At nearly every major industry conference — from HLTH to CNS Summit, Exponential Medicine, and Rock Health Summit — speakers are talking about the benefits of decentralized clinical trials and digital endpoints. We are quite excited about the latter.
For a new drug to be approved, the manufacturer must provide the FDA with substantial evidence that it has a clinically meaningful effect on patients. It does this by providing data on endpoints, like survival or a substantial reduction in a biomarker like LDL cholesterol or hemoglobin A1c.
Digital endpoints are the newest type of endpoint. They are assessed using data captured by a sensor, typically outside of the clinic during activities of daily living. The sensor could be worn, like an accelerometer in a smartwatch used to capture motion data. It could be ingested, like a pH sensor in a digital pill used to capture acidity in the digestive tract. It could also be part of a remote sensor system, such as a microphone in a smartphone or Siri or Alexa used to assess voice.
Digital endpoints can use sensors to capture existing measures in a new way, say using a smartphone microphone to measure cough instead of relying on a patient to record episodes of coughing in a diary. Digital endpoints can also capture brand-new measurements that were not previously possible to assess. Continuous assessment of the quantity and intensity of activity, measured using a wearable sensor, can be a clinically important digital endpoint for heart failure.
The pharmaceutical industry is making real progress incorporating these new endpoints into clinical trials. It’s a welcome example of digital not being hype in health care.
To help advance this work, the nonprofit Digital Medicine Society has just released a crowdsourced library of them. It’s the first-ever crowdsourced list of pharma companies that have publicly disclosed they’ve collected digital endpoints in clinical trials.
With help from industry contributors, the library details 38 unique industry-sponsored studies that evaluated digital endpoints in new medical products or new applications of existing medical products. The digital tools used range from accelerometers to spirometers and microphones. To date, digital endpoints are being used in trials by 15 different sponsors; they include eight primary endpoints and seven Phase 3 studies.
This resource represents an encouraging trend, underscoring pharma’s commitment to realizing the promise of digital endpoints in drug development and indicating that the translation of digital measurements from pilot studies to use in drug development is already underway.
The appeal of digital endpoints
More frequent — and even continuous — objective monitoring beyond the walls of the clinic offers the possibility of more precise and accurate assessments, including identifying phenomena that have previously been impossible to measure. Arguably more important is that patients stand to benefit tremendously as the time and costs of bringing new therapies to market are reduced, the burden of trial participation on patients and caregivers drops, and our understanding of how new therapies affect activities of daily living improve.
There are other compelling reasons for pharmaceutical companies to commit resources to using digital endpoints in trials. A recent report by PWC predicts that sponsors “willing to invest in strengthening or building digital competencies may win market share, while those without sufficient investments may find themselves at a disadvantage.”
However, the time and budget required to conduct the necessary clinical trials may present too high a barrier to organizations interested in advancing digital measures for use in medical product development.
Breaking the validation barrier
To realize the full potential of digital measures in clinical research, it will be important to significantly accelerate the generation of standardized, robust evidence to support their use. Given the resources required to develop this evidence, and especially for their use in registrational trials, no single company or organization can do this alone. This is true for all biomarkers and outcome assessments, but is particularly applicable to digital measures where verification of the sensor, analytical validation of the algorithm and clinical validation of the measure itself are all necessary steps requiring different expertise.
Precompetitive collaborations offer the most obvious solution to this barrier and have been recommended as part of an optimized approach to developing digital endpoints. By sharing resources and risks, collaboratives are better placed to develop the necessary body of evidence to use digital measures to assess efficacy in registrational trials. Digital measures developed by collaboratives are also more broadly available to others for future use, including medical product developers, researchers, clinicians, and patient groups that may not have the knowledge and resources to independently develop an accepted digital measure.
Strength in numbers
Although we have yet to witness the broad adoption of collaborative approaches to the development of digital endpoints, cooperative efforts do exist. For example, C-Path’s PRO Consortium is leading an industry collaborative pursuing FDA qualification of an activity monitor-based endpoint measuring physical activity. However, valuable information, such as digital measures under development, justification for including digital measures, digital datasets accumulated during feasibility and validation studies, and lessons learned have been kept behind closed doors as medical product developers rightfully seek to safeguard their intellectual property.
Recognizing this reality, much can still be done to promote collaborative, accountable sharing in a way that continues to respect such intellectual property and competitive concerns. We could stand by waiting for increased comfort for collaborative approaches and watch the development of digital endpoints shuffle along as evidence remains siloed and industry pursues a litany of feasibility and pilot studies. Or we could recognize the current comfort level of the field and provide appropriate tools to help move it forward.
One step forward
The new digital endpoints library provides a transparent, accountable sharing of efforts from industry. Using and contributing to the library allows for others to learn what digital measures and tools are being used in industry-sponsored trials. It also shines a light on digital measures already being included in industry-sponsored trials, providing a strong signal of where digital endpoints may be most valuable in drug development and where there is already a growing body of evidence of feasibility and performance.
While the value and potential impact of the digital endpoints library is exciting, it is only a first step in supporting the continued advancement of digital measurement in drug development and beyond. The Digital Medicine Society is already pursuing ancillary projects and efforts including developing a common taxonomy and framework for the evaluation of sensors and digital measures. It also envisions supporting industry collaboratives, as the field becomes ready to engage in pre-competitive initiatives.
Our library confirms that digital endpoints are being integrated into clinical trials of new medical products. Industry has cut through the hype around digital health tools and begun using them in the development of new drugs. Now we must wait to see whether these digital endpoints fulfill their promise of more streamlined, patient-centric trials.
Jen Goldsack is the interim executive director of the Digital Medicