), an error report is created 732, interface database 278 is accessed, and an error code is entered into error code history 504 file. At the same time, it creates and dispenses either at the interface device 14 or a separate medicationThe patient indication 734 is presented on the interface screen of the device 16 and prompts the patient 6 to begin the patient input process again. Once the value is added to the clinical trial information database 501, the program enters the assignment algorithm 740 routine.

Fig. 16 is an exemplary embodiment of the logic followed by allocation algorithm 740. Any information requested or aggregated by the prescriber for clinical trial data capture that is not required by the medication-specific dispensing algorithm 13 is not considered in making the dispensing decision. The algorithm cycles through the digitally captured values to the patient entered data to the concurrently administered medication information in order to make the dispensing decision.

The process of assignment algorithm 740 begins by checking each of the digital capture values to see if they are within range 742. The routine loops 744 through each selected value to determine if they are within a predetermined acceptable range 746. If the answer is no 748 for any value, the program locks the medication dispenser 546, issues a patient reminder 750 to the patient 6 and any other persons listed as individuals who should be reminded, notifies the consolidation call center 752, and updates the unsuccessful dispensing attempt history 502. If all of the digital capture values are within the acceptable range (yes 756), the program proceeds to check the patient entered data.

The program examines the corresponding patient 6 self-assessment, self-test and self-reporting input data to determine if the data is acceptable 758, and then through each selected input cycle 760 to determine if they are within a predetermined acceptable range 762. If the answer is no 764 for any value, the program locks the medication dispenser 546, issues a patient reminder 766 to the patient 6 and any other person listed as an individual who should be reminded, notifies the integrated call center 768, and updates the unsuccessful dispensing attempt history 502. If all self-assessment, self-test and self-report values are within acceptable ranges (yes 772), the process proceeds to check the log of concurrently taken medications.

The logic then examines the new list of concurrently taken medications 774 and passes through each of the selected medication cycles 776 to determine if there are potential interactions 778 that could lead to adverse drug-drug mediated adverse events. If the answer is no 780 for each new medication, the program prepares to dispense 782, displays a ready to dispense notification 786 on the screen of the interface device 14 or the stand-alone medication dispenser 16, and then synchronizes the interface and patient database 788 to indicate that the dispensing of the medication dose is approved on the particular date and time (the program automatically adjusts for the time travel variance of the patient on travel). This information, along with the date and time the medicament dispenser 16 dispensed the dose, may be used to determine if there may be a transfer of medicament. However, if a potential medication-medication interaction is flagged (yes 790), the program locks the medication dispenser 546, issues a patient alert 792 to the patient 6 and any other persons listed as individuals who should be alerted, notifies the integrated call center 794, and updates the unsuccessful dispensing attempt history 502.

Fig. 17 is an exemplary embodiment of the classification flow from the patient 6 contacting the integrated support center 22 through problem solving. The classification is organized into three main types of patient 6 support calls: dispenser handling, administration issues, and medical issues.

Each of the patient reminders 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 the individual medication dispensers 16 includes an auto-dial option to immediately contact the integrated call center 22 to resolve the dispensing issue. The email and sms alert contain an explicitly indicated integrated call center 22 call number.

When the patient 6 calls 14 the integrated call center 22, the security program of the call center initiates the patient authentication routine 800. If the integrated call center does not initially identify the patient 6 (no 802), it has available alternatives to verify the identity of the patient 6 in the HIPPA privacy rules, thereby protecting the individual's case and other personal health information.

Once the identity of the patient 6 is verified (yes 804), the call center representative reviews the patient 6 profile generated by the call center software (which extracts the patient 6 information from the patient database 152 residing on the data server 10) to help categorize 806 the patient 6's support request into a dispenser operation 808 issue, a medication administration issue 820, or a medical issue 834/issue. If multiple problems exist by themselves, the representative follows the sequence from dispenser problem 808 to administration problem 820 to medical problem 834. An exemplary problem solving sequence follows.

To solve the dispatcher operation 808 problem, the representative defines a question, selects the question on her/his support screen and begins to ask some typical questions 810 to narrow the query. After sufficiently narrowing, he/she checks the error code history 504, the unsuccessful allocation attempt history 502, and then enters the troubleshooting interface 812. The troubleshooting interface 812 allows the representative to select a different troubleshooting screen 814 to troubleshoot the information with the patient. Each screen is linked to a reference and user manual 230, 232. After the problem is resolved, the representative will prepare a file email 816 to be sent to the patient 6, defining the problem and how to resolve the problem. The email may contain attachments from the reference/user manual 230, 232. The representative updates her/his comments 818 in the patient record.

To solve the dosing problem 820, a drug dispensing history 822 and certain patient values 824 representing the opioid specific App of patient 6 are first examined. S/he then selects the appropriate advice screen 826, which is designed to help and guide the representative how to proceed. They provide a decision tree that relates to any decision on whether to do the following: (i) lock 828 the medication dispenser 16, (ii) lock the medication dispenser 16 until the patient 6 negotiates with their prescriber 2 and/or physician 828, or (iii) unlock the medication dispenser 16 and allow it to dispense a dose 828. Thereafter, the representative records the content in question and how the problem is solved in the email 830 sent to the patient 6. The patient record 818 is then updated, if necessary, to notify the prescriber 832 of the occurrence, and again, if necessary, to update the electronic medical record 24 of the patient 6 residing on the data server 10.

To solve the medical problem 834, a representative enters his typical medical problem 836 screen for a particular opioid and/or pain type. The representative selects the appropriate subject from the screen and checks the appropriate advice or classification script 838 to determine if s/he should advise the patient 6 or transfer the patient to the call center physician. If the representative can suggest patient 6 (yes 840), the representative discusses the issue with the patient and makes certain suggestions (suggests patient) 842. Thereafter, the representative updates the patient record 818, if appropriate notifies the prescriber 832, and again, if appropriate, updates the electronic medical record 24 residing on the data server 10.

If the call center screen indicates that the representative is classifying the patient (no 844), the representative transfers the patient 6 to the appropriate call center physician (or appropriate joint healthcare professional) 846. The doctor advises the patient 6 or turns the patient 6 back to his caregiver 848. Thereafter, the doctor updates the patient record 818, notifies the prescriber 2 and/or any other designated caregivers 832, and updates the electronic case 24 of the patient 6 that exists on the data server 10.

Fig. 18 is an exemplary embodiment of a flow chart of an opioid-specific App12, a standard prescription biometric authentication 850 login, a collection of digitally captured information 852, 854, 856, 857, 858, 859, 860, a patient self-assessment 862, a patient self-test 864, a patient self-report 866 input screen, and a medication dispensing patient 6 screen 868, 870, 872, and 874 controlled by a medication-specific dispensing algorithm 13. The exemplary embodiment is a patient 6 interacting to dispense an opioid (e.g., oxycodone/APAP,hydrocodone, hydrocodone/APAP, hydromorphone, oxymorphone, morphine, buprenorphine, etc., such as abuse deterrents, immediate release, sustained release, extended release, combinations, prodrugs, etc.) as a pharmaceutical.

The process starts with the medication dispensing App12 reminding the patient 6 that he/she should take his/her medication. If the medication dispensing App12 is present on the smartphone, the medication dispensing App12 graphic automatically switches to the biometric authentication screen 850 when the patient 6 unlocks the phone. Alternatively, the patient 6 can click on the opioid specific App12 at any time. Clicking on the opioid specific App12 screen displays a biometric authentication 850 screen. When the patient 6 is authenticated, (i) the opioid specific App12 effects a signal exchange with the medication dispenser 16 and any digital device for which an Application Programming Interface (API) has been written, (ii) checks to ensure that the medication has not expired 458 or exceeded its expiration date/prescription expiration date 103, (iii) confirms that it has been stored within the temperature 104, 460 and humidity 106, 462 storage parameters, (iv) checks the prescription to ensure that the medication can be dispensed within the prescription guidelines 70, 72, 74, 80, 82, 84, 86, then (v) moves to the patient self-assessment screen 862. Clicking on the response value 862 on the patient 6 self-assessment screen automatically moves to the next self-assessment screen (if needed) or automatically moves to the patient 6 self-test screen 864. Completing the patient 6 self-test automatically moves the process to the patient 6 self-report 866 screen. After completing the self-reported message, the medication specific dispensing algorithm 13 processes the various inputs.

If nothing is found by the medication-specific dispensing algorithm 13 to prevent dispensing, the patient 6 will see a dispensing screen 868. By clicking on, for example, the medicament dispenser 16 dispense button, the patient can dispense a dose with a single click, after which the medicament dispenser 16 returns to the locked position unless the prescription allows the patient to dispense some doses on a PRN basis without waiting between doses. If the prescription is a PRN, the medication dispenser 16 is locked after dispensing the designed number of doses over a specified period of time. If the patient 6 wants to change the previous entry before dispensing, he/she can return to the correct screen and change the selection using the device scroll back function. If the medication-specific dispensing algorithm 13 finds any reason for not allowing a dispense, it selects from the appropriate medication-specific screen to display the reason for the dispense being denied and to facilitate the ability of the patient 6 to utilize the appropriate medication support 870, 872, 874.

Exemplary embodiments of the patient self-assessment screen 862, the patient self-detection screen 864, and the patient self-report screen 866 include, for example, a self-assessment pain metric scale 862 adapted from Wong bakers Faces; self-detect motor skill detection 864; a self-reported Stool consistency observation (a widely accepted Stool measure) 866 from Bristol Stool Scale was used. These are examples of screens that may be used in an embodiment as input to the medication specific dispensing algorithm 13 to decide whether to dispense. A scale may be created, adapted or integrated to capture desired patient reporting information. In addition to use with the drug-specific dispensing algorithm 13, these may be used, for example, to quantify opioids, monitor enhanced tolerance, measure drug efficacy, for better patient management, to better manage drug-mediated side effects, for preventative health (e.g., to avoid or actively manage drug-mediated side effects), for clinical trials and/or for post-market surveillance, and the like.

This embodiment is suitable for use in, for example, clinical trials, post-market supervision, risk assessment and mitigation strategy (REMS) planning for the FDA, and controlling and ensuring that a drug is effective and safe when dispensed within the drug-specific dispensing algorithm 13 as part of a prescribed drug regimen, among other things. The opioid-specific App12 may be configured to capture all patient self-assessment, self-testing, and/or self-reporting information required by the FDA, EMA, or other similar governmental agencies for approving opioids or regulating opioid compliance. The only difference from the standard drug specific algorithm 13 is that an additional input screen is required. The same drug specific dispensing algorithm 13 (decision tree) will be used for normal and clinical trial prescription.

Fig. 19 is an exemplary embodiment of the digital capture information 859, 858, 880, 882, 884, 886, and illustrates the type of digital information and other digital information captured on the interface device 14 (e.g., smartphone) (e.g., log, medication list, stress monitoring, heart rate, SpO2, diet, exercise, blood pressure, electrocardiogram values, ambient temperature, altitude, etc.), which may be collected and integrated into the decision tree logic by the corresponding medication specific allocation algorithm 13 (as shown in fig. 12-16). The availability of disease-specific apps and related disease or condition-specific digital health information is rising rapidly, such that the example in fig. 19 requires not only disease information, but also physiology, psychology, lifestyle, diagnosis, medications taken, digital medication intake, diagnostic and tracking equipment, and environmental input, among others.

Fig. 20 is an illustration of an exemplary embodiment of the medicament dispenser 16. There are many different permutations, from a fully disposable tamper-resistant disposable drug dispenser 16 controlled by the opioid specific App12, to a reusable drug dispenser 16 controlled by the opioid specific App12, to a stand-alone drug dispenser 16, where the opioid specific App12 is incorporated into the stand-alone drug dispenser 16, and so on. In addition, each medication dispenser 16 may be configured with one medication to multiple medications. The following and fig. 20, 21, 22, 23, 24, 25, 28, 29 and 30 are examples of functions integrated into the new system and design alternatives available. The illustration shows a reusable drug dispenser 16 controlled by the opioid specific App12 as it represents the most complex drug dispenser 16 iteration, while the disposable drug dispenser 16 shows the least complex drug dispenser 16 design.

The reusable drug dispensers 890, 892, 894, 896, 898, 16 are designed to: (i) controlled by the opioid specific App12 present on the interface device 14, (ii) water resistant, (iii) tamper resistant, (iv) drop and/or impact resistant, rugged, (v) capable of operating at and withstanding high and low temperatures within a defined temperature range, (vi) reusable, (vii) rechargeable and/or battery replaceable, and (viii) small enough to fit in a trouser pocket or purse. The reusable medication dispenser 16 automatically identifies medications based on the medication specific cartridges 18, 900 docked into the reusable medication dispenser (16). In the safest configuration, which is designed to limit drug accessibility by healthcare professionals, not authorized dispensed doses, the cartridges 18, 900 can only be docked or removed by healthcare professionals. The reusable medication dispenser 16 remains locked from dispensing unless it receives an encrypted signal from the authorized opioid specific App 12. Only one click is required and the drug dispenser 16 dispenses the opioid dose.

When interfaced through digital signal exchange with the opioid specific App12, the reusable medication dispenser 16 communicates, for example: (i) its serial number (of the medication dispenser), (ii) medication information on the medication cassette 16, 900, (iii) the current temperature and historical temperature tracked over time since the last dispense, (iv) time tracked humidity exposure since the last dispense, (iv) the date and time of the last dispensing of medication, and any date of unauthorized attempts to open or tamper with the medication dispenser 16.

