Flicking your wrist as your smartwatch nudges you, you find a notification alerting that it’s time to take your digital pills. You grab one from your smart medicine pack, alert your GP, and ingest it with a glass of water. Thereafter, the pill broadcasts a real-time video stream as it goes down your oesophagus and into your stomach. Your GP is simultaneously monitoring the visuals, assessing the progression of your ulcer. Afterwards, you have a video call with your GP who reassures you of the ulcer’s healing. She also notes that the digital pill contains your personalised medicine 3D-printed onto it and it will slowly get activated with your stomach’s activity. Before leaving, she reminds you to stick to the prescribed treatment plan for the best outcome. It’s a nice reminder that she’ll be monitoring your adherence via the pill’s tracking sensor. Such a treatment procedure will soon be reality. 3D-printing of multiple medicines on a single pill, known as a polypill, is already a possibility. PillCam develops ingestible capsules equipped with camera systems to visualise the digestive tract. As for a trackable digital pill, Proteus Digital Health pioneered these. While these are three separate examples, it’s not far-fetched to envision a company coming up with an amalgamation of these trio and offer a solution akin to the introductory story. With the data collected, better insights can be obtained about patients’ conditions. This will enable manufacturers and doctors to streamline treatment plans for individual patients. However, such tracking and data collection will present an additional privacy nightmare that needs to be addressed in parallel to developing the technology. You might have heard the news of Proteus, one of the leaders championing digital pill technology, filing for bankruptcy. Nevertheless, its failure does not mean the end of the depicted future or technology itself. It only signifies a steeper slope ahead of those working on bringing it to the market. Let’s see where the technology lies and what awaits it ahead. What is a digital pill? It might sound like the latest hype from Silicon Valley, especially with the “digital” prefix, but the technology behind digital pills isn’t totally new. These refer to ingestible medications with embedded electronic circuits rather than smartphone logging apps. The first instance of a swallowable medical electronic device dates back to 1957. It used radio frequency to transmit temperature and pressure readings. The next milestone in the field happened in 2017 as technological progress caught up with the invention. That year marked the FDA’s first-ever approval of a digital pill, Abilify Mycite. PillCam’s aforementioned endoscopic capsule differs in that it is destined for imaging purposes, while the Abilify Mycite is a truly digital pill for treatment and monitoring purposes. Produced by Otsuka Pharmaceutical and Proteus Digital Health, Abilify Mycite contains aripiprazole, a drug used in treating psychiatric conditions, and an ingestible sensor. The latter activates with the stomach’s acid and emits signals to a patch worn on the rib cage. The patch further communicates with an app, allowing doctors to monitor the patient’s adherence. This is a game changer for patients with severe conditions like schizophrenia and severe depression, as missing a medication can have serious consequences. Moreover, only about 25-50% of patients correctly take their medications worldwide. Poor treatment compliance leads to $100 billion to $300 billion in healthcare costs and leads to some 125,000 annual deaths in the U.S.; all of these preventable. Investors jumped at the prospect of Proteus’ technology to curb those figures. The startup thus raised over $500 million in venture capital and was valued at $1.5 billion in 2019. However, under pressure to hit milestones quickly following such investments and an abrupt termination of its partnership with Otsuka, Proteus struggled to raise more capital. Eventually, the company filed for bankruptcy in June 2020; leaving a bitter taste in investors’ mouth when it comes to digital pills; and putting a halt in realising the future treatment envisioned in the introduction. A failed company, not a failed tech “Proteus may have picked [a] therapeutic area with a degree of difficulty that’s an eight or nine out of 10, right?” said Bill Evans, managing director of digital health venture fund and research group Rock Health, when Proteus’ troubles emerged. “They may be paying the price for that tactical choice, because it’s such a challenging therapeutic modality for their particular intervention to take hold.” Indeed, Proteus’ failure reflects a failure from the part of the company and its management, not from the technology itself. In fact, studies showed that digital pills for adherence measurement indeed help in improving adherence among populations with adherence issues. An independent study put Proteus’ own technology to the test. It analysed patients with tuberculosis who use oral pills equipped with Proteus’ system. These patients showed improved adherence to their treatment, comparable to in-person medication adherence programs. The technology is still helpful for such specific patient population and that’s why interest still exists in this field. “I think someone will try to push this forward,” said Michael Greeley, co-founder of Flare Capital Partners, regarding Proteus’ fall. “They will likely face many bidders over a long bankruptcy process,” he added. Indeed, Otsuka and others are already eyeing the acquisition of Proteus’ technology. Another company, etectRx, had its digital pill that uses a removable lanyard rather than a patch approved by the FDA in late 2019. Spain-based Infármate is developing a similar solution, named SIGUEMED, to help the elderly with chronic illnesses properly take their medicine. However, the challenge that lies ahead of those companies treading the same path as Proteus did is to attract investors who will instinctively be wary of following Proteus’ ill-fated tale. But the issues around the future of digital pills lie beyond financial woes alone. Digitised but not minimised concerns Having a 24/7 sensor that tracks when and if you take a pill feels intrusive, eerily stepping into the realm of surveillance. Now consider prescribing such a treatment to schizophrenic patients who have the tendency to think that they are constantly tracked or monitored; probably not the most ideal way to get them to stick to their meds. “As a psychiatrist, I would still feel uneasy about prescribing an antipsychotic drug with that feature,” said Dr. James Levenson, a psychiatry professor for Virginia Commonwealth University School of Medicine. Moreover, Abilify MyCite is reportedly priced at $1,650 per month, or double that of the brand name drug, while the generic aripiprazole drug costs less than $20 per month. Not the best incentive for individuals or insurance companies to look into this option. More so given that a British Medical Journal paper published in 2019 concluded that there was “no evidence of better adherence with the digital version of aripiprazole compared with the non-digital version”. This is in contrast to the positive findings of the results of the later independent study mentioned before. These conflicting conclusions attest to the novelty of the digital pill solution, hence the need to further understand the best targets to benefit from it. Meanwhile, payers and providers don’t have the right justification to cover it. Of course, given the use of technology in digital pills, privacy concerns jump in the picture. The tracking nature of these pills raise further questions about who else will benefit from the data collected. What about patient autonomy in all that? Should we subjugate ourselves to a tracking device disguised in a timer? Some raised such issues as soon as the FDA gave its approval for Abilify MyCite in 2017, but authorities have not invested much into reassuring end-users regarding these issues since then. Solutions to make digital pills less hard to swallow Combined, the issues of privacy protection, affordability, management and doubt over effectiveness gave Proteus a hard pill to swallow. Nevertheless, we believe their technology holds potential. It could lead to a seamless, remote treatment experience as pictured in the introduction. However, much work remains to be done in the field. Thankfully, others are working on improving where Proteus failed. Infármate plans a cost-effective solution with SIGUEMED. Its solution comes with a trackable blister pack, alerting caregivers when patients take a pill. A companion app informs of the right time to take the pill and alerts contact persons if a mistake has been made. “Printing with electronic ink enabled us to lower the cost to that of a classic blister pack, but with a remarkable increase in added value,” said Antonio Rey, the company’s CEO. The recently FDA-approved etectRx gives patients more control over when monitoring starts. Their solution involves a removable lanyard rather than a patch, which patients can remove after taking their medicine. Such an opt-in approach could be more acceptable by patients and help build trust over time. But to further build on this trust, digital pills must comply with HIPAA or other patient privacy laws. This will help such compliance technology work for the patient rather than against the patient. Source
