BWH researchers are among the first clinicians to explore how a digital pill – in which a digital message is sent to a prescriber immediately after a medication has been ingested — could track patterns of certain drug uses, particularly in high-risk populations.

Investigations into ingestible biosensors, the technology encapsulating a drug with a tiny battery and transmitter, began about seven years ago. Now, researchers are finding that the technology offers a real-time, real-world way of monitoring patient adherence to medications, according to Edward Boyer, MD, PhD, of the division of Medical Toxicology within the BWH Department of Emergency Medicine.

Digital Delivery

“Nonadherence to medications or using medications in a manner other than prescribed poses risks, such as disease progression and addiction, to patients in some cases,” said Boyer, who recently joined BWH along with Peter Chai, MD, from UMass Medical School in Worcester where they studied ways to prevent adverse drug events, toxicity, drug interactions, poisoning and drug overdose.

“This is the technology I’ve been waiting for,” said Chai, recalling when he first learned of the digital pill concept.  As a toxicology-trained emergency physician, his first thought was to deploy the technology to look at how patients take pain medicine after an acute injury.

The digital pill technology used by Boyer and Chai includes a small gelatin capsule filled with the medication and a thin wafer (manufactured by eTectRx) embedded with a tiny battery and radio transmitter. The encapsulated pill is manufactured via a standard pill-filling machine.

Once the pill reaches the stomach where it dissolves, chloride ions activate the radio transmitter that sends a signal to a receiver where the type of medication, the number of the pill taken and time of ingestion is recorded. The information is then relayed to a cloud-based server that delivers a message to the prescriber within 5-10 minutes of ingestion.

“We can tell whether or not a patient has taken the pill, and we can get patterns of adherence and identify an overdose,” said Boyer.

The physician can contact the patient immediately if non-adherence or a worrisome pattern of use is noted.  “We are talking about the ability to do an immediate behavioral intervention for a specific medical condition and specific patient population,” he says.

From Ingestion to Intervention

The goal in using the digital pills is to detect the point at which there is a dangerous escalation in opioid use behavior. Is it related to worsening pain because of complications or something amiss after surgery? Or are they developing tolerance?  “That is the sweet spot to identify where intervention may be suitable to help potentially dangerous behavior,” said Chai.

Boyer and Chai first put the technology to use in patients with fractures seen in the BWH Emergency Department who were given oxycodone digital pill packages for pain relief.  Results from a small pilot feasibility study published in the Journal of Medical Internet Research in January 2017 showed that the technology can be successfully used through the ED with a short 10-minute learning course.

The team is currently pursuing a larger study tracking how patients take their medication, looking for signs of a developing tolerance to opioid analgesics. A key part of this investigation is that it includes patients in their normal daily environments which can include homelessness, migratory work patterns and high-risk for substance abuse. “It is fascinating to see this technology literally live and in action, especially in light of recent data from the Centers for Disease Control and Prevention about the risk of long-term opioid addiction in patients who have even short courses of oxycodone,” said Chai.

Boyer is also using digital pill technology to measure anti-retroviral medication adherence in HIV prevention. Boyer and Chai have already conducted studies showing there is no difference in the pharmacokinetics of the active medication with and without the digital pill.

The team is about to initiate another study with David Kroll in the Department of Psychiatry and the Phyllis Jen Center at BWH studying adherence to anti-depressant treatment. Since anti-depressants often require several weeks to achieve a clinical response, non-adherence early on in the course of therapy is a major course of failure.

The current average cost of $11 per pill is expected to drop, broadening the availability of the technology. For now, the team believes that the technology’s greatest applications will be in high-risk patients, such as the elderly or people with known non-compliance with high-risk medications, such as costly drugs or for high-risk conditions.