Fig. 21 is an exemplary embodiment illustration showing the dimensions of an exemplary design of a minimum medication dispenser 904 and the ability to increase the height 896 or width 894, 910 of the medication dispenser 16 to accommodate more pills and/or larger pills and/or a second or more medication boxes 18. The width may also be extended to accommodate the dispensing of two or more different drugs, each of which is present in its own cartridge 18. Individual cassettes may also accommodate multiple drug regimens, so long as each drug is filled in a separate drug well to prevent cross-contamination.

Figure 22 illustrates a layout of different medicament dispenser configurations and designs with different features and benefits, each designed to meet specific patient 6 and medicament specific requirements. Each easy to operate, with shared biometric login and assignment buttons, and some with interface screens.

For example, the dispensing control 920 configuration is a stand-alone medication dispenser without external communication functionality, which is only designed to control: (i) access via biometric login, (ii) dispensing on a prescribed schedule, and (iii) loading of the drug cassette 18 by a healthcare professional only, if desired. It may also incorporate some or all of the functionality presented in the various embodiments by reference.

Prescription compliance 930 the individual medicament dispenser has all the features of the dispensing control 920 medicament dispenser as well as Wi-Fi, internet and/or bluetooth communication capabilities to enable e-mail of selected reminder communications to the patient 6, determined caregiver and/or family member. The device has a large interactive screen to enable the use of the opioid specific App12 to control data aggregation, input, email communication, drug dispensing, and the like. A thicker version of the standalone device may add some phone functionality that would provide all of the functionality of the patient management 940 system for that version, but with a separate dispenser configuration. It may contain some or all of the functionality shown in the various embodiments.

The patient management 940 configuration includes a medication dispenser 16 controlled by an opioid specific App12 located on the interface device 14. It has all the functionality of the independent distributors 920, 930 and may contain some or all of the functionality presented in the various embodiments by reference.

FIG. 23 is a graph of using, for example, various dose strengths and pill sizes 960Are shown in the figures of exemplary embodiments of different kits 960, 18a, 18 b.Different cartridge sizes and configurations are required, and depending on the number of pills required for a prescription, the larger of the two illustrated medicament dispensers 904, 896 may be required. Each cartridge 18, 18a, 18b, 900 is designed to: (i) use of approved medication packaging materials, (ii) docking into the medication dispenser 18, 920, 930, 940, and (iii) as a blank box that can hold a number of different pills, tablets, capsules, etc. within a specified size range. The blank cartridges 900, 18a, 18b are designed to be specific to the medication dispenser 16, 920, 930, 940. Each labeled as part of an automatic cassette filling operation to allow the medication dispenser 16, 920, 930, 940 to identify the medication contained in the medication cassette 18, 18a, 18b, 900 (either for an individual medication in the cassette or for each of a plurality of medications in a single medication cassette 18, 18a, 18b, 900; or for the multi-medication cassette 18 in each respective multi-medication dispenser 1002, 1004, 1006, 1008). Each linked to: (i) drug name (brand and/or generic name) 400, (i)i) NDC number 402 of the drug, (iii) lot number 456 of the drug, (iv) expiration date 458/expiration date of the drug, etc. The labeling of the drug cassette 18 is intended to meet all drug label regulatory requirements.

Fig. 24 illustrates an exemplary embodiment of a patient 6 specific chart 970, 972 illustrating the relationship between the time a patient 6 takes a medication and his/her self-assessed, self-tested, self-reported or digitally captured symptoms and/or diagnostic values. This clearly shows the relationship between drug and pain management 970 and drug and symptom/side effect management 972. The patient 6 may request and view charts or forms on the interface device 14 or the stand-alone medication dispenser 16 designed to guide the patient 6 and promote prescription compliance and persistence for the patient 6.

The prescriber 2 may use this information to ensure that the drug is effective for the individual patient 6, dose, personalize pain therapy, and manage opioid tolerance (for personalized medicine).

Corresponding charts, graphs, reports, etc. may be generated by the centralized analysis platform 10 and/or the opioid specific App12 of the integrated support center 22 residing on the data server 10.

Figure 25 is an exemplary embodiment of a medicament dispenser designed to meet the needs of most patients 6. About half of all patients 6 take two drugs and 20% take five or more drugs. The incorporated therapy App 1000 auto-senses other drug-specific apps on the interface device 14, e.g., 980, 982, 984, 986, 988. It incorporates two to multiple opioid-specific apps 12 into one user interface for all medications, eliminating duplicate logins, entries, and record keeping. Which in turn digitally signals the multi-drug dispenser 1002, 1004, 1006, 1008 and controls the dispensing of each individual drug using a respective drug-specific dispensing algorithm 13. Furthermore, it coordinates the dispensing schedule so that there is as little dispensing time as possible in the corresponding prescription. The multiple medication dispensers 1002, 1004, 1006, 1008 eliminate concerns about when which medication must be taken.

Illustrations 1002, 1004, 1006, 1008 are examples of dispensing units containing two medicaments to five medicaments. These units are independent or may be docked into a multi-dispenser desktop unit dispenser.

Fig. 26 is an exemplary embodiment of an integrated IT system 1010 that associates a medication dispenser 16, an opioid-specific App12, and an interface device 14 with: (i) a data server 10, (ii) a database, and (iii) an analysis system 10 to ensure that the patient 6 receives optimal care tailored to the patient 6 with respect to the prescribed medication ("personalized medicine").

All data collected by the opioid specific App12 from the drug dispensers 16, 920, 930, 940, the digital capture information 852, 1012, 856, 857, 858, 859, 860, 880, 882, 884, 886, the patient self-assessment screen 862, the patient self-test screen 864, and the self-report screen 868 contained within the opioid specific App12, and the corresponding output of the drug specific dispensing algorithm 13, are communicated by the opioid specific App12 through the interface device 14 (or internet connection of a separate drug dispenser) to the appropriate patient 6 database residing on the data server 10. The data is used to update the corresponding patient screen used by the integrated support center 22. The data is also made available to the corresponding drug registry 1016 and associated electronic medical records 24. Any information that needs to be communicated with patient 6 and/or prescriber 2 is automatically processed by patient management software or by the integrated support center 22.

The information of the patient 6 is continuously analyzed by an analysis routine that includes analyzing the patient 6 individually and comparing it to treatment data from other similar patients to determine if any changes to the therapy may be needed. The integrated support center 22 utilizes this analysis function to assist the prescriber 2 in attempting to plan treatment for difficult patients. The analysis 10 performed may include data of the patient 6, aggregated patient information, and information from electronic cases 24 (either on the data server 10 or in an external database), clinical studies, publications, and the like.

As another example of this embodiment, the data server and analytics 10 provide the following and other exemplary skeletal support:

for theSpecial App for opioids12: (i) assigning an App to a particular patient 6, (ii) linking the drug dispenser 16 to the opioid-specific App12, which in turn limits the dispenser and App to work only in concert with each other, (iii) storing the opioid-specific App12 code on a server, (iv) issuing, storing and linking a patient identification number 160, and (v) enabling and updating the opioid-specific App12 software through communication with the interface device 14, among other things.

For theMedicament dispenser16: (i) issue, store, and link the dispenser identification number 158, (ii) store all reported data in a database designated on the data server 10, and synchronize patient data on all corresponding interface devices 14 (smart phones, tablets, computers, individual medication dispensers 16, 920, 930, 940, etc.); (iii) storing dispensing, dispensing attempt, lock-out and failure data reported by the drug dispenser 16 by the opioid specific App12 and the interface device 14; (iv) the report is delivered to patient 6 by opioid specific App12 as required; (v) enabling lock or unlock transmissions from the integration support center 22; (ii) modifying the prescription 4 on the integrated support center 22 representative of the input opioid specific App12 according to the prescription person 2 and/or the instructions of authorized healthcare professionals, and (vi) storing the authorized healthcare professional identification code required by the professional to open the drug dispenser 16 to change the medication cassette 18 or load the medication cassette 18 into the reusable drug dispenser 16, etc.

For theIntegrated support center22: (i) aggregating patient 6 data, (ii) presenting and updating data on the patient 6 specific integrated support center 22 screen, (iii) providing the ability to change the prescription of the patient 6, (iv) enabling remote locking and unlocking of individual drug dispensers 16 by their opioid specific App12, (v) enabling drug specific delivery to all patients 6, (vi) enabling simultaneous locking of specific drugs in the event of a drug recall(vii) a medicament dispenser 16, and (vii) enabling a healthcare professional to open, load, and close the reusable medicament dispenser 16 (if so indicated, the patient 6 is prohibited from opening the tamper-resistant reusable medicament dispenser 16), and so forth.

For thePatient's health6: (i) preparing patient-specific communications, (ii) creating personalized charts and reports, (iii) generating "payer results reports", and REM reports as needed, etc.

For theRegistration form1016: (i) maintaining registry 1016, electronic case 24 and opioid specific App12 databases and analytics, (ii) preparing treatment outcome reports, (iii) preparing best practices reports, and (iv) providing patient 6 specific diagnostic and treatment assistance to prescribers 2 through integrated support center 22, via integrated support center 22 representatives or via HIPPA compliance access to certain databases that data servers 10 may query on demand.

For theThose who prescribe a prescription2: (i) preparing and sending patient 6 reminders, (ii) performing metadata analysis, preparing patient 6 specific reports and sharing results with the prescriber 2, (iii) providing assistance/guidance to the prescriber 2 through the integrated support center 2 based on database and analysis queries requested by the prescriber 2, and (iv) preparing best practices reports based on patient 6 and electronic medical record 24 metadata analysis, etc.

For theElectronic medical record24: (i) interfacing with the electronic medical record 24, (ii) updating patient 6 distribution, compliance, and persistence information, (iii) updating digitally captured and patient entered physiological, psychological, lifestyle, concurrent medication and environmental data collected by the medication-specific App12 required by the medication-specific distribution algorithm 13, required by the prescriber 2 to request tracking, and/or clinical trial data submission, (iii) updating any integrated support center 22 recommendations annotations, and (iv) extracting patient 6 data within HIPAA guidelines for metadata analysis, etc.

Fig. 27 is an illustration of an exemplary embodiment of how the integrated support center 22 interfaces with the opioid specific App12, the patient 6, the prescriber 2, and the electronic medical record 24.

The interaction of the integrated support center 22 with the patient 6 may be initiated by some scenarios and take many different forms. Examples include, but are not limited to: (i) receiving patient 6 reminders from the patient's opioid-specific App 12; (ii) patient 6 calls; (iii) answering questions from the patient 6 regarding the medication dispenser 16, the opioid specific App12, the medication or pain treatment thereof; (iv) support patient 6 recommendations within the central guideline; (v) locking individual patient's medication dispensers 16 based on: (a) an opioid-specific App12 reminder, (b) an integrated support center 22 analysis reminder, (c) a patient 6 session, etc.; (vi) unlocking the medication dispenser 16 of the individual patient 6 based on: (a) a session with patient 6, (b) a session with prescriber 2, etc.

Further, as an example, the integration support center 22 provides: (i) "compliance" and "compliance" support; (ii) outbound patient 6 phone call; (iii) patient 6 monitoring; (iv) emailing the prescriber 2 and/or physician of the patient 6 and/or calling the prescriber 2 and/or physician of the patient 6, suggesting a change in therapy, etc.; (v) patient 6 disease management education; (vi) ensuring that patient 6 is able to obtain his medication; (vii) collaborate with payers on demand to obtain coverage of high cost medications; (viii) finding a prescription financial assistance plan; (ix) patient 6 education and re-education; (x) Patient 6 follow-up, and (xi) medical business support.

The interaction of the integration support center 22 with the prescriber 2 may be initiated by some scenarios and take many different forms. Examples include, but are not limited to: (i) locking or unlocking a particular patient's medication dispenser 16; (ii) changing the prescription 4; (iii) patient 6-specific physician support uses the data server and analytics 10 of the integrated support center 22 to determine patient-specific treatment alternatives; (iv) assisting in specific data analysis of the patient 6; (v) providing disease/condition specific information; and (vi) medical transaction support, etc.

Fig. 28 is an illustration of an exemplary embodiment of an assembly and locking mechanism for a flip-top design of the disposable medication dispenser 16. The interior of the top of flip 1020 includes a hinge that joins with a hinge on the inside of bottom flip interior 1034. These hinges lock together with hinge pins 1022, the hinge pins 1022 passing through holes in the respective hinges, much the same as the hinges that are joined together on the most common access door hinges.

The top 1020 and bottom 1034 flaps are locked together by a locking bar 1028 that is moved using a micro-actuator. When the top and bottom flaps are closed, the locking bar is pulled down by the micro-actuator and the male members of the hooks mate into corresponding female apertures on the lock button 1030.

The design includes integrated supports to ensure the integrity and durability of the design. They also help to add strength, adding anchors to the internal components of the respective disposable medication dispenser 16 as needed.

This design eliminates the ability to open the disposable medication dispenser 16 to unlock the micro-actuator 1028 without an authorization signal. Top cover 1026 is adapted to close the top of bottom flap 1034. The top 1026 of the top cover covers the top of the hinge pin 1022 and holds it in place. The bottom cover 1036 covers the bottom of the hinge pins 1022 and provides a resting point for the bottom of the hinge pins 1022 and holds it in place.

The right interior portion of the top cover 1026 provides an interface for the end of the locking bar 1028 and allows it to be supported as it moves up and down as needed to lock or unlock. The bottom cover 1036 provides a base that supports the micro-actuator 1028, which micro-actuator 1028 locks and unlocks the flip cover by moving the locking bar 1028 up and down.

