Virtually Observed Therapy (VOT)

These are companies that are utilizing proprietary facial recognization technology to determine if a patient swallowed their medication. Similar to VOT used in certain clinical situations such as for public health projects for infectious disease (e.g., tuberculosis) or in a psychiatric unit whereby a nurse or similar health professional administers and documents that a patient took their medication, but now instead of a person actually watching, the smartphone camera serves as an intermediary. The benefits to such platforms include reduced overhead for requiring health team members watch and document, and scalability to allow VOT to occur in any setting, easing the burden of logistics for the patient and health facilities involved. Other terms adopted include Digitally Observed Therapy (DOT) and video directly observed therapy (VDOT).

AiCure

New York based Artificial Intelligence (AI) platform targeted towards capturing when a patient takes their medications focused on clinical trials and population health therapeutic areas. The platform integrates HIPAA-compliant facial recognition and medication identification to tag a patient to drug when taken. What is really interesting about the platform is that it can detect when a patient swallows the medication (such as instances where a patient may ‘park’ or ‘hide’ a drug in their mouth for later consumption or disposal during DOT), which is a really cool feature. The data is then uploaded and can be analyzed as needed, and the video of the patient taking the medication does not need an in-between step of being reviewed due to their proprietary technology. Another item to note, most of their preliminary research focused on proving their technology has included pharmakinetic studies tying together presence of drugs in the body and the tracked adherence on their platform. Most of their initial research has included ID or anticoagulation therapy at this time.

Research Data:

• Please visit their site. This company hosts a page dedicated towards their published literature.

• In-Progress based on ClinicalTrials.gov

Emocha Mobile Health

Boston based start-up with a focus on medication adherence in population health areas (e.g., ID, opioids). The system includes a HIPAA-compliant mobile app that captures video recording of a patient when they take their medication. The video subsequently needs to be reviewed to confirm that a patient took their medication. Communication is controlled through the app with nudges delivered via HIPAA secure messages alerting the patient to take their medication. Interesting feature of the app is patients can record side effects of the drug as well.

Research Data:

• No peer-reviewed literature or in-process studies found.

• Case studies listed on company website.

sureAdhere

San Diego based start up focused on tracking medication adherence for population health conditions. Noted for supporting the National Health Service (NHS) Find & Treat Tuberculosis (TB)-control program (Oct, 2017). Their platform in includes patients recording themselves taking their medication, whereupon after being uploaded to a server it is reviewed by a health care provider who then documents their compliance. The platform integrates SMS and email notifications to alert patients of missed doses, and reports can then be generated by a provider to review their adherence records. Overall, most of their research and clinical areas are focused on TB, Opioid Substitution Therapy (OST), HIV PrEP, and Hep C.

Research Data:

• Company lists a number of studies involving their platform on their website.

Bioingestible Sensors

The idea of using sensors to track adherence isn’t necessarily new, but the technology has only recently really come into its own in the past few years. It was only in 2017 that we saw the first drug with a built in sensor approved by the FDA. At this time, there are only two bioingestible sensor companies tracking medication adherence (to my knowledge at least) on the market at this time. The following profiles highlight which therapeutic areas the companies are concentrated on, and how their platforms work overall. At this time, most of these companies are using their technology for research (with capsule-enabled sensors that can contain a study drug) or trying to embed the sensor into a tablet/pill for mass consumer use. The therapeutic areas of target include specialty drugs primarily at this time - in no doubt due to likelihood of being covered by payers or other agencies.

Proteus Digital Health

Probably best known now for teaming up with Otsuka Pharmaceuticals and bringing the first sensor enabled drug to market (Abilify MYCITE).

Research Data:

• The company lists a number of studies they have published on their website.

• ClinicalTrials.gov has several studies listing what Proteus is currently investigating and JAMA has some news related to the subject as well.

EtectRx

Using their ID-Cap system to encapsulate an active drug, the cap when ingested dissolves and sends a ping to a reader that the patient wears to track their adherence. The reader is a device worn like a lanyard over the neck, and hangs over the abdomen by the patient. Overall, etectRx seems geared more towards a research niche at this time.

