Digital Medicines: A Solution to Medication Nonadherence?

Spending in health care continues to climb: a recent report by the American Medical Association estimated health spending in the United States increased by $3.5 trillion in 2017. 

In conversations about avoidable health care spending, discussions inevitably turn to the topic of medication nonadherence, which is an area of medicine that has long needed improvement. In March, OptimizeRx released the results of a survey that found medication nonadherence could be responsible for up to $528 billion in costs as a result of health consequences, illnesses, and deaths from nonoptimized medication regimens.

However, the reasons for medication nonadherence are complicated. In the OptimizeRx survey, 34% of physicians said a patient’s desire to not take pills led to unfulfilled prescriptions, while 31% said patients already taking too many pills were a factor in prescriptions not being filled. 

In addition, OptimizeRx found approximately three-quarters of doctors are not tracking their patients’ prescriptions. This can affect how medicines are working in the real world, R. Scooter Plowman, MD, MBA, MHSA, MSc, medical director at Proteus Digital Health, said in an interview. 

“One of the great challenges facing physicians and other providers at the point of care is distinguishing challenges of effectiveness from challenges of adherence,” Dr Plowman said. “When prescriptions are not working, not taken, or taken incorrectly, this results in delayed diagnoses, delayed effectiveness, unnecessary adverse effects, overdosing, [and] underdosing,” which can result in significant medication wastage.

Directly observed therapy

A patient may not even intentionally miss a prescription, and can miss a dose due to a cognitive defect associated with a mood disorder or mental disorder such as depression, bipolar disorder, or schizophrenia, said Timothy Peters-Strickland, MD, vice president of Global Clinical Development at Otsuka Pharmaceutical Co, Ltd. A study recently published in the Journal of Psychosomatic Research found patients with depression were twice as likely to be nonadherent than patients who were not depressed.

Traditionally, the only way for a physician to know for sure whether a patient has taken a medication is to watch them ingest it on-site in a health care setting. But this solution has its own set of issues with regard to creating an undue burden for patients, said Mitchell DeKoven, MHSA, senior principal of Health Economics and Outcomes Research at IQVIA.

“The idea of directly observed therapy used to make sense, but recent research has shown that [directly observed therapy] DOT may have minimal effectiveness for improving treatment outcomes, as well as encroaching on patient autonomy, exerting an additional patient burden and challenging the long-term feasibility from a health system/provider perspective,” Mr DeKoven said.

“Totally contrary to the patient centricity that we strive for in health care, DOT requires patients to rearrange their lives, jobs, transportation, etc., to meet the schedules and convenience of health care workers,” Dr Plowman said.

Wirelessly Observed Therapy

A new method to track medication adherence has emerged in recent years with the advent of digital medicine, which combines traditional oral medication with a digital sensor that tracks when a pill has been ingested by a patient. The pill sensor communicates with a patch on the patient’s body, which then gives a timestamp of when the medication was taken and is tracked in an app, Dr Peters-Strickland said.

In 2012, the US Food and Drug Administration approved the ingestible sensor used in digital medicines through its automatic class III designation (de novo) pathway. The manufacturer, Proteus Digital Health, then began developing and studying the effect of digital medicines for medication adherence in patients, eventually publishing studies on adherence with treatments for tuberculosis, hypertension, diabetes, and hepatitis C. Digital aripiprazole was approved by FDA in November of 2017 as the first medication with a digital tracking system, and in January 2019, Proteus announced patients were using digital medicines to improve adherence for oral chemotherapy cycles. 

“Digital medicines could certainly make an impact from an adherence perspective,” Mr DeKoven said. “Smartphone-based technologies, digital pillboxes, and ingestible sensors (eg, medication reminders, digital observation of pill-taking) can all play a role in monitoring adherence, in a patient-centric approach.”

A Conversation Starter

Dr Peters-Strickland, who is also a psychiatrist in Norristown, PA, said that anecdotally, his patients taking digital medicine regimens have seemed to tolerate the transition well. However, more importantly, the data provided by digital medicines, like digital aripiprazole, give him a way to broach conversations with patients about their medication-taking patterns. 