The top cover 1026 and bottom cover 1036 are secured to the bottom flap interior 1034 by screws and/or glue that hold each piece together securely from the inside (without external screws). The device then forms a ridged bottom flip platform 1034 to interface with the top flip interior 102. When the medicament dispenser 16 is closed, it forms a strong tamper-resistant housing for the medicament cartridge 18, 18a, 18b, 900.

In one design embodiment, to provide the necessary downward pressure to ensure that the device is both waterproof and dustproof and to facilitate its robust design, the medication dispenser 16 has a latch 1032 designed to apply a desired level of pressure on the respective closed flap 1020, 1034 connection to protect design integrity.

In this example, the top 1024 contains a one-click dispense button. Bottom cap 1038 includes a dispensing port. In the example shown in fig. 22, the top cover and the bottom cover are hermetic housings. Dispensing is accomplished by clicking a combination biometric entry, screen and dispense button on the lower front center of each medication dispenser 16. When dispensing is authorized and the dispense button is clicked, dispensing is achieved by a drawer that opens to the left at the bottom of the medication dispenser 922, 932, 942. When the one-click dispense button is pressed, an alternative design of dispensing may also be achieved by dispensing from the bottom of the medication dispenser 16.

Another example includes a disposable medication dispenser 16. The housing on the disposable medication dispenser 16 is a sealed device where there is no access after the cartridge 18 with the prescribed opioid is docked into the disposable medication dispenser 16 and the housing components are combined using glue or a laser to form a unified housing. Drug dispensing is controlled by the opioid specific App 18. The assignment is made by clicking on the assignment button. The medicament is dispensed at the bottom of the disposable medicament dispenser 16 or through some downstream area or dispensing drawer. After dispensing the opioid, the dispenser opening is covered by an intrusion prevention closure from the interior of the disposable medication dispenser 16. This creates a disposable enclosure that can only be penetrated by breaking the dispenser enclosure, which triggers a tamper alert to the integrated call center 22.

Fig. 29 is an exemplary embodiment and feature schematic of the electronics of the medicament dispenser 16. The system of the medication dispenser 16 includes an application processor 1048, the application processor 1048 including unit firmware, individual medication dispenser 16 serial numbers, and manages all functions. The main unit components are: (i) a communications connection 1042 module, (ii) its data transfer capability 1046, (iii) unit sensors and/or applications 1044 that allow the unit to authenticate a user, sense attempts to tamper/open without authorization, measure drug storage temperature and humidity, time-stamp actions or events (clock function), and locate the unit via GPS; (iv) a display module 1050; (v) a power management and charging system 1056; (vi) memory management 1054; (vii) a cassette controller 1040 enabling dispensing and having the ability to read specific cassette information; (viii) a dose dispenser system 1052; (ix) various components designed to facilitate and protect different system functions 1058, etc.

Fig. 30 is an exemplary embodiment of the placement of electronics and mechanical components external and internal to the disposable medication dispenser 16. The front of the disposable medication dispenser 16 contains an on/off button 1064 that the user can press when the opioid specific App12 is in signal exchange with the medication dispenser 16 if the medication dispenser 16 is not automatically turned on. When handshaking is achieved or the on/off button 1064 is pressed, the blue LED light is on 1066. If the device is ready for dispensing, the LED light 1066 turns green; if the device waits to assign a permission, the LED light 1066 turns yellow; if the device is locked, the LED light 1066 turns red and is not dispensed. The display 1068 is located in the center of the front view of the disposable medication dispenser 16.

Some components are mounted on top clamshell interior 1060; these components include: (i) an on/off button 1064 on the front of the disposable medication dispenser 16 and a switch 1070(ii) on the inside 1060 of the flip top cover) an LED status light 1066LED and electronics 1074; (iii) battery, power management, Wi-Fi, bluetooth, GPS and antenna systems 1072; (iv) LED screen 1068 and its electronics and management system 1076; and (v) a medicament dispensing actuator arm and dispensing lock 1078. The bottom flap interior 1062 contains: (vi) click the assign button 1080; (vii) logic, control elements, processors and memory boards and their various components 1082; (viii) temperature and humidity sensors 1084; (iv) attempting to tamper with sensor 1090; (x) Cassette dispensing motor and controller 1088; (xi) A medicine cartridge reader 1086; (xii) (xiii) a flip lock micro-actuator controller 1094, and (xiii) a dispensing door controller 1092.

Figure 31 is an exemplary embodiment of the correlation of opioid plasma levels and pupil size using oxycodone as an example. Each opioid had its own relationship of pupil size and plasma levels. Pupil size, when normalized to individual patients, can be an indicator of opioid plasma levels. The pinpoint pupil is a hallmark of opioid overdose, but not specifically symptomatic (e.g., a pontine lesion of hemorrhagic or ischemic origin may produce similar results). Due to hypoxia in the case of opioid overdose, significant mydriasis can occur rather than miosis. Thus, pupil size can be used as an indicator of overdose screening.

For example, the relationship between plasma levels of oxycodone and analgesic response depends on the age, health status, medical condition of the patient, the extent of prior opioid treatment, and the concurrent medication that may affect pupil dilation. The minimum effective plasma concentration of oxycodone to achieve analgesia varies widely between patients, particularly among patients who have previously been treated with potent agonist opioids. Thus, patients need to be treated with individually quantified oxycodone doses to achieve the desired effect. Due to increased pain and/or development of tolerance, the minimum effective analgesic concentration of oxycodone for any individual patient may increase with repeated dosing.

A 1100 depicts the time course of pupil diameter over a 24 hour period (pilot study) for 4 subjects receiving oral doses of oxycodone of 10mg, 15mg and 20 mg. Inset 1102 depicts the linear relationship of the area under the effect curve (AUEC) of 3 dose versus pupillary response in individual subjects. It indicates that: within the time frame after the oxycodone dose (applicable to all opioids), there was a maximum percent (%) change in pupil diameter from baseline.

B1104 shows: individual time courses of pupil diameter for 16 subjects after a 15mg dose of oxycodone (gray line) in both the pilot and main studies. This shows the range difference between individuals. It shows that: at normal doses, the pupil does not become a "pinpoint-like pupil", either excessive or mydriatic. The black line represents the mean pupil diameter over time. Thus, the personalized patient 6 baseline may be used as a basis for future pupil size comparisons to determine that the patient 6: (i) whether overdose was taken, (ii) whether it is likely that another opioid dose would become overdose if taken, and (iii) whether it is within a normal range and should be allowed to take an opioid dose.

Fig. 32 is an exemplary embodiment of how a pinpoint-like pupil and a dilated pupil are used as diagnostic indices. Oxycodone pharmacokinetic-pharmacodynamic model prediction of pupil diameter (line) and observation data (squares) shown in 4 representative subjects 1106, 1008, 1110, 1112 receiving 15mg oxycodone demonstrated diagnostic accuracy. The goodness of fit of oxycodone was demonstrated by the four patients on the observed data by the parent drug balance model. High correlations were also detected on the multi-dose data. The results were not significantly different from the estimates obtained with the 15mg dose.

Measuring pupil size using images captured by an iris scan biometric login or an opioid specific App12 login enables setting of a pupil diameter opioid plasma level curve over a time baseline against which future pupil size measurements may be compared. Samsung, Apple, Microsoft, LG, HP, Fujitsu, Vivo, ZTE, Alcatel, UMI, etc. are incorporating iris scans into smartphones. Measuring the pupil using an iris scan ensures that the patient's pupil is measured and provides further security against opioid transfer.

The pharmacokinetic-pharmacodynamic opioid baseline profile for patient 6 may be established by: pupil size measurements were made prior to taking the first opioid dose, and then at specified time intervals during the opioid-specific App12 setup procedure. Thereafter, any statistically significant indicator of a shift from baseline may require a validated set of pupillary measurements and/or a reminder of the integrated support center 22.

After personalization (required for individual differences and for drugs taken simultaneously), the algorithm may use pupil diameters below or above a certain pupil diameter to prevent dispensing of a dose. The effect of using the prediction curve and subsequent doses to determine whether the patient remains within a safe range can be used to allow a dose to be dispensed. If the range falls between the safe dispensing range and the no-dispense value, confirmatory testing can be used to guide the dispense or no-dispense dosage decision, regardless of whether the prescription otherwise allows for dosing. (the integrated support center may have access to this information to help guide their decision.) doses below or above a certain pupil diameter will not be dispensed.

Fig. 33 shows an exemplary embodiment of the present invention, which explains what is the eyelid 1120, iris 1122, pupil 1124 and sclera 1126 of the eye. It shows the difference in eye expansion under intense light 1128 and low light 1130.

Fig. 34 is an exemplary embodiment of a method for detecting, authenticating, and capturing iris and pupil data to make an assignment or unassignment screening decision.

Eye image capture 1140 is accomplished, for example, by a dedicated iris camera and IR (infrared) LED present on the smartphone. The camera is designed with a special image filter that receives and recognizes the reflected image of the iris through a red ir led lamp.

The setup process basically involves lifting the phone to eye level, holding a distance, and waiting for the phone to capture iris data. It can detect which part of the image is the iris and then remove the rest of the information, such as the eyelids, pupil and sclera (white area). Once the iris is registered, the handset stores the iris data as an encrypted piece of code in the database 1156. Thereafter, when the user attempts to access the cell phone, or a drug-specific application containing a dispense or no-dispense pupil algorithm, the LED and camera work together to capture the iris, then extract the file and compare the image to the code to allow access 1158.

Once the image of the eye is captured 1142, the program detects the iris and eyelid 1144 and then extracts the iris region 1146. The program then removes any eyelid artifacts 1148 before normalizing the iris 1150. The pupil detection program then normalizes the pupil regions 1150, 1152.

Normalization uses the size of the iris with the baseline of the pupil stored in database 1156. This allows the pupil size to be adjusted for differences in the distance from the camera to the iris 1140. The digital luminance values enable luminance adjustments to be made to correlate pupil size with luminance and normalize pupil size relative to a baseline.

The standardized data is then translated into a format that can be utilized by the certified 1158 patient-specific program to compare the values to the determined standardized patient-specific pupillary constriction and dilation data ranges to make an assignment or unassign decision 1160.

Fig. 35 is an exemplary embodiment of pupil size logic for making an allocation or non-allocation decision. The process begins with a smartphone iris scan 1160 with authentication 1162 of the correct patient accessing the system. If the patient is not authenticated (no 1164), he/she needs to try 1160 again until authenticated (yes 1166). The program then accesses the normalized pupil measurement 1168 and determines if the pupil is greater than, for example, 8 mm. If 1172, then the decision is to not allocate 1174. If the pupil is less than 8mm (No 1176), the algorithm determines if the pupil is less than, for example, 2.5mm 1178. If the pupil is not less than 2.5mm (no 1180), then the decision is to dispense 1182. However, if the pupil is less than 2.5mm (1184), then the algorithm checks if the pupil size is less than 2.0mm1186 and if 1188, decides not to assign 1174. If the pupil is not less than, for example, 2.0mm (no 1190), the algorithm checks the patient's pupil size against the patient's historical pupil size to determine if this is within a historical baseline or if the pupil size is rapidly decreasing 1192 relative to historical pupil size values. If 1194, then the decision is to not allocate 1174. If the answer is no 1196, the pupil size has not decreased rapidly relative to historical benchmarks (some of which may be obtained from iris scan data used by the patient to access their smartphone, etc. over a period of time), then the program confirms that the pupil size is between 2.0mm and 2.5mm 1198, for example. If 1200, the program performs a validation test 1202, which validation test 1202 aims to reduce false positives (i.e., not to distinguish betweenA false determination of a match). In this example, we self-detect using motor skills. However, other values associated with drug-mediated physiological or psychological changes may be utilized. Examples include, for example, pupil responsiveness to light, pulse rate, blood pressure, heart rate, body temperature, sleep quality, gait, balance, speech patterns, tone, eye movement, specific diagnostic value, CO₂Saturation, respiration rate, etc. Some may perform digital capture (passive monitoring) by devices that do not require a trigger response from the patient, such as wearable monitors (e.g., FitBit), implantable monitors, wearable diagnostics, consumable diagnostics, smart watches, smart phones, and the like.

Another basis for making a partitioning or non-partitioning decision is the standard deviation from the pharmacokinetic-pharmacodynamic opioid baseline curve of patient 6.

The value used to determine whether an oxycodone dose should be dispensed may be based on a change in the normalized pupil size relative to a determined pupil size that is equal to or greater than a defined amount. It may also be a combination of fixed numbers, e.g. for mydriatic and/or tip-like pupils and changes from baseline, both applicable. The aim is to avoid patient 6 taking a dose that would result in an excessive amount of opioid.

Fig. 36 is an exemplary implementation of three-screen 1210, 1212, 1214 motion self-detection. Each screen contains three points randomly placed on the screen. Each point is a different random color. A random point is solid and designated as the point that must be clicked. The title on each screen also randomly changes position and color. Based on the program logic, it is determined whether the patient's cognition is sufficient to dispense an opioid dose or to prevent the opioid from being dispensed (no dispensing 1174) based on motor skill self-testing. The logic behind the motor skill self test is to measure response time and accuracy from the baseline test values to determine if the response time and accuracy are sufficiently degraded to require a rejection 1174 of the assignment decision.