Research Data:

• The company does not list its studies, but Pubmed has several listed under their etectRx and those conducted by Dr. Peter Chai using the EtectRx/bio platform.

• ClinicalTrials.gov has several studies related to their ID-CAP system.

Smart Pill Bottles

The concept of having a pill bottle keep track of medication adherence isn’t anything new. You have the MEMS Cap which has been used in multiple clinical trials for over two decades at this point, which could let researchers know when the bottle was opened (and a dose was assumed taken). Funnily enough, there has been a home-brew market for a few years now with instructions for makers to create their own pill bottles which can easily be found online. However, the smart pill bottle market has steadily evolved and there are a number of new players on the field. Nonetheless, recently there has been a slew of studies lending some troubling views as to whether these systems accomplish their intended purpose of increasing medication adherence, which I have written about before. I stand by future research and designs may lead us to a better understanding in the next few years.

Note: One feature about many of these companies is that the caps they supply may not attach directly to a patients bottle depending on what pharmacy they use. Some caps are being sold for CVS/Walgreens/etc bottles or more likely they are sending their own bottle along for the patient to use instead.

AdhereTech

Perhaps one of the most well known smart pill bottle companies, AdhereTech platform focuses on a standalone cellular enabled bottle that transmit data in real-time when it is opened. This data can then be utilized by clinicians for patient management. The system also includes SMS, phone call, and live outreach to patients depending on dose history. The bottle lights up when a dose is due, and alerts patients to take their drug with chimes as well coming from the bottle. AdhereTech markets its devices as a standalone platform relying on no syncing with an app or set-up from a patient side, and lasts for 6+ months on a single charge. Now, this is not a device intended for individual consumer purchase (B2C) but for use within health systems or research purposes (B2B). One example would be the work between Avella Specialty Pharmacy and AdhereTech to monitor adherence rates in expensive medications - which honestly seems the golden area for any digital health company focused on medication adherence these days - with a focus on oncology therapy (Link to example poster research). Most of their recent clinical work has focused on the specialty market and chronic conditions including Hep C, Cystic Fibrosis, and anticoagulation therapies.

Research

• AdhereTech keeps a listing of their clinical trials on their website mixed with their press reports.

• A number of trials are also listed on ClinicalTrials.gov.

Vitality GlowCap

NantHealth has a whole line of products focused on health data integration, and includes the use of a smart pill bottle. Now, the GlowCap has an interesting history, spinning out of the MIT Media Lab by David Rose. Rose co-founded Ambient Devices, which was focused on making IOT devices, and started Vitality, which was focused on the use of an IOT smart pill bottle to track medication adherence. From there, the initial premise of B2C transitioned to B2B, and the company was subsequently sold to NantHealth. The GlowCap system works with a smart cap that attaches to a medication bottle and sends alerts to patients when to take their next dose (e.g., audible alerts and the cap lid will change colors). This data can then be shared with clinicians or other healthcare members for the patient.

Research

• There have been a number of trials published using GlowCaps, but no all inclusive list exists.

• Perhaps the best resource to see what studies have been published using GlowCaps is available on ClinicalTrials.gov

Pillsy

A rather new start-up that launched in 2017, they have created two PillsyCap products focused on medication adherence. This includes a smart pill cap for prescription drugs, and a smart pill cap/bottle for supplements (e.g., vitamins). The cap is blue-toothed enabled and syncs with a mobile app. The cap will send an audible alert when it is time to take a dose, and the app will display alerts as well for the patient to see. This data can be shared with others, such as a family member. Pillsy current market includes B2B and B2C ($39.95 on Amazon).

Research

• There have been no published clinical trials using Pillsy to date (Sept 12, 2018).

• ClinicalTrials.gov does list one study at this time using Pillsy.

Smart Pill Organizers

These companies are similar to smart pill bottles but instead of focusing on a singular medication, they organize all the patients medications on one system, and have some form of technological connection to alert and track adherence. This could include companies that have designed a smart pill box to smart automatic pill dispensers. Comparably, these devices may be more beneficial for patients with multiple medications (e.g., cost of buying multiple smart caps vs one device) or complicated medication regimens. However, many of these may require a higher cost for initial acquisition, require medications filled at a pharmacy (instead of pouring them directly into a smart pill bottle yourself), and a subscription service. Focus appears to be on B2C (Buyer to Consumer) model rather than B2B (with a focus on research) at this time by a majority of these companies. Interestingly, we are seeing a number of these companies also add the ability to incorporate drugs that are packaged into blister or strip packaging as well at this time.

