Need to Know:
- Wearables can be a value-added aspect to data collection in clinical trials, to complement electronic Patient Reported Outcomes and electronic Clinical Outcome Assessments.
- Central nervous system and cardiovascular spaces continue to be on top in integrating wearable or sensor devices in clinical trials, but rare diseases and oncology are not far behind.
- FDA guidance on validation for wearables exists but the onus is on makers and sponsors to seek additional regulatory guidance.
The boon of remote monitoring such as sensors and trackers in decentralised clinical trials (DCTs) shows no sign of slow down, but the onus is on wearable makers as well as study sponsors to ensure there is proper device validation.
As reported in an exclusive analysis by Clinical Trials Arena, wearable sensors and tracking devices in DCTs averaged at 42 clinical trials per year between 2010 and 2014. But this has consistently increased starting in 2015, breaking the 200-study mark last year. The biggest jump was seen between 2020 and 2021, rising by 44 trials from the previous year. Remote monitoring that involves wearables are designed to track trial participant outcomes between regular onsite visits, while also reducing overall visit numbers.
In an advance in the DCT landscape, long-established assessment tools such as electronic Clinical Outcome Assessment (eCOAs) are now supported by wearable sensors and tracking devices. Wearables enable a broader view of the patient journey as it complements and enhances electronic Patient Reported Outcome (ePRO) collections, adds Nico O'Kuinghttons, vice president of commercial, DCTs at Huma.
The different digital solutions can allow for broader and better data collection, O'Kuinghttons says. Algorithms allow for information collection that can complement and allow a fuller assessment of surrogate endpoints.
Diseases with most clinical trial remote monitoring
In terms of the respective therapeutic spaces employing wearable sensors and tracking devices, Clinical Trials Arena reported they are most used in central nervous system (CNS), metabolic space, and respiratory disorder trials. CNS has always been a frontrunner and innovator with sensors because many trial endpoints have been activity-based which sensors capture well, says John Reites, CEO at THREAD, a DCT service provider. According to GlobalData Clinical Trials database, there are 56 ongoing clinical trials employing sensors in the CNS space.
There is also heightened interest in rare diseases such as muscular degenerative diseases where walking, eating, and movement matters, as well as dermatology where sleep and scratching patterns can be detected by sensors, Reites notes. Oncology is also a space with a growing interest in sensors to capture movement between visits, to indicate a treatment allows a person to become less sedentary.
The future of sensors includes new forms of clinical trial endpoints such as electronic Device Reported Outcomes (eDROs), Reites says. The next five years will see many more options in terms of how these wearables can generate quality data in a clinical study, providing comfort to physicians, patients, and regulators, he adds. Some examples of the next-generation sensor endpoints include voice data capture for voice and tonality, aspects that cannot be captured in a traditional eCOA, he notes.
Wearable, sensor data validation necessary
O'Kuinghttons says, considering the wearable and sensor explosion, key questions tech maker needs to consider include: What is the validation process of data generated? What’s the validation threshold that the study could recognise? What data is as good as going into a doctor’s office?
A wearable for a study must be able to demonstrate to the regulatory entities that the data will be reliable to validate endpoints. There is regulatory guidance, particularly from the FDA, on validation for wearables and sensors but it is broad, O'Kuinghttons says. Rather, wearable makers and sponsors are encouraged to come to the agency for further guidance.
The onus is on both the wearable maker as well as the trial sponsor to invest in research demonstrating validation, O'Kuinghttons adds. In terms of the evidence threshold for high-quality data, a recent article posited that digital therapeutics should have at least one published, randomized controlled trial (RCT) for efficacy validation. Digital therapeutics are defined by the FDA as “software intended to be used for one or more medical purposes... without being part of a hardware medical device,” and where the purpose is “treatment or alleviation of disease”.
“There are evidence standards for sensors (medical devices and consumer wearables) as some of the endpoints derived from these devices are approved as protocol endpoints,” Reites says. There is also a volume of publications available supporting the validated use of sensors, he adds.
Standardisation among wearables ideal
While sensors and tracking devices will eventually go through standardisation, in the meantime the market will be challenged with developing standardised means to the technology’s use and application, O'Kuinghttons notes. However, he adds: “I don’t think it’s naïve to say in five years we will begin to see signs of validation standardisation across certain therapeutic areas.”
An example on standardisation could be made in the cardiovascular space with electrocardiograms, O'Kuinghttons says. But there are also disease spaces like the CNS space where standardisation may take longer with numerous digital endpoints presently in the exploration phase, he added. “It will eventually depend on the amount of use cases seen.”
Although InfoBionic’s remote cardiac monitor MoMe Kardia is used primarily for the diagnostic market and a lesser extent in clinical trials, high fidelity remote monitoring is still essential in both settings, says company CEO Stuart Long. Remote monitoring in pharma is gaining momentum but this has always been the case in the cardiology space since the 1960s. As patients continue to be treated in a virtual setting – either in hospital step-down units, clinical trial sites, or at home – the heightened need for data acuity remains paramount, he adds.
As for other hurdles, a key question for wearable designers is whether the device is the right fit for a specific trial endpoint, especially when an average study can recruit in more than 20 countries and the devices are not cleared in every country today, Reites says.
On Clinical Trials Arena, we’ve been obsessed with DCTs that we’ve built our own tracker. The tracker analyses 12 years of data on DCTs worldwide, based on clinical registry protocols, research papers, and press releases, as curated by GlobalData, the parent company of Clinical Trials Arena. You can find the complete analysis here, and a specific investigation on direct-to-patient remote drug delivery in clinical trials here.