Fig. 37 is an exemplary embodiment of motor skill self-test logic for making dispense or no dispense opioid dose decisions. When the first motor skill detection 1 screen 1220 is presented, it asks the patient 6 to click on the solid dots 1222. If 1226 does not respond after 5 seconds (no 1224), screen 1220 of motor skill test 1 is refreshed with the new button color and position and the test start time is reset to zero. If there is still no response after 5 seconds on the second attempt (no 1224), the program sets the unchecked value to 1(1228) and sets the start time to the actual time minus 3 seconds (1230) and proceeds to the next screen 1238. If the patient 6 clicks on the screen or solid circle 1222 (yes 1232), the program instructs the patient to click on the solid button 1(1234) or the non-clicked solid button 0 (1234). The program then sets the start time to the actual time 1236 and then proceeds to the next inspection screen 1238.

When the motor skill test 2 screen 1240 is presented, it asks the patient 6 to click on the solid dot 1242. If 1246 does not respond after 5 seconds (no 1244), screen 1240 of motor skill test 2 is refreshed with the new button color and position and the test start time of skill test 2 is reset to zero once. If there is still no response after 5 seconds on the second attempt (no 1244), the program sets the unchecked value to 1(1248), makes a decision to not dispense the opioid dose 1174 and stops the algorithm. If the patient 6 clicks on the screen or solid circle 1242 (yes 1250), the program instructs the patient to click on the solid button 1(1254) or the non-clicked solid button 0 (1254). The program then sets the start time to the actual time 1254 and then proceeds to the next test screen 1256.

When the motor skill detection 3 screen 1258 is presented, it asks the patient 6 to click on the solid dot 1260. If 1264 does not respond after 5 seconds (no 1262), screen 1258 of motor skill test 3 is refreshed with the new button color and position and the test start time of skill test 3 is reset back to zero once. If there is still no response after 5 seconds on the second attempt (no 1262), the program sets the unchecked value to 1(1266) and sets the start time for skill detection 3 to the actual time minus 5 seconds (1268). If the patient 6 clicks on the screen or solid circle 1260 (yes 1270), the program instructs the patient to click on the solid button 1(1272) or the non-clicked solid button 0 (1272). The program then sets the click time to the actual time 1274 and then enters the allocate/no allocate logic 1276.

Fig. 38 is an exemplary embodiment of a motor skill detection logic with or without dispensing an opioid dose. The logic begins with the following problem: whether the patient hit the center point exactly, total 3 (1280). If the answer is no 1282, the formula checks if the total click value is equal to 2 or 3 (1284). If no 1286, then a decision is made to not dispense an opioid dose 1174.

If the patient 6 accurately hits the solid point 1280 (which is 1288), the decision is to dispense 1182 opioid dose if the total time to hit the solid point is 1290 seconds, e.g., 1290 (e.g., the time minus the baseline must be equal to less than 2 seconds) if the total time to hit the solid point is, e.g., equal to or less than 2 seconds longer than the baseline detection and/or detection series response. If the answer is no 1292, then the decision to not dispense 1174 an opioid dose.

Fig. 39 is an exemplary embodiment of an opioid dispensing algorithm aimed at reducing the number of false positives (e.g., no dispensing decisions). In this case, if the pupil scan decision is to dispense 1182, then the decision is to dispense the opioid dose 1182.

However, if the result of pupil scan 1160 is to perform a confirmatory test 1202, in this case motor skill self-tests 1210, 1212, 1214, then the result of the confirmatory self-test would be to dispense 1182 or no 1174 opioid dose.

There may be more than one validation experiment. For example, the opioid confirmation test may include one or more digitally captured diagnostic and/or biomarkers, such as pupil responsiveness, respiration rate, oxygen saturation, changes in body temperature, activity level, amount of sleep/nap, heart rate, blood pressure, gait, dizziness, constipation, weight changes, and the like. Certain physiological and/or psychological self-assessment, self-testing or self-reporting information/observations, and the like may also be included.

FIG. 40 is an exemplary embodiment of algorithm logic directed to reducing the number of false positives (e.g., no assignments). It is first determined 1300 whether the pupil diameter is within a normal range of, for example, 2.5mm to 8 mm. If 1302, then the program indicates that medication 1182 should be dispensed. If the answer is no 1304, the program determines whether the patient has passed a validation test, in this case a motor skill validation test 1306. If the patient passes the validation test (yes 1308), the program indicates that an opioid dose 1182 should be dispensed. If the answer is no 1310, the program indicates that no opioid dose 1174 should be dispensed.

Fig. 41 is an exemplary embodiment of using patient self-assessment and self-reporting information to make a dispense 1182 or no-dispense 1174 opioid dose decision. For example, if patient 6 is taking opioids, and if patient 6 is or will be severely constipated, the patient may want to avoid taking more medication. In this case, for example, the combination of the abdominal pain level 1320 of the self-assessed patient and the consistency 1322 of the last stool and the number of bowel movements 1324 of the self-reported patient allows for an informed dispensing 1182 or no dispensing 1174 opioid dosage decision, even though prescription 4 would allow dispensing of the medication prior to talking with a medical professional. In this embodiment, this is before talking to the integrated support center 22. The routine may also be used to remind the patient 6 that he/she may become constipation and should consider taking purgatives or talking to his prescriber 2, etc.

FIG. 42 is an exemplary embodiment of a routine that may make an allocation or non-allocation decision using information from a patient self-assessment and self-report. To make a dispense 1182 or no dispense 1174 opioid dose decision, the program determines whether the pain level is greater than a predetermined level, such as level 2 (1330); if not 1332, then the decision is to not allocate 1174. If the pain level is greater than 21330 (yes 1334), the program determines if the stool composition of the last bowel movement is greater than 3 (1336); if not 1338, then the decision is to not allocate 1174. If the consistency of the last stool was greater than 3(1336), 1340, then the program determines if the patient had one or more bowel movements within the immediately past 48 hours 1342; if not 1334, then the decision is to not allocate 1174. If the answer is 1346, then the decision is to dispense 1182 opioid doses.

Example IV

Embodiments of the invention may be used, among other uses, to 1) improve the safety profile of a drug by ensuring proper, personalized opioid prescription and prescription management (e.g., personalized dispensing), 2) ensure that the drug treatment is effective, 3) as a diagnostic aid/tool, 4) quantify the drug treatment, 5) prevent drug-mediated adverse events, 6) prevent overdosing, 7) prevent underadministration, 8) reduce the likelihood of misuse, 9) reduce the likelihood of abuse, 10) reduce the likelihood of overdosing, 11) improve compliance with the drug prescription, 12) prevent the patient from inadvertently taking repeat doses, 13) reduce the likelihood of addiction, 14) reduce the likelihood of dependence, 15) better manage opioid tolerance, 16) manage drug withdrawal, 17) enable PRN administration, for example, managing "patient-controlled oral analgesia^TM”(PCOA^TM) 18), preventing drug emissions, 19) preventing accidental ingestion of opioids by children, 20) avoiding drug interactions, 21) better managing drug-mediated side effects, 22) promoting prescription persistence, 23) transferring any potential responsibility of the drug manufacturer or opioid prescriber 2 to the patient 6, 24) capturing patient self-assessment, self-testing, self-reporting, and digitally-captured information needed to control drug dispensing and/or meet reporting requirements of clinical trial regulatory bodies, 25) capturing opioid-related side effects to aid better patient management, 26) streamlined opioid risk assessment and mitigation strategy (REMS) reporting, 27) simplifying Prescription Drug Monitoring Plan (PDMPs) record keeping and reporting, and the like. In short, opioid therapy is personalized by improving the drug/safety profile of the opioid.

Ideal opioid management allows physicians to evaluate patients each time before allowing them to take their prescribed opioid dose/drug. Before authorizing a patient to take a dose, a physician determines how effective the current dose manages the patient's pain/symptoms and looks for signs of opioid side effects, addiction, dependence, misuse, abuse, possible adverse drug-drug combinations, and the like. In this way, the physician may alter/improve the dosage for the patient and/or prevent the patient from taking opioids in the event that the physician determines that no dosage is needed and/or that the dosage may result in severe opioid-mediated events and/or undesirable side effects. It is neither practical nor cost-effective for the physician to approve each dose before the patient 6 takes it, and embodiments of the present invention combine many considerations that the physician takes into account before allowing the patient to dispense an opioid dose from the drug dispenser 16.

A. Opioids

Opioids are excellent examples of how embodiments of the present invention can be used to improve opioid and other drug management and patient outcomes.

B. Background of the invention

The following describes some, but not all, of the key opioid side effects as background to the opioid examples of the subsequent embodiments:

cognitive impairmentIt is well known that larger doses of opioids are clearly harmful, leading to drowsiness, lethargy and even death. At least one prospective study showed: patients with chronic pain receiving opioid treatment suffer from cognitive deficits including decreased spatial memory capacity and impaired performance of working memory assessments (Schiltenwolf et al, 2014).

Respiratory depressionOpioids have an adverse effect on the respiratory system. Carbon dioxide (CO) in blood₂) The horizontal stimulates our respiratory drive. As respiration slows, CO₂The level is increased, thereby stimulating the brainstem to increase the respiratory rate.

Low oxygen levels do not stimulate respiration and are therefore selective for CO₂Horizontal sensitivity is an important function of nerve cells in the brain stem. Opioids prevent this feedback loop. When the individual takes A in an excessive amountWith tablets, high levels of opioids reduce alertness and induce sleep. During sleep, it is CO₂The feedback loop allows the person to keep breathing. However, when blocked by high levels of opioids, breathing slows or stops, and overdosing does suffocate.

Heart rateThe heart rate may become fast or very slow. Some opioid users may also experience severe drops in blood pressure or postural hypotension when standing from a sitting or lying position.

This is also problematic for individuals with lung disease or sleep apnea. People with chronic lung disease often require elevated levels of carbon dioxide to stimulate them to breathe deeper. The administration of opioids attenuates this response, resulting in persons with lung disease breathing slower and therefore having low oxygen levels.

Sleep apneaSimilar to people stopping breathing periodically during the night until their carbon dioxide levels are high enough to stimulate their brain to send out a gasp signal. When opioids interfere with this reaction, the result may be life threatening. Opioids have been shown to exacerbate the onset of apnea in sleep apnea patients (Jungquist, Flannery, Perlis,&Grace,2012)。

miosis of the pupilThe use of opioids results in the formation of a small, constricted pupil, similar to the pupil's response to intense light.

ConstipationOpioids cause slow peristaltic movements in the digestive tract. This leads to a stasis or loss of the intestinal contents and to severe constipation, especially in the case of long-term use.

Sleepiness or sedationOpioids (particularly morphine) are known to cause severe sedation and drowsiness.

MyoclonusHigh doses of opioids can lead to muscle stiffness and abnormal movement of the limbs and muscles.

HyperalgesiaAllergy (Miao)Opioid-induced hyperalgesia (OIH) is another side effect of the use of opioids. Opioid hyperalgesia is a phenomenon in which the body's sensitivity to pain secondary to opioid use is increased (allergy-excessive or excessive, pain-sensitivity to pain).

Pain is an important part of our body's defense system, alerting us to current or impending injury or harm. Since opioids reduce our brain's sensitivity to pain signals from other parts of the body, our brain begins to compensate by increasing our recognition and sensitivity to pain. The pain neurons entering the brain actually change, making them more responsive to pain and enhancing our perception of pain. This change is called neuroplasticity of the nerve cells. Many mechanisms are thought to involve these changes (m.lee, Silverman, Hansen, Patel, & machikani, 2011). The result of this change is: after a decrease in opioid levels, our pain fibers are more sensitive than before the opioid, resulting in increased pain.

Unfortunately, pain exacerbation can also mean progression of disease or development of tolerance to current opioid doses. For these cases, the opioid dose is often increased. In contrast, treatment of opioid hyperalgesia is the reduction or cessation of opioids.

Tolerance and withdrawalTolerability occurs when physiological (neuroplastic and chemical) changes occur in the body, leading to a decrease in the effectiveness of the drug, requiring higher doses to achieve the same effect. Withdrawal is an unpleasant symptom that can occur after the drug is reduced or discontinued. Brain changes and measurable withdrawal symptoms can occur following a dose of opioid (Rothwell, Thomas,&Gewirtz,2012)。

in clinical practice, withdrawal symptoms may occur after five to seven days of opioid drug treatment (Anand et al, 2010). Withdrawal symptoms may include myalgia (muscle pain), tremor, sweating, anxiety, increased pain, accelerated heartbeat, mydriasis, yawning, diarrhea, and nausea.

Withdrawal is extremely unpleasant and can be alleviated by taking another opioid dose. Tolerance and withdrawal are not considered as addiction. Tolerance can occur due to physiological changes resulting from exposure to opioids. Withdrawal is the unpleasant physical and emotional symptoms that occur after withdrawal of opioids after tolerance is developed.

Addiction (addiction)Addiction is characterized by an inability to continue continence, impaired control of behavior, cravings, diminished awareness of major problems with human behavior and interpersonal relationships, and emotional reactions to dysfunction.

Death was caused by deathOne factor is not usually considered when prescribing opioid pain medications-the overall increase in mortality. Opioids cause more deaths than any other drug. The medical ethical principles of non-harm (non-harm) now extend outside the diagnostic room: the interaction between the physician and his/her patient may adversely affect the life and health of others who are not part of the medical decision. Damage to opioids may result in workplace safety accidents or unintended death from motor vehicle collisions. The use of opioids may also lead to falls and increased mortality in the elderly.

