By Deborah Borfitz

October 14, 2020 | Broader adoption of digital biomarkers in clinical trials is dependent on their regulatory approval, and data quality remains the big hurdle, according to Ariel Dowling, director of digital strategy at Takeda Pharmaceuticals, who led a workshop on wearables at the recent Bio-IT World Conference & Expo Virtual. She presented two specific use cases of digital biomarkers for clinical validation and as a primary endpoint for internal decision-making.

The benefits of using wearables in trials is that they provide objective measurements of compliance and daily activity, can help identify the right participants (based on inclusion/exclusion criteria, their compliance, or changes over the course of a study), and generate needed data from continuous monitoring in remote environments to “fill gaps in current knowledge,” Dowling says. Challenges include operational complexity, privacy and security issues with “BYOD” (bring your own device) studies, and the risk of alarm/alert notification fatigue among study subjects.

In the first case study, Dowling discussed creation of a new digital biomarker used in a narcolepsy trial to measure night-to-night variability in sleep patterns as collected by a fit-for-purpose portable EEG device. The study enrolled 16 patients with the sleep disorder and another 16 healthy age- and gender-matched controls.

During the two-night inpatient segment of the study, participants were put on both nocturnal polysomnogram—the gold standard overnight diagnostic sleep study—and the portable EEG. A maintenance of wakefulness test (used to assess the efficacy of a sleep disorder treatment) was then done while they wore both devices, she says. Enrollees then wore the portable EEG device at home for five nights.

An ECG chest patch measuring heart rate and a wrist-worn accelerometer tracking movement, sleep, activity level, and intensity were also used in the study, Dowling adds. Additionally, patients completed an electronic patient-reported outcomes questionnaire assessing sleep quality and narcolepsy symptoms.

In the second case study, a digital biomarker was used in an early-stage clinical trial to quantify the effectiveness of a drug on reducing falls in Parkinson’s disease patients. The goal of the study was to guide internal decision-making about whether to move a drug candidate into a phase 3 pivotal trial and did not require approval by the Food and Drug Administration, she notes.

The study involved a two-minute dual-task walking test (simultaneously walking and trying to do subtraction) after participants had been on the drug, or a placebo, for six weeks. Falls are a rare event, making them hard to assess via an early-phase study, so gate variability as measured by a digital wearable sensor was used as a surrogate, Dowling explains.

At Takeda, Dowling advises clinical teams on the selection of digital devices, conducts due diligence on vendors, develops digital sensor implementation protocols and risk mitigation strategies, and assists with data analysis plans for device data. She was previously a senior clinical data scientist at Biogen, where she oversaw the analysis of data from wearable sensors deployed in clinical trials for Parkinson’s disease.

Editor’s Note: Even if you missed the start of the event, Bio-IT World Conference & Expo virtual is still live. Register now for on-demand presentations.