TowerView Health

TowerView has an interesting system whereby a personal assistant at the company will coordinate the set-up with your providers, pharmacy, and insurance company. They will then deliver your medications in a smart pillbox. When it is time to take your dose, the pill box will chime and flash alerts, along with sending out SMS and phone reminders as needed. Patients have the option of buying the device ($399.00) or enrolling in a subscription service ($39.99/month). The difference being the subscription service also includes medication delivery and pre-sorted/packaged medications to insert into the device rather than the patient doing it themselves.

Research

• No noted publications.

• Studies are listed on ClinicalTrials.gov

MedMinder

MedMinder produces several different smart pill boxes that have different features depending on the situation. The ‘Maya’ version is unlocked, and can be accessed at any time, but the ‘Jon’ version is locked and only available for patients to open depending on the directions. Each can also be paired with medical alert features that can be worn by the patient. Both can be filled by a patient or have a pre-filled option from their own pharmacy that will package the medications in a blister pack. The devices are sold as a subscription service that charges per month to be used by a patient.

Research

• Several studies listed on ClinicalTrials.gov

• No other published literature found other than open an open paper.

Vaica

Vaica produces several different smart pill boxes and packages depending on the user. The most patient specific version is SimpleMed+ which is a weekly pill box (28 compartments at 7 days and 4 times a day dosing) that can be filled manually or have a blister pack inserted into it. The doors light up when the next dose is due and audible alerts will occur as well. All of this data is captured and then recorded via a cloud portal for clinician access and review. Patients can also sync data with the companies app, Medy. Interestingly, Vaica also manufacturers other smart medication devices focused on patient assistant tools, for clinical research, and even a smart ‘liquid medication’ tray capable of holding up to 10ml per compartment (Biodose Connect) - which I have never seen before tackled by any company.

Research

• Several trials are listed on ClinicalTrials.gov

• Vaica keeps a listing of press reports detailing some of their research, but Google Scholar also has a few publications listed.

Smart Medication Home Assistant

Take your home voice assistant (e.g., Google Home, Amazon Alexa) and imagine it had a baby with a smart pill organizer, and then you have these new devices that are entering the market. It probably comes as no surprise that entrepreneurs have explored how to integrate home voice assistant programs or similar virtual technology into a medication adherence platform, as there have already been discussions about Amazon Alexa serving as a tool to remind patients to take their medication at home. The benefits to these platforms is that it could expand patient care beyond just dispensing and tracking adherence, but also as another level of patient engagement, capable of answering questions or serving as a hub for patient support. Most of these platforms also work by using compliance packaging solutions (e.g., strip or blister packaging) or having the patient fill them manually. So that being the case, the following are devices that are both a medication dispenser and have some virtual integration with a teleservice, AI, or voice assistant. Overall, we can regard these new devices as a sort of digital wellness coaches in the home.

Pillo

Getting alot of of press for raising over $100K on Indiegogo, Pillo is perhaps one of the best known robotic home medication platforms coming to the market at this time (perhaps in no small part due to its googly eyes). Based in Boston, MA, this companies home medication assistant robot is built with a medication dispenser (pre-loaded by the patient), a camera and video interface, and voice assistant. Not only can it remind and dispense medications to patients, but also answer questions and play music. Currently it is expanding its services so it is unknown what therapeutic areas they are targeting, but based on their website they are looking for partners ranging from PBM, pharma, and others. Lastly, Pillo allows integration of other health information collected from mobile apps and wearables to monitor health endpoints (e.g., calories, dietary intake).

Research:

• There is no current publications or studies related to the Pillo system.

Catalia Health

Seeking to enhance patient engagement surrounding medication adherence, Catalia Health created Mabu, a home robot that can interact with patients throughout the day. The platform seeks to understand patient behaviours and personality in order to better fit their needs and create helpful nudges for health purposes. Mabu can be used to tackle diseases and specific needs of a patient based on their medical history, and communicate with their health team. Now Mabu doesn’t sort or dispense pills to patients, but managing adherence seems to be one of its main purposes so I have it on this list.