Benzodiazepines (Benzodiazepines)It is also important to recognize that the risk of death is significantly increased when opioids are taken together with benzodiazepines. The combination of opioids and benzodiazepines is the leading cause of excessive death when multiple drugs are involved (Calcaterra, Glanz,&binswanger, 2013). Despite this risk, about 30% of people receiving chronic opioid therapy are prescribed benzodiazepines (Nowak, Abou-Nader,&Stettin,2014)。

C. opioid prescription

Prescription making tool

The opioid-specific App12 is designed to be customizable for each patient 6. When the prescriber 2 enters a prescription 4, he/she may select from a list that includes all potential opioid side effects and/or any information required by regulatory agencies (e.g., FDA or EMA) for clinical trials and/or drug approval. The prescriber 2 may also select the frequency at which each message is prompted to the patient, e.g., each time before dispensing an opioid, at a specified time interval, when another value occurs above or below or within a specified range of the specified value, etc. These values may include digitally captured or patient entered physiological, psychological, lifestyle, medications taken concurrently since the last opioid dose, and/or environmental information. The captured information may not, or may be used by the opioid specific dispensing algorithm 13 to make a decision to dispense or not dispense a dose.

The values are stored by the opioid specific App12 on an associated interface database 278 file residing on the interface device 14, or on the stand-alone drug dispenser 16, and synchronized with the patient database 152 stored on the data server 10 for future reference. The information is organized for use by the patient 6, the drug specific dispensing algorithm 13, the caregiver, the physician of the patient 6, and/or the prescriber 2 to better manage opioid administration and/or the patient's treatment/therapy, as well as for trend analysis by the analysis program on the data server 10 and/or the opioid specific App12 to help develop optimal therapy.

Creating personalized medication dispensing apps

Once the prescription is entered electronically, submitted 150, the App generation program 200 on the data server 10 creates a personalized patient 6 opioid specific App12 and creates and links together the relevant patient 6 records/databases present on the data server 10. Thereafter, it sends a download link to the patient 6 and a copy to the appropriate personnel, such as the caregiver, prescriber 2, pharmacy 8, etc., for the patient 6 to download the opioid specific App12 to the interface device 14 or to the separate disposable medication dispenser 16. If the patient 6 encounters any problems while downloading the opioid specific App12, the caregiver, prescriber 2 or staff thereof, the integrated support center 22 and/or pharmacy 8 staff may assist the patient 6 in resolving the problem.

Special App of special opioid of individualized patient

After downloading the personalized opioid specific App12, the patient 6 opens the opioid specific App12 and enters the necessary patient 6 information, which enables a biometric login 280 linking the patient 6 to the prescription 4 and the opioid specific App 12.

Filling the cartridges into reusable medicament dispensers

In reusable drug dispensers 16, opening a drug dispenser 16 requires a unique dispenser identification number 158 that is automatically issued by the patient database 152App generation program 200 upon submission 150 of the electronic prescription 4. Opening the reusable medication dispenser 16 to load the restricted medication requires an authorization code. If the dispenser is used for opioids, the authorization code limits the reusable drug dispenser 16 to be opened only by healthcare professionals authorized to handle opioid prescriptions to load a replacement opioid cartridge 18, thereby reducing opioid emissions. A USB cable is required to open the reusable medication dispenser 16. When a USB cable is inserted to power the locking and unlocking of the reusable medication dispenser 16 micro-actuator 1028, an authorization code must be entered to open the reusable medication dispenser 16.

After opening, 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 App12 identifies the reusable drug dispenser 16 and that the reusable drug dispenser 16 is ready to dispense the drug. If a new prescription, the opioid-specific App12 is immediately ready to dispense medication using the authorized biometric authentication 850 and patient 6 response information 862, 864, 866. If a supplement to the existing opioid, the opioid specific App12 dispenses the medication following prescription authorization after biometric authentication 850, entering the necessary information, and checks to ensure that the prescribed 4 opioids have not been previously dispensed using a different medication dispenser 16. This eliminates repeated dosing of authorized opioid doses.

If for any reason the opioid specific App12 does not identify the drug dispenser 16 or the drug is not a designated opioid, the opioid specific App12 will display a reminder and display the problem so that it can be resolved. Clicking on the reminder screen on interface device 14 connects the individual with integrated support center 22. For a stand-alone medication dispenser 16 without telephony functionality, the notification shows the number to be called for support.

When the opioid-specific App12 identifies the reusable drug dispenser 16 and the opioid in the cartridge 18 as a supplement to the prescribed drug, the opioid-specific App12 checks whether the drug in the first cartridge is fully dispensed. If not, the medical professional loading the cartridge 18 is notified: 1) a second cartridge 18 that is not allowed to begin dispensing medication for the same medication until the dose in the first cartridge 18 has been fully dispensed, or 2) the ability to dispense from the first or previous cartridge 18 will be prevented and the medical professional should discard the first cartridge 18. Replacement cartridges 18 are recorded in the central server 10 before the cartridges 18 are completely consumed in accordance with the authorized prescription 4 to help track potential opioid emanations. The notification also provides the necessary troubleshooting/reset indication that is intended to ensure that a given patient cannot dispense more opioid than prescription 4 allows, within a prescribed period of time, regardless of the number of drug dispensers 16 that patient 6 may have containing the prescription medication.

When ready, a screen ready for dispensing appears. Then, if the cartridge 18 is loaded by a medical professional, the individual will provide the patient 6 with a closed, loaded and locked tamper-resistant drug dispenser 16 containing the prescription opioid in the cartridge 18 along with associated package insert, prescription, and patient instructions, substantially identical to any other prescription.

Dispenser for dispensing a disposable medicament

In the case of the disposable medication dispenser 16, dispensing only requires the pharmacy 8 to dispense the opioid, much the same as any other prepackaged medication. The opioid-specific App12 will enable signal exchange with the disposable drug dispenser 16 and automatically prevent dual dispensing of the same prescribed opioid dose from more than one drug dispenser 16 at the same time. The opioid specific App12 ensures that all dispensing is restricted as prescribed 4.

Once identified by the opioid specific App12, App12 records the unique serial number of the drug dispenser 16, the unique serial number of the drug cassette 18, the NDC number of the drug, the opioid lot number, the opioid expiration date 458 and the prescription expiration date 103 (expiration date), as well as unique storage parameters 460, 462, etc. Thereafter, the opioid-specific App12 does not dispense prescribed opioids, such as oxycodone, from a different authorized drug dispenser 16. Repeated dosing is not allowed to occur.

Closed loop tracking

The integrated system enables closed loop tracking of opioids, including the prescriber 2, the prescription 4, the patient 6, the pharmacy 8, the data server 10, the opioid specific App12, the interface device 14, the medication dispenser 16, the medication box 18, and if applicable, the RFID pill 20, and/or a self-taken picture 21 capturing that the patient 6 is taking the pill. The opioid may be tracked from the time the kit 18 is filled with the opioid to the time the opioid is dispensed or ingested.

Patient value

Ensuring proper opioid use (e.g.) As how this embodiment is used to ensure drug efficacy, proper opioid use and avoidance of drug-mediated adverse events, overdose, abuse, misuse, underadministration, overdoseExamples of drug-drug interactions, addiction, dependence, and adverse. It can be used for drug quantification, withdrawal, prevention of side effects (e.g. opioid-induced constipation), and better patient management by capturing certain drug-related side effects. This information may also be used to capture Patient Report Outcome (PRO) information required by regulatory body submissions during clinical trials.

The captured information is dependent on the medication and/or medication specific dispensing algorithm 13. For example, the CDC recommends that physicians periodically assess pain using a validated tool, such as a 3-item (PEG) assessment scale, which may be incorporated by embodiments of the present invention, to report to the appropriate healthcare professional obtaining approval for patient 6:

1. which number best describes your average pain in the last week? (from 0 no pain to 10 the most severe pain you can imagine)

2. Which figure best describes how does the pain interfere with your enjoyment of life during the past week? (from 0 to no interference 10 to complete interference)

3. Which figure best describes how the pain was disturbing your general activity during the past week? (from 0 to no interference 10 to complete interference).

Examples of values that may be tracked by the opioid specific App12 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) oxygen saturation due to slow and/or shallow breathing (SpO) caused by opioids₂) A decrease, (ii) a fast or very slow heart rate, (iii) cognitive impairment, (iv) an ambiguous and/or altered speech pattern, (v) a miosis, and/or (vi) weight loss. A good example of an avoidable side effect is constipation.

One common approach to non-invasive pulse oximetry that may be incorporated into interface device 14 uses a dual wavelength sensor placed across a length of venous tissue, such as a patient's finger (placed over the sensor), to measureThe percentage of oxyhemoglobin in arterial blood is measured, thereby measuring the oxygen saturation of the patient. In addition, since oxyhemoglobin at a particular tissue location is pulsatile in nature and synchronized with the entire circulatory system, the system indirectly measures the pulse rate of the patient. Low SpO₂Indicating hypoxemia, which may be caused by very slow and shallow breathing due to excess opioid.

For detecting and administering narcotic analgesics (e.g.Oxycodone, hydromorphone, hydrocodone, morphine, etc.), systems that indicate the respiratory and cardiac status of a patient without the need to invasively measure or sample the patient's blood are particularly desirable and useful. Today, they are available as apps on smartphones and real-time fitness monitoring devices (e.g., FitBit, Jawbone, and Fuelband, etc.). For example, (i) non-invasive pulse oximetry for monitoring blood oxygen saturation, and (ii) pulse rates are now readily available on smartphones (e.g., Galaxy 6S and 7S, samsung, with S Health App with pulse, heart and oxygen saturation monitors, similar App to iPhone for Apple, iOximeter, etc.) and wearable diagnostic and/or monitoring devices. This embodiment has the ability to import, for example, oxygen saturation and heart rate values from these devices through the development of APIs (application program interfaces).

Thus, SpO₂May be measured as a self-test 84 on the interface device 14 and/or by digital capture from another App 852, 858, 859, 860 and/or digital capture values from the oximetry device 882.

The heart rate may be digitally captured on an ongoing basis by a digital monitor 859 and/or as a self-test 864.

Impaired cognition can be indicated by manual dexterity reflex self-detection 864. The results are then compared to the base and trend values to determine the cognitive changes of the patient 6.

The change in speech pattern can be recognized using ambiguity (skewing) and volume self-detection 864. The results are then compared to the base and trend values to determine changes in the voice and volume of the patient 6. The integrated support center 22 may utilize IBM Watson tone detection to listen when the patient 6 calls as input to decide whether to allow the patient 6 to dispense an opioid dose that has been prohibited by the opioid specific dispensing algorithm. The integrated support center 22 may utilize two-way video conferencing to utilize IBM Watson's facial recognition software to compare the patient's 6 face to the metadata face comparison study to determine if the patient 6 is likely to be overdose or marginally (borderline) to guide any call center decisions, etc.

The pupillary constriction self-detection 864 can be performed by having the patient 6 photograph his/her eyes or face. The results are then submitted to an appropriate light adjustment algorithm, and the pupillary constriction measurements are then compared to the base and trend values to determine the change in pupillary constriction of the patient 6, and thus to determine whether over-constriction of the pupil has occurred, which may be the result of opioid overdosing. Iris scan biometric recognition may be used to automatically capture pupil scans.

The weight loss can be tracked using the digital scale 858 via digital capture via an API from a digital interface 860 and/or via a self-report 866.

Utilizing a self-report 866 on stool consistency (e.g., using Bristol stool index) and stool frequency may indicate when a patient is likely to tend toward opioid-induced constipation and enable prophylactic use of a prescription laxative.

Tracking certain drug-related side effects through self-assessment 862, self-detection 864, and/or self-reporting 868 may help prescribers 2 manage certain patients 6.

Digital or self-reported tracking of the medication taken by patient 6 since patient 6 took its last opioid dose may reduce the likelihood of drug-drug adverse events, overdosing.

A number of factors can interfere with how a drug is metabolized and change the need for or effectiveness of the drug over time. Continuous monitoring while patient 6 is taking opioids enables tracking trends to ensure that the opioid is continuously effective to the patient, and to monitor and manage any changes in patient drug tolerance, etc.

Dispensing

If information capture is not performable, then information capture has little value. The medication specific dispensing algorithm 13 is designed to incorporate certain medication specific values to make a dispense or no-dispense decision, even if the dispense is otherwise authorized by the prescription. This enables the personalization of each drug prescription 4 for an individual patient 6, thereby significantly improving the efficacy/safety profile of the drug.

In this embodiment, the patient will be prescribed opioids, among: (i) a disposable drug dispenser 16 containing a specified opioid, or (ii) a cartridge 18, to be loaded into the reusable drug dispenser 16 by a healthcare professional and dispensed to the patient 6 using the reusable drug dispenser 16 with the cartridge 18 docked into a tamper-resistant unit controlled by the opioid-specific App 12. When the patient 6 clicks on the opioid specific App12 to take his/her next dose, the drug specific dispensing algorithm 13 will automatically check to ensure that the drug is not expired 542, if it is not, whether the opioid is stored within the opioid specific temperature 558 and humidity range 566, if the drug is already properly stored, it will check the prescription 4 to determine when the patient 6 can take his/her next dose 580, 584, 588, after which it will signal with the designated equipment to digitally capture, for example, the patient's 6 heart rate (to see if it is slow and unstable), weight information (to see if the patient 6 is losing weight), etc. Thereafter, it queries the patient 6 for at least one patient self-assessment 862, patient self-test 864, and/or patient self-report 866 question by calling up the corresponding screen. One example of a patient self-assessment 862 screen is the pain level of patient 6 using the Wong-Baker facts scale. An example of a self-test 864 screen mayThe method comprises the following steps: (i) motor skill detection to determine cognition, (ii) self-managed peripheral capillary oxygen saturation (SpO)₂) Detection 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) patient 6 takes a self-photograph of his/her eyes or face (with his/her eyes open) to determine whether his/her pupils are over-constricted, which may be due to opioid overdosing, (iv) voiceprint to determine whether patient 6 is slurred, changes in the patient's speaking rate, and/or changes in normal volume, etc. Examples of patient self-reports 866 include, but are not limited to: (i) stool composition using a scale such as the Bristol stool scale to determine whether a patient is likely to develop constipation (likely opioid-induced constipation), (ii) stool frequency screening to determine any stool changes that may indicate constipation, (iii) queries for new or altered use of drugs that may interact with opioids, and the like.