If a patient is not taking a medication due to an adverse event, a provider may not traditionally know until the next scheduled appointment. But through a digital medicine regimen, the physician has that data in real time, Dr Peters-Strickland said. 

“When you put all those things together, that is a lot of information that we’ve never had before,” he said. The physician has greater insight into what is going on. “[If] something happened, there was a change from the pattern, you can clearly see it when you put all of this data together. To me, it’s an opening to start that conversation.”

Digital medicines can also spur conversations about cost, Dr Plowman added. As patients are taking more medication and the cost of prescription medications rise, many patients are bringing up prescription costs with their physicians. OptimizeRx found in their survey that 90% of physicians feel it is their role to discuss health care costs with patients, and 73% said a patient’s responsibility for cost is an important consideration when prescribing.

“Costs and financial wellness are often uncomfortable conversations and rarely discussed between patients and providers, and digital medicines are one tool to increase transparency and facilitate challenging conversations,” Dr Plowman said.

Digital medicine could also be a tool in remote areas, helping providers to determine which patients need in-person follow-up based on medication adherence, experts said.

“Similar to telemedicine, digital therapies could play a significant role for patients in remote/rural locations, minimizing their travel time to providers ([an] indirect cost burden to health care) thereby increasing their productivity,” Mr DeKoven said.

Privacy concerns

Dr Plowman said Proteus receives a lot of inquiries about privacy and security concerns surrounding digital medicines and noted that the data is always controlled by patients, who decide with whom they share. “They can choose to share the data with their family, for example, or with their health care team,” Dr Plowman said, who noted that users have not generally expressed privacy concerns about digital medicine to him.

One of Dr Peters-Strickland’s initial objections to the program was that the technology collected unprecedented data on patients. “You can’t look at it that way,” he said, noting he changed his perspective when he realized how the data could help his patients and aid him in making more objective decisions.

In the case of digital aripiprazole, patients can opt into data that will tell a provider when they are at rest and can provide information in the app about their mood on a given day, which are all conversation pieces that can help develop a relationship with a patient and engage in shared decision-making, explained Dr Peters-Strickland. 

“Once you can develop that kind of relationship with your patient, then you can kind of figure out anything,” he said.

ADOPTION Challenges for Digital Medicine

Digital medicine is by no means widespread as of yet, and the current data is collected by the manufacturers of the medication. In addition, digital medicine is expensive compared with generic versions of the drug: digital aripiprazole costs $1650 per month for treatment compared with $30 to $40 per month for a generic.

“The reduction of cost-offsets in the health care system, as well as improved adherence, which research has repeatedly shown leads to improved outcomes, will certainly be a significant part of the value proposition for digital medicines,” Mr Dekoven said.

The idea has also yet to be adopted by third-party payers, who Dr Plowman said “are both intrigued and enthused” by the data. He said the next goal is to demonstrate value-added benefit to patients, physicians, and the health care system. “Many physicians have not historically considered medication adherence a part of their responsibility, in large part because they didn’t have access to such data. Likewise, with new data comes new responsibility both for the patient and the provider, and this requires new processes,” said Dr Plowman.

Future of digital medicines

In the meantime, Proteus is beginning to create value-based contracts with certain providers, even fronting the cost of the digital medicines for at least one health care system, Dr Plowman said. They have partnered with Desert Oasis Healthcare in Palm Springs, CA, which cares for over 70,000 mostly Medicare patients, and the provider is only paying for the medications after greater than 80% adherence and clinical effectiveness.

Ultimately, digital medicine will need time to be accepted and adopted, and is also not intended for every patient or therapeutic area, Dr Peters-Strickland said. “With any paradigm change in medicine broadly and in mental health specifically, I think it just takes time,” he said. “Doctors aren’t used to it. Patients aren’t used to it. I think the key to me is what’s going to add value for the patient. That’s first, and then obviously for the physician and the health care system.”

Dr Plowman said he believes the future of digital medicines is bright. “I cannot imagine a world in twenty years when our medicines are not all digital objects, measuring themselves, auto-assessing effectiveness, maybe even self-dosing in accordance with tightly controlled physician-directed protocols.”