Research:

• There is no current publications or studies related to the Catalia system.

Spencer Health Solutions

Spencer is a robot smart pill dispenser that uses pre-filled strip packaged drugs to alert and give patients their medications in the home setting. Focused on their ‘Circle of Care’ with the pharmacist playing a large role in preparing and coordinating medications for the patient using Spencer as a hub in the patient home for medication management. While Spencer doesn’t have an AI or similar built in, it does incorporate communication with a pharmacist through the system, and allows outside data to be collected and uploaded (e.g. blood pressure, SMBG data). Spencer has also recently partnered with Phillips as well, which seems to go along with Phillips earlier Medido design.

Research:

• There is no current publications or studies related to the Spencer system.

Patient Reward Platforms

Behavioral economics is an interesting thing, with multiple studies suggesting that rewarding patients financially could help lead to healthy behaviors (e.g., smoking cessation). Taking that into consideration, paying patients to take their medication seems a no brainer. Currently, many of these companies are testing their platforms within health institutions so it has yet to be determine which platform is yielding the ‘best’ result in improving adherence. Most of these companies are based around a mobile app at this time, and despite not being hardware focused, due to the type of intervention I am placing them here (as I have no intention in creating a list of medication adherence apps at any time - there are just to many).

Wellth

A new company based in NYC that pays patients to take their drugs (kindof). In essence, the platform works whereby a patient enrolls into the Wellth system, and everytime they are to take a dose of their medication, they use the Wellth app to verify they took the drug (by scanning it). The mechanic is that the patient will be given a set amount of money to be adherent for a set time, and failure will lead to lost money (essentially loss incentives). Currently the company is focused on chronic disease management and post-discharge care.

Research:

• ClinicalTrials.gov lists several studies using Wellth

Sempre Health

Sempre takes a different tactic to encouraging patients to be adherent. Patients are enrolled and receives a discount code that will lower the copayment of their drug at the pharmacy - as long as she fills on time. The patient will not be penalized if they refill late (in other words the copayment will not be higher than covered), but the benefit is that on-time refills will be rewarded, with he assumption that a patient that picks up their drug may be more adherent.

Research:

• Sempre states they have internal data showing the value of their program but no published literature.

HealthPrize

Perhaps the oldest and most well known company in this category, HealthPrize has been around since 2009 and has raised over $13M for its platform to get patients adherent and informed. You see, their platform works on a gamification scheme where patients are to aim for streaks of habits (e.g., taking their medication) and will receive an award. Additionally, patients can also engage in medical learning to increase their health literacy, making this platform a bit more holistic.

Research:

• The company lists a page dedicated towards their research as white papers.

Smart Injectable Devices

While most of the earlier platforms discussed have focused on oral medication therapies, there is ample room to use sensors and other digital technologies to assess adherence in different drug delivery devices. Injectables make up a large part of special medications amongst patients, especially those patients that use insulin or biologic therapies. With that in mind, the following companies have created smart injectable devices that are standalone or attach directly to an injected drug product to track adherence. I am not including timers or low tech solutions at this time and only those that integrate the data widely and can be accessed and shared with clinicians for medication management.

Note: One company worth mentioning that kinda fits here is HealthBeacon, a Dublin based start-up that has a Smart Bin that can track adherence with injectables when the needle/syringe is disposed. Lastly, I have not included smart pens from pharmaceutical companies at this time (Such as what Eli Lilly is currently doing), I may come back and update this after those products get further along and enter B2B or B2C markets.

Insulog

The Insulog was launched on crowdfunding site IndieGoGo, raising more than $45,000. The snap-on device, which costs $199.99, goes on the end of the insulin pen and keeps track of how much insulin is injected. This information is paired with a mobile app and then serves as an electronic diary. The app can also incorporate data from other devices and data such as blood glucose levels collected from another platform.

Research

• No identified research or publications.