The medication-specific allocation algorithm 13 may use any combination of digitally captured 852, 854, 856, 857, 858, 859, 860, 880, 882, 884, 886, self-assessment 862, self-detection 864, self-reporting 866, physiological, psychological, lifestyle, other medication taken and environmental data to make an allocation 868 or no allocation 870, 872, 874 decision. The data capture may be the same each time the patient 6 wants to dispense a dose, or (i) the data request may be triggered by a series of information where a value within a particular range (e.g., heart rate) may contribute to a particular input (e.g., SpO)₂Self-test 864), or (ii) if a value on another screen falls within a predetermined range or if the patient 6 answers a particular question in some manner, etc., a data screen may be presented on the interface device 14 at predetermined intervals (e.g., at intervals of a predefined time interval, at intervals of multiple assignments).

For example, after biometric authentication 850, the drug-specific dispensing algorithm 13 of the opioid-specific App12 uses a decision tree, see fig. 11-16. The algorithm can be very simple: biometric enrollment using iris scanning, followed by photomodulationAnd trending iris scan data to measure and compare pupil size to baseline values to determine whether patient 6 has an eye pupil over constriction, which may be an indication of opioid overdose or overdose if another dose is taken. If the iris scan is within an acceptable range, the algorithm may: (i) show Wong BakerGauge to track the patient 6 for pain over time (or skip this step), and/or (ii) go to the ready to dispense 868 screen-allowing the patient 6 to dispense a dose by clicking on the dispense button of the medication dispenser 16.

Alternatively, it may use, for example, a fingerprint scan. After authentication, the algorithm may proceed by using Wong Baker on the first self-assessment 862 screenThe patient 6 is asked to click on his/her pain level to start capturing the patient 6 input data. The pain level information is used to track the efficacy of the opioid and provide trend data to determine whether patient 6 is developing opioid tolerance. After clicking on the corresponding value, the algorithm automatically exhibits, for example, SpO₂Self-test 864 screen. SpO₂After self-test 864 was completed, drug-specific dispensing App 13 evaluated trending SpO₂Data to determine whether the patient 6 is hypoxic or likely to tend to be hypoxic. If potential respiratory depression is suspected, a cognitive self-test 864 is automatically presented that would not otherwise be presented. If everything is within the acceptable range, the medication-specific dispensing algorithm 13 may present, for example, a constipation self-report 866 screen, may query the CDC recommended 3-item PEG assessment scale, query the prescriber 2 for requested side-effect information, and/or clinical trial PRO data, or directly enter a ready-to-dispense 868 screen. At this point, the patient 6 need only click on the dispense button of the medication dispenser 16 to dispense a dose.

However, if based on SpO₂And cognitive trend data, algorithmsSuspected opioid toxicity (excess), it may require additional confirmatory information, such as conversational self-test 864, miosis self-photograph, etc. Once the medication specific dispensing algorithm 13 confirms that a potentially toxic event exists or may occur, it locks the medication dispenser 16 and generates a corresponding screen 874 telling the patient to contact the integrated support center 22, or talk to their prescriber 2 or physician before the next dose can be dispensed, etc., even if the dose is within the prescribed parameters.

After talking to the patient 6, the integrated support center 22 representative may decide within its operational constraints whether to remotely unlock the medication dispenser 16 and allow the patient 6 to dispense the opioid. If it appears inappropriate to authorize patient 6 to dispense opioids, the representative may assign patient 6 to an integrated support center 22 physician or other medical professional. If authorized, the physician may change the prescription 4 and may decide whether to unlock the medication dispenser 16 and allow the patient 6 to dispense medication. Anyone who last contacts patient 6 is responsible for: (i) terminating the phone call with the patient 6, (ii) sending a summarized email containing an indication 830 to the patient 6, (iii) updating the patient's record 818, (iv) notifying the prescriber 2 that the assignment has stopped or the prescription 4 changed 832, and (v) updating the electronic medical record 24.

If the prescriber 2 has advice, the prescription may be changed based on the prescriber's 2 instructions by a standalone medication dispenser 16 or an integrated support center 22 in the patient's 6 opioid specific App12 present on the patient's 6 interface device 14.

This embodiment personalizes opioid therapy, improves the drug/safety profile of drug therapy, and improves the quality of life of patient 6, while reducing preventable side effects, accidents, and overdoses, thereby reducing the number of physician interactions and ER visits-saving overall costs for patient care and life saving.

D. Drug recall or clinical trial drug discontinuation

In the case of a drug recall or in the case of a drug in clinical trial, the integrated support center 22, within its program and control, can remotely lock all drug dispensers 16 containing a given opioid and simultaneously notify the patient 6 that he/she is unable to dispense the opioid and how they should do.

E. Quantification of

Embodiments of the present invention may also be used to assist in opioid quantitation. Quantification helps the body adapt to drug treatment and generally reduces the common side effects that can occur when opioid therapy is initiated. The doctor/prescriber 6 may start with an initial low dose of opioid and carefully adjust the dose up to the appropriate level. Quantification helps to find the optimal dose to improve daily function. For example, the opioid dose is slowly increased to the highest tolerated dose. Once the symptoms do not improve further with increasing doses, prescriber 6 reduces the dose to the previous one. If a higher dose produces too many side effects, the dose is reduced. Opioid management is based on the individual's own personal needs and responses. The optimal dose of opioid is a dose that significantly improves daily function and minimizes side effects.

Pain management has three simple goals:

(i) the sleep at night is good, and the sleep is good,

(ii) pain control at rest during the day,

(iii) pain control of the patient 6 during mobility and ambulation.

If there is no past history of opioid intake, the starting dose is calculated by assessing the severity of pain, the age, weight, sex and general physical condition of the patient.

The invention is designed to enable the control of analgesia using oral patients and for example Wong BakerA combination of 0 to 10 pain self-assessment indices to alter how opioids are quantified. The modified therapy enables the patient 6 toLow doses of opioid were administered as needed for some of the waiting time between doses. Once the self-assessed pain index level reaches a certain level of pain control, the interval between doses is extended until the level of pain begins to increase again. At this point, the interval between doses may be shortened back to the previous interval. Examination of the data allows the prescriber 2 to increase the intensity of the prescribed dose, to reduce the number of doses that the patient 6 must take to control his/her pain, etc.

Pain assessment

Assessment and re-assessment of pain following administration of analgesics or pain management is conducted in the healthcare facility by a regulatory agency such as a joint committee. The joint council began to set pain assessment criteria in 2001, indicating that the route of analgesic administration determines the time for pain re-assessment, as different routes require different times for the drug to have a therapeutic effect. Oral Immediate Release (IR) drugs take 45-69 minutes.

Most pain assessments are made in the form of a scale. The scale is interpreted to patient 6, and the patient then selects a pain score. Ratings were made before any drug was administered and after the specified time frame to assess the effect of treatment. The patient rated pain on a scale from 0-10, with 0 indicating no pain and 10 indicating the most severe pain that could be imagined. Patient 6 is presented with a scale with a corresponding face volume, such as Wong Baker facts, which describe various pain levels, one of which is selected by the patient. Patients who are unable to speak/understand pain scales are evaluated using different types of scales.

Embodiments of the present invention allow pain assessment over a period of time under real-life conditions. This may allow a better assessment of the pain level of the patient 6 and enable a better pain management.

Opioid quantitation

The prescription 4 may be written to allow the patient 6 to gradually increase his 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. For example, patient 6 may be administered every so many hours and/or portions thereof, or patient 6 may be administered more frequently throughout the day, e.g., from b.i.d. to t.i.d., from t.i.d. to q.i.d., from q.i.d. to every two hours, from every two hours to q.h. The data can also be based on trending patient self-assessment 862 and self-reported associated reduction in 866 opioid-induced side effects indicates that repeat dosing before sleep is allowed and dosing as needed at the point where pain is controlled.

Once steady state is reached, prescriber 2 may change the prescription to optimally manage the pain of patient 6.

Dosing may be facilitated by using a particular dosing cartridge 18, 18a, 18b, 900 configuration containing more than one opioid intensity.

F. Patient-controlled oral analgesia (PCOA)^TM)

The features of this embodiment enable patient-controlled oral analgesia (PCOA)^TM) It becomes possible, even for drugs that are not approved for PRN administration (e.g. for example) As well as so. The study showed that: patients who may be self-treated as approved (e.g., with PRN set prescription parameters) tend to use less drug, thereby further mitigating potential side effects.

While it is generally recommended that analgesic drugs for moderate to severe pain be administered on a regular basis, the use of this embodiment allows for PCOA^TMAnd (4) administration. The patient 6 may be allowed to dispense a number of pills during a defined period of time, not exceeding a specified amount. A minimum interval between doses may also be set. This can be further limited to a total allowable dose limited to a few hours or during a given 24 hour period, limited to a dose limit.

PCOA^TMPrescription is allowed to manage breakthrough pain while controlling the maximum allowable dose. PCOA^TMAllowing immediate release opioids to be used with extended release opioids to address the problem of breakthrough pain. Rather, it also allows for elimination of the time-release opioid, thereby allowing the dosing schedule to be consistent with the pain of patient 6.

G. Diagnosis of

Embodiments of the present invention may also be used to assist in diagnosis. For example, there are many different types of pain and different types of headache. Patients are usually first self-treated with an over-the-counter (OTC) analgesic, such as aspirin. As pain or discomfort increases, patients increase the number of tablets (i.e., the dose) taken, as well as the frequency of self-medication. At some point they go to their physician seeking appropriate relief.

When the doctor is talking to the patient 6, he/she can describe many different types of pain, making diagnosis difficult. Pain has a variety of causes and people respond to it in a variety of unique ways. The pain that one person can tolerate may not be suitable for other people.

Headache represents one example. It is important to figure out the type of headache that causes pain. If the doctor knows the type of headache he/she can treat properly. However, as highlighted by a study in 2004, 80% of people with recently self-described or physician-diagnosed sinus headache but no evidence of sinus infection actually met the criteria for migraine. Different types of headaches are discussed below:

1) tension headaches, the most common type of headache, can be suitably treated, usually by over-the-counter treatment such as aspirin, ibuprofen or acetaminophen (Tylenol). Experts believe that these may be caused by contractions of the neck and scalp muscles (including responses to pressure) and possibly changes in brain chemistry.

2) Cluster headaches, which affect more men than women, are recurrent headaches that occur in groups or periodically. They appear suddenly and are characterized by: severe, debilitating pain on one side of the head, and usually with a waning eye and nasal or runny nose on the same side of the face. During an attack, people often feel anxious and uncomfortable; they are unlikely to lie down as a person with migraine would do. The cause of cluster headache is not clear, but genetic factors may be present. There is no cure, but the drug can decrease the frequency and duration.

3) Sinus headaches can occur when the sinuses are inflamed, usually due to infection. They can generally be diagnosed by the presence or symptoms of pus observed by fiber optic mirrors. Headache caused by sinus infections can be treated with antibiotics as well as antihistamines or decongestants.

4) Ironically, rebound headaches can be caused by the excessive use of analgesics to treat the headache. The chief culprits include over-the-counter drugs such as aspirin, acetaminophen (Tylenol) or ibuprofen (Motrin, Advil), and prescription drugs.

5) Migraine can be familial inherited, diagnosed using certain criteria: (i) at least 5 pre-headache pain, (ii) lasting 4-72 hours, (iii) at least two of the four headache pain's have unilateral pain, throbbing pain, moderate to severe pain, pain interfering with daily activities, pain worsening with daily activities, or pain preventing daily activities, and (iv) at least one of the following is associated with pain: nausea and/or vomiting, or, if those are not present, sensitivity to light and sound. Auras such as visual distortion or hand numbness may be indicative of migraine. (about 15% to 20% of migraine sufferers experience these.)

6) Mixed headache syndrome, also known as migraine headache, is a combination of migraine and tension headache.

7) Acute headache is a headache that occurs suddenly and has symptoms that resolve after a relatively short period of time.

8) Hormonal headaches are commonly associated with changes in the levels of hormones in women during menstruation, pregnancy and menopause. Chemically induced hormonal changes (e.g. using contraceptives) can also cause headaches in some women.

9) Chronic progressive headache, also known as traction or inflammatory headache, is a chronic progressive headache that becomes heavier and occurs more often over time. These are the least common headache types, accounting for less than 5% of all adult headaches and less than 2% of all children's headaches. Chronic progressive headache can be the result of disease or disorder of the brain or skull.

Diagnosis requires headache assessment, which includes: (i) history of headache, (ii) description of headache, (iii) symptoms of headache, (iv) characteristics, (v) list of events that caused headache, (vi) list of events that aggravated headache, and (vii) what the patient did to relieve headache. The patient is also asked to keep a log of headaches.