Companion Medical

San Diego-California-based Companion Medical's sleek InPen uses insulin cartridges. The InPen, which costs $665, offers data reporting, a built-in temperature sensor, a dose calculator, and a dose reminder. All this is paired with an app for the patient to access. The InPen has received FDA approval and is only available in the United States. Patients need a prescription for the InPen to get it via mail, though some insurance plans may cover it.

Research

• No identified research or publications.

Gocap

Common Sensing of Cambridge, Massachusetts, is focused on creating smart devices, and the GoCap is its first product. The smart cap goes on the insulin pen, replacing the existing cap, like the InPen. The GoCap also tracks insulin dose and temperature, provides reminders and reports, and has an app to keep track of everything. The GoCap also keeps track of the amount of insulin in a pen. In addition, it has a sensor that monitors how much insulin is depleted out of the clear side of the pen that it covers. The GoCap is in Beta testing.

Research

• A study was listed on ClinicalTrials.gov

Smart Inhalers

Not to be outdone on just smart devices for injectables, there are also companies looking to track adherence with inhalers on the market. This sector is rather interesting as it has slowly matured in the past five years and now we see a few companies that have now carved out this market niche for themselves. The most obvious use of these products has been disease management for Asthma and COPD (e.g., a patient starting to overuse their SABA may be worth investigating). Now, some of these companies could just as well be classified as DTx (due to the disease management side), but since they deal with medications they are on this list.

Note: Several companies such as 3M, Amiko (though this one has some interesting press and partners with Teva I may end up changing my mind), and Hewlett Packard Labs have created/designed smart inhalers but due to no current B2B or B2C model are not included in this list.

Adherium

Originally called SmartInhaler, but changed their name, this New Zealand company has been in the smart inhaler market for over a decade. Their market is B2B focused on clinical trials, but lately has moved into the B2C market with their new product line called Hailie. They produce sensors that inhalers are inserted into for almost every inhaler on the market at this time. Users activate the sensor when taking their medication and data is captured and uploaded for clinical review depending on the setting (e.g., research, public health, medication management).

Research

• Clinical studies noted on ClinicalTrials.gov under Adherium and SmartInhaler

• Again, publications noted under Adherium and Smartinhaler name.

Propeller Health

Getting alot of recent press related to their use in clinical settings, Propeller Health manufacturers a number of sensors (think of them as buttons) that can attach to multiple inhaler types (e.g., Diskus, MDI, Respimat) and when pressed will send a record to a mobile app on the user smartphone to track adherence. The app also keeps a daily forecast to alert patients to when they may need their inhaler. Data is uploaded in realtime for review by relevant parties for clinical management or oversight.

Research

• A number of studies listed on ClinicalTrials.gov

• Publications listed on PubMed.

• See their webpage on selected research.

Cohero Health

Cohero produces a line of sensors, the HeroTracker, that attack to MDI and Diskus inhalers to track medication adherence. The data is collected and then uploaded to an online database for access by clinicians, researchers, or insurance companies - while patients can review their data on a mobile app. They also produce a smart spirometer as well.

Research

• Study listed on ClinicalTrials.gov

Blister Pack Adherence

I was a bit flummoxed when starting to make this section. You see, theres a number of companies creating devices that can track removal of medications from a blister pack that drugs are sometimes dispensed in. The thing is, in the US, most drugs come in an amber vial, but overseas many drugs come in blister packaging for unit-dosing. But, there are a few exceptions exist in the US, and the biggest one is oral birth control (which was argued to help increase adherence and other therapeutic reasons). So, while many of these devices could theoretically be attached to any blister pack (e.g., ibuprofen, PPI, vitamins), they are currently being marketed towards the oral birth control market. So, with that being the case, this list includes any such sensor to attach to blister packs to track birth control medications as a main purpose by said companies.

Popit

A rather unique device, called the Popit Sense, that clips directly onto the blister pack. The device syncs with an app that alerts you to take your medication. The device (using proprietary technology [movement, touch, sound]) can then detect when a tablet was removed from the blister pack.

Research:

• Popit has completed some clinical research using their product.

Aavia

A smart blister pack container in which a patient would insert their birth control blister pack to track adherence. The device will sync with and app that will let the patient know when to take their dose and keep track of adherence. The device can then detect if a medication has been removed from the blister pack.

Research:

• No research or publications were found related to the Aavia system.