The appropriate treatment depends on several factors, including the type and frequency of headache and its cause. There are a number of migraine and headache medications and other treatments available. Appropriate treatment will generally depend on the type of headache.

Headache pain may require management with medication. Headache medications for treating headache can be divided into three different categories: relief of symptoms (drugs for treating headache or symptoms accompanying migraine such as nausea), abortive therapy (drugs for stopping migraine) and prophylactic therapy (drugs for preventing migraine). Botulinum injections represent another treatment for migraine and headache.

The way the body responds to migraine and headache medications may change over time, and thus the medications may need to be adjusted.

Embodiments of the present invention enable a compilation of patient 6-specific assignment information and patient self-assessment 862 and/or self-report 866 information to be specifically developed to aid in diagnosing and managing headaches.

H. Management of complex drug therapies

This embodiment includes the use of multi-drug dispensers 1002, 1004, 1006, 1008 in combination with a combination therapy App 1000, which allows for the dispensing and control of two or more drugs to better manage complex drug therapies. For example, to dispense a long-acting opioid, an immediate release opioid, and one or more drugs to address the side effects caused by the opioid (when certain self-assessments 862, self-tests 864, self-reports 866, or digitally captured information indicate symptoms, a drug is needed to treat side effects (e.g., diarrhea and vomiting)).

I. Opioid problem

Opioids (examples include codeine, fentanyl and analogs, hydrocodone, hydromorphone, methadone, oxycodone, oxymorphone, etc.) are effective in controlling pain. However, physicians are reluctant to prescribe opioids due to their overdose, abuse, addiction and possibility of emission and the associated REMS program. Some patients are also reluctant to take opioids because of their addictive potential. This embodiment provides control and real-time monitoring, addressing the disadvantages of opioids.

Overdose is solved by: 1) a diagnostic screening diagnostic that prevents dispensing of an opioid dose in the following cases: there is an indication that the patient 6 is overdose or may be overdose if the patient 6 takes another opioid dose, even if the dose is authorized by the prescription, and (ii) the patient cannot dispense the dose more frequently than the prescription 4 allows. This is handled by the medicament specific dispensing algorithm 13 which controls the dispensing of the medicament dispenser 16.

Abuse is addressed by the design of the tamper resistant medicament dispenser 16. With respect to the reusable drug dispenser 16, only authorized medical professionals may interface the drug specific cartridges 18 with the reusable drug dispenser 16. Any attempt by an unauthorized person to open the drug dispenser 16 triggers a signal to the opioid specific App12, which the opioid specific App12 automatically locks the drug dispenser 16 and notifies the integrated support center 22. A notification may also be generated if the patient 6 attempts to double the dose using the multiple medication dispenser 16. When the integrated support center 22 is notified, it calls the patient 6 to determine the reason for his/her attempt to turn on the medication dispenser 16 and/or attempt to dispense a repeat dose. At this point, the integrated support center 22 works with the patient 6 to address any dispensing-related issues and may unlock the drug dispenser 16 so that a dose may be dispensed, or if an attempt to abuse is suspected, contact the prescriber 2 to remind them to talk to the patient 6 and ask the prescriber 2 whether the drug dispenser 16 should remain locked so that no opioid can be dispensed or unlocked to allow dispensing. If authorized, the integrated support center 22 updates the electronic medical records 24 associated with the call to the patient 6 and the prescriber 2.

Is reduced byAddiction (addiction)Possibility: (i) the patient is unable to take the medication more frequently than the prescribed medication schedule, regardless of the number of opioid-containing medication dispensers 16 that the patient 6 has, (ii) tracking attempts earlier than the prescribed medication event to enable early intervention, (iii) capturing any attempts to open the medication dispensers 16, and (iv) using time-trending patient self-assessments 862, self-tests 864, self-reports 866, and/or digitally captured relevant information 852, 854, 856, 857, 858, 859, 860, 880, 882, 884, 886 to determine the effectiveness of the opioid in controlling pain in the patient 6. The centralized drug-specific patient and group focused analysis program on the data server 10 is designed to use data analysis on individual and metadata from all patients 6 (data captured by the opioid-specific App 12) to identify potential trends of the patients 6 towards addiction. When a potential addiction is identified, the analysis software alerts the integrated support center 22 so that the integrated support center 22 can alert the prescriber 2 and update the patient's electronic medical record 24. The more data collected and analyzed, the more accurate the predictive analysis.

Is reduced byEmanation: 1) tamper-resistant drug dispenser 16 design that triggers an alarm if an unauthorized attempt to open drug dispenser 16 is sensed, 2) restricts access of drug cassette 18 to the accessible by an authorized medical professionalAmong the reusable drug dispensers 16, 3) limit access to the opioid except for dispensing a single dispensed dose according to the prescription 4 of the patient 6, 4) prevent the dose from being dispensed into a single dose regardless of the number of drug dispensers 16 the patient may have, 5) an automatic closed loop opioid tracking system that: (i) associating a serial number and a drug lot number of the drug-specific cartridge 18 with the drug dispenser 16, (ii) linking the serial number of the drug dispenser 16 to the opioid-specific App12 of the patient 6, (iii) limiting use of the opioid-specific App12 to the particular patient 6, and (iv) the opioid-specific App12 requires a biometric login 850 to access the opioid-specific App12 to instruct the drug dispenser 16 to dispense the opioid. Further, if the medication to be taken can be tracked with the RFID 856 tracking until ingestion and/or filming of the self-photograph 857 confirms that the opioid dose is actually taken by the patient 6, additional control is provided. The time interval between the time of dispensing the medication and the time of ingestion over time provides an indication of compliance, dose reserve or emanation. When combined with metadata analysis by the data server 10, the probability of accurately identifying a potential abuser and an emanation is significantly increased.

Side effectsThe system can also be used to predict potential side effects. For example, opioid-related constipation can be predicted based on self-reports 866 of stool frequency since the last dose or over a particular period of time before, stool consistency of the last stool, and the like. If constipation is predicted, the opioid specific App12 may prompt the patient 6 to take purgatives at the appropriate time. If multiple-drug dispensers 1002, 1004, 1006, 1008 are used, the combination therapy App 1000 may dispense laxatives as well as opioids and/or other drugs as prescribed.

REMSThe system is designed to conform to the respective REMS procedure and virtually eliminates the required data capture and automates patient-specific tracking and assignment report preparation. Integrated support center 22 also supports prescriber 2 by preparing the required REMS reports for all patients including prescriber 2.

Prescription drug monitoring programThe system also allows for the loop between pharmacy 8, prescriber 2 and patient 6 to be closed by controlling and tracking usage on an individual patient 6 and prescriber 4 and dispensing pharmacy 8 basis to redefine the prescribed medication monitoring program.

J. Addiction and withdrawal treatment

Addiction is a global crisis. For example, it is estimated that 240 million opioid dependents exist in the United states, 130 million opioid dependents exist in Europe, and 2 million opioid dependents exist in other parts of the world. Opioid overdose is the second leading cause of unexpected death in the united states. As stated by CDC, overdosing of prescribed opioids took 18000 lives in the united states alone.

Opioid addiction may be treated with buprenorphine and/or naloxone (examples of trade names include bunrans, Suboxone, Zubsolv). In the case of physical dependence, withdrawal must be managed by gradually reducing the drug-dependent opioid dose.

Appropriate precautions must be taken to minimize the risk of misuse, abuse, or diversion, to provide appropriate anti-theft protection, and to minimize the risk of inadvertent child exposure. Furthermore, proper clinical monitoring of the stability of the patient 6 is crucial. Embodiments of the system provide for dispensing control and real-time monitoring, thereby addressing each of these shortcomings.

Dose reduction for the management of addiction and withdrawal takes advantage of all features of the embodiments and is controlled by prescription 4.

K. Clinical trial

The system is designed to capture, store, analyze, and react based on: the medication-specific patient self-assessment 862, self-test 864, self-report 866, and digitally captured 850, 852, 854, 856, 857, 858, 859, 860, 880, 882, 884, 886 physiological, psychological, lifestyle, other medication currently being taken, and environmental information along with the prescription 4 and medication dispensing of the medication and the stored history of the medication dispenser 16 for the opioid-specific App12 to decide whether the medication should be dispensed. The opioid-specific App12 may block dispensing based on established clinical trial guidelines and prescription 4. In this way, patient monitoring information may be utilized to prevent dispensing of the prescribed dose if a potential adverse event is identified.

Most of the time, clinical results are considered to be the final results in clinical trials, as they generally provide a more objective interpretation, higher reliability and a greater degree of simplicity of interpretation. However, certain disease conditions require subjective results to be considered. Regulatory agencies such as the FDA combine Patient Reported Outcomes (PRO) with clinical outcomes in their approval decisions. Examples include: (i) "industrial guidelines, Irritable Bowel Syndrome" -Clinical Evaluation of drugs for Treatment (guidelines for Industry, Irritable Bowel Syndrome-Clinical Evaluation of drugs for Treatment "of FDA at date 5 months 2012, and (ii)" guidelines for drug Evaluation for Treatment of Irritable Bowel Syndrome "of european drug administration (EMA) at date 2015 4 months. They used a combination of PRO and patient self-assessment reports to measure the primary and secondary endpoints required for regulatory approval of any 5HT3 drug for Irritable Bowel Syndrome (IBS).

Interest in developing and applying patient reported results (PRO) is growing among sponsors, clinicians, payers, regulatory bodies, and patients, ranging from drug development to post-market applications. More and more clinical trials are now going beyond the conventional randomized controlled measurements to collect patient self-reported results, focusing on improving patient involvement by introducing patient insights throughout drug development. Analysis of sponsor sponsored interventional studies listed in the clinical trial inventory service of centrwatch found: between 2005 and 2007, only 6.1% of the total study procedures involved some type of subjective outcome assessment. During 2008 to 2010, this ratio increased to 11.8%; recently, this ratio increased to 16.3% of the total study procedure during the years 2011 to 2013. PRO can capture a range of information, from symptom changes and functional levels, to health-related quality of life and treatment satisfaction and compliance.

Although their value is widely recognized, PRO use is often inconsistent and underutilized in understanding patients' perception of their disease (e.g., cancer, cardiovascular disease, diabetes, etc.). Typically, regulatory agencies do not require sponsors to consider PRO in clinical trials until recently much work has not been done to encourage their use. However, evidence suggests that the view is changing. The main medical doctor Janet Woodcock at the FDA's center for drug assessment and research (CDER) represents: "as far as symptoms and impact on quality of life, and what may be an acceptable trade-off in terms of risk and uncertainty, we understand that a chronic patient is an expert in the disease. The FDA faces the challenge of introducing this knowledge in a way that accurately informs regulatory decisions. She asks, "how can we meaningfully collect this knowledge in a rigorous manner given a series of opinions and a series of disease burdens for any given disease? ". PRO measurements are commonly used to evaluate products for the treatment of chronic, disabling diseases, with the therapeutic goal focusing on reducing the frequency, severity, or duration of the disease symptoms.

PRO is often used as a primary endpoint in clinical trials for indications such as migraine and irritable bowel syndrome, where specific symptoms (e.g., pain) play a major role in treatment. PRO is also important in end product labeling where manufacturers can use it to market their products and clinicians can seek information to support their prescription options. Currently, trials for psychiatric and age-related disorders, etc., include PRO as part of the protocol design.

Pain studies initially used PRO as the primary result of clinical trials because attempts to obtain objective pain measurements by pain testers (spring-loaded instruments with gauges for measuring sensitivity to pain or pain level) or by galvanic skin response were less effective than simple pain scales. Other examples of diseases in which PRO is preferred include neurology, depression, anxiety, and Irritable Bowel Syndrome (IBS), which may utilize co-primary and/or key secondary PRO.

The participation of the participants in the retention trial is also a feature of the release and promotion of the PRO guidelines of the FDA at the end of 2009. In 2011, the FDA pursued the next step to seek ways to have a patient have a clear floor in clinical studies by ensuring that all measurements and results reflect the patient's situation through instrumentation or tools and PRO. We are increasingly seeing that patients in clinical trials require knowledge of what is happening, and they wish to have a larger floor.

In general, larger clinical sites may more easily handle adding PRO, while smaller sites, especially in more remote locations, may be more challenging in this regard. Collecting data directly from the patient may provide more powerful information. For example, if a patient is asked to take a medication in some way and does not do so, the patient may be hesitant to report the results.

Furthermore, in some cases, collecting data through a particular data stream provides better quality. Patients will contact an independent group, such as a clinical trial CRO or the integrated support center 22 in an embodiment, and not necessarily need to return to the physician seeking them due to technical issues and concerns.

While in many clinical trials the use of PRO is becoming critical to prove safety and effectiveness for FDA approval, the next step for biopharmaceutical companies and payers will be to combine PRO with other observational studies to create Real World Evidence (RWE). According to the real world data working group of the international society for the study of drug economics, RWEs are becoming critical to sound medical insurance, payment and reimbursement decisions. According to the working group, RWEs can be used with randomized clinical trials to design more effective trials, understand benefit-risk characteristics of drugs, and understand the market for marketing programs. The RWE shows how the medication was accepted by the experienced patient 6. It reveals how drugs are used in different areas and can be used to help make policy or regulatory decisions. It is an extremely reliable source of information.

The embodiment provides: (i) required data capture, (ii) patient 6 participation, (iii) dispensing control, (iv) avoiding certain medication-related side effects, (v) reminding patient 6 in real time to take medication, (vi) providing an intervention reminder if patient 6 fails to take their medication within a predetermined time interval, (viii) dispensing tracking (date and time), (viii) providing an ingestion time if an RFID chip is integrated, (ix) providing ingestion confirmation if a self-photograph is taken, (x) real-time monitoring, and (xi) reporting. It addresses the shortcomings of current systems, capturing and compiling patient 6 and drug specific data in real time to facilitate ongoing clinical trial data summarization, analysis and reporting, while minimizing the number of calls to the clinical trial physician.

In the current embodiment, the patient 6 will be prescribed an opioid to be dispensed in accordance with the determined prescription using a drug dispenser 16 controlled by the opioid specific App 12. When the patient 6 clicks on the opioid specific App12 to take his/her next dose, the drug specific dispensing algorithm 13 automatically signals the drug dispenser 16, signals the determined digital device (e.g., blood pressure, heart rate, etc.) (see fig. 18, 19), and downloads the latest data to the opioid specific App12 database of the interface device 14, checks to ensure that the drug is not expired 458, and if the drug is not expired, checks to see if it has been properly stored 460, 462. If the medication has been properly stored, for example, it will automatically move to the next screen and ask the patient 6 to answer a particular question. In this example, the patient 6 will answer the FDA and EMA required PRO and data capture screens 862, 864, 866 for approval of opioid and supplemental requirements. The ability to capture the requisite PRO primary and secondary endpoint data and the associated compliance and persistence data is shown in fig. 18. These screens may be configured to capture and aggregate medication specific information.

The medication-specific dispensing algorithm 13 then checks the prescription 4 indication and the time 464 of the last dispensing of the medication using its decision tree (see fig. 11-16) to determine if the medication can be dispensed. It then generates a screen indicating that the dose is not authorized 870 during a particular time period or whether the assigned number and the value entered by the patient 6 allow dispensing of the medication. If so, the screen displays a green dispense 868 notice and prepares the medication dispenser 16 to dispense a dose (single click medication dispense button light to green 1066). If the drug specific dispensing algorithm 13 indicates that the patient 6 should not receive opioids, even within the prescription 4 guidelines, it may generate, for example, a screen stating that the dose was not approved 870 at a particular time and providing the patient 6 with the ability to click on "dial" to call the integration support center 22, or if a problem is determined, it may display a specially designed screen or screen 874 that the integration support center 22 should be called. The type and order of screens depends on the clinical trial data capture requirements of the drug. The algorithm may contain routines that query for specific information only if certain predetermined criteria are met.

Each unproductive event of dispensing medication is tracked. At a particular point in time, the logic of the medication specific dispensing algorithm 13 will send a message to the integrated support center 22 to call the patient 6.

This embodiment allows for better prescription compliance, improved opioid safety profile, increased prescription persistence, uniform data capture, facilitates data analysis, reduces required clinical trial physician intervention, reduces trial costs, and provides real-time data capture and analysis.

Claims (29)

1. An opioid overdose screen for identifying patients with opioid overdose and/or patients who would be overdosed if taking an otherwise prescribed opioid dose, comprising: 1) iris scan pupillary measurements, and 2) one or more overdiagnostic tests for patients whose pupil diameter, when compared to the pharmacokinetic-pharmacodynamic baseline of the patient, falls: (i) a pinpoint-like pupil or mydriasis value at which the opioid dose is not dispensed/administered, and (ii) a pupil size value at which the opioid dose is safely dispensed.

2. The opioid overdose screen for identifying patients with opioid overdose of claim 1, wherein the initial opioid overdose screen comprises a standardized pupil scan that is compared to the patient's baseline pharmacokinetic-pharmacodynamic model value to determine if the opioid should be dispensed, and wherein there are questions about taking the dose and possible overdosing to the patient.

3. The opioid overdose screen for identifying patients with opioid overdose of claim 2, wherein one or a set of confirmatory tests or diagnoses (e.g., pupil responsiveness, tone or speech, cognition, SpO2, facial images, heart rate, etc.) are used to confirm: patients are at risk of overdosing if they take opioid doses, or are allowed to dispense prescribed doses.

4. An opioid-specific application (App) for controlling a drug dispenser that allows a patient/user to specify his/her language preferences, and if desired, voice prompts, commands and responses to interact with the opioid-specific App, the opioid-specific App comprising: (i) a biometric authentication module, (ii) a prescription module, (iii) a prescriber side-effect tracking preference module, (iv) a patient reminder module, (v) an interface API between the medication dispenser module and the opioid specific App on the interface device, (vi) an application program interface API between the interface device (or stand-alone medication dispenser) and the digital data capture device and/or data capture software and/or data sink device, (vii) one or more patent self-assessment screens and data sink modules, (viii) one or more patient self-test screens and data sink modules, (ix) one or more patient self-report screens and data sink modules, (x) an interface device database module, (xi) an opioid specific dispensing algorithm module, (xii) a dispensing communication and reporting module, (xiii) an interface API between the interface device and a server module of the integrated support center, (xiv) A patient reporting module, (xv) a safety controlled kit replacement module, (xvi) a GPS module, (xvii) a package insert module, (xviii) a dispenser manual module, (xix) an App manual module, (xx) a help and troubleshooting module, (xxi) a language preference module, (xxii) a voice control module, (xxiii) an App identifier module, and (xxiv) an App and dispensing unit operation training module, the opioid-specific App being patient-customized based on the requirements of the opioid-specific dispensing algorithm and the side effects and unique App serial number, if any, that the prescriber wants to track, when a drug order is electronically generated and transmitted to a data server containing a patient-specific opioid-specific App generation program, the App generator on the data server compiles (creates) a personalized opioid-specific App.

5. The opioid specific App of claim 4, wherein the patient/user may select from a list of languages to be used by the opioid specific App to interact with the patient/user.

6. The opioid-specific App of claim 4, wherein the patient/user may select voice prompts, commands and responses to interact with the opioid-specific App.

7. The opioid specific App of claim 4, wherein the App is specifically created for a patient by an opioid specific App creation program upon receipt of an electronic copy of an electronic prescription electronically submitted by a prescriber or input from a written prescription by a pharmacy or dispensing location.

8. The opioid specific App of claim 4, wherein the App replicates necessary patients, prescribers, prescriptions, pharmacies, additional information to track, side effects to track, and reminder selections, scheduling and contact information from a copy of the electronic prescription.

9. The opioid-specific App of claim 4, wherein the App information is checked and updated as needed each time a prescribed medication is dispensed with a supplement.

10. The opioid specific App of claim 4, wherein the App requires biometric authentication, e.g., iris scan, fingerprint scan, voiceprint, name and password agreement, odor or chemical footprint, specific sport, biometric card, computer generated confirmation code, or the like, or any combination thereof.

11. The opioid-specific App of claim 4, wherein the App is configured to capture certain patient self-assessments, patient self-tests, patient self-reports and/or digitally captured patient physiological, psychological, lifestyle, other medication and environmental values or information taken, and/or side-effect information that is used by the opioid-specific dispensing algorithm to generate a program-based decision tree, decide to dispense or not dispense an opioid dose, even if the prescription would authorize dispensing opioid doses.

12. The opioid specific App of claim 4, wherein the App may be configured to capture certain side effects, concurrent medication, as well as patient self-assessment, patient self-detection, patient self-reporting, and digitally captured patient information/values as directed or instructed by the prescriber for which better patient management and/or clinical trials may be needed but which the opioid specific App dispensing algorithm does not need to use to make dispensing decisions.

13. The opioid-specific App of claim 4, wherein intervals to capture certain side effects and patient self-assessment, patient self-detection, patient self-reporting and digitally captured patient values/information may be set for each tracked value/information, the time interval to capture each piece of prescribed information is determined by the opioid-specific dispensing algorithm and/or may be determined by the prescriber, e.g., every other time, once per day, every other day, every week, when a certain value is reported, as a result of another value reported within a defined range, etc., before each dispensing of a drug.

14. An opioid specific dispensing algorithm comprising a decision tree that utilizes prescription, drug dispenser, drug cassette, drug and digitally captured, patient self-assessment, patient self-testing, and/or patient self-reported physiological, psychological, lifestyle, contemporaneously taken drug and/or environmental data in a novel opioid specific diagnostic algorithm to: (i) preventing dispensing of opioids to patients who are overdosed or who may be overdosed if an opioid dose is dispensed, even if the dose is otherwise authorized by the prescription, (ii) controlling the dispensing of each opioid dose through the drug dispenser, (iii) preventing repeated administration of opioids, (iv) preventing dispensing of an expired opioid, (v) preventing dispensing of improperly stored opioid, (vi) preventing dispensing after expiration of the opioid prescription, (vii) ensuring opioid prescription compliance, (viii) preventing simultaneous dispensing of the same opioid from multiple drug dispensers, (ix) controlling dispensing to prevent early administration and to ensure maintenance of a minimum time between dispensed doses, (x) in the event that a drug dispenser senses an unauthorized attempt to open or tamper with the drug dispenser, (xi) tamper-proofing the drug dispenser by locking dispensing, and (xi) tracking early attempts to dispense the opioid as an indication of possible abuse and/or enhanced opioid tolerance.

15. The opioid specific dispensing algorithm of claim 14, wherein if a patient takes an overdose or is at risk of taking an opioid dose, the algorithm utilizes an opioid overdose diagnosis to prevent dispensing of the opioid dose even if the prescription is otherwise authorized.

16. The opioid-specific dispensing algorithm of claim 14, wherein the algorithm utilizes prescription information to determine whether the opioid in the drug dispenser is a prescribed opioid.

17. The opioid-specific dispensing algorithm of claim 14, wherein the algorithm utilizes a device tamper prompt of the drug dispenser to determine whether a drug should be dispensed or whether a drug dispenser should remain locked until an integrated support center unlocks the drug dispensing App.

18. The opioid specific dispensing algorithm of claim 14, wherein the algorithm evaluates the number of early dispense attempts to determine whether a drug should be dispensed or to lock the drug dispenser until the patient has a dialogue with the integrated support center that will make the decision to keep the drug dispenser locked or allow the patient to continue dispensing within the prescribed limits.

19. The opioid-specific dispensing algorithm of claim 14, wherein the drug dispensing algorithm checks a plurality of drug dispensers authorized to dispense the prescription opioid to ensure that the prescription dose is dispensed only once according to the prescription instructions, regardless of the number of opioid drug dispensers that the patient may own.

20. The opioid specific dispensing algorithm of claim 14, wherein the algorithm prevents repeat dosing unless authorized by a prescription or overridden by an integrated support center.

21. The opioid-specific dispensing algorithm of claim 14, wherein the algorithm utilizes prescription information to determine compliance with any particular storage requirements, such as temperature range, humidity level, etc., prior to authorizing dispensing of a dose.

22. The opioid specific dispensing algorithm of claim 14, wherein the algorithm utilizes prescription information to determine the time interval between doses.

23. The opioid-specific dispensing algorithm of claim 14, wherein the algorithm presents a specific screen on the interface device informing the patient that the opioid may be dispensed or another action (e.g., wait a specific time before authorizing the dispensing of the opioid; the medication is not approved, call the integrated support center; call the integrated support center because such medication should not be taken, etc.).

24. The opioid specific dispensing algorithm of claim 14, wherein the algorithm includes an interface in the results screen that allows the patient to click on the screen to automatically contact the integrated support center.

25. The opioid specific dispensing algorithm of claim 14, wherein the algorithm uses defined inputs and decision logic to determine: (i) whether an opioid dose should be dispensed, or (ii) not even if the prescription permits, prior to talking to the designated healthcare professional of the integrated support center, who will decide whether to keep the medication dispenser locked or allow the patient to dispense an opioid dose by unlocking the medication dispenser to obtain the permitted dose.

26. The opioid-specific dispensing algorithm of claim 14, wherein after negotiation with the patient, the integrated support center may override the algorithm lock and cause the opioid-specific dispensing algorithm to resume dispensing as prescribed.

27. An opioid specific application (App), wherein an authorization representative in the integrated support center may remotely change a prescribed dosing schedule on a patient prescription residing in an interface device or a stand-alone medication dispenser.

28. An opioid specific application (App) for compiling digitally captured and/or patient entered self-assessment, self-detection and/or self-reporting physiological, psychological, lifestyle, co-administered drugs, environmental, opioid side effects and/or PRO information/values/data not required by an opioid specific dispensing algorithm to: 1) helping prescribers and/or caregivers to better manage patients and their opioid therapy/pain management, and/or 2) to compile clinical trial information needed for regulatory submissions and/or reports, and/or for REMS and/or Prescription Drug Monitoring Plan (PDMP) reports.

29. A closed loop opioid traceability control system for controlling opioid transfer, misuse, abuse, repeat dosing, addiction, dependence, overdose, death and accidental ingestion by children, comprising: (i) a physician or prescriber, (ii) an opioid prescription, (iii) a patient, (iv) a pharmacy (pharmacist, pharmacy technician) or other medical professional and/or location authorized to dispense the prescription, (v) a data server, (vi) an opioid-specific App, (vii) an interface device (e.g., smartphone, tablet, computer, stand-alone dispensing device, etc.) on which the opioid-specific App is located, (viii) a medication dispenser, (ix) an opioid, (x) a pill box, and/or (xi) an RFID tracking device, if any, integrated in a pill, caplet, capsule or other solid oral medication form, to track the time at which the medication is ingested, and/or (xii) a self-timer procedure, it takes a picture of the patient, identifies that the opioid is being taken, and records the time at which the opioid was taken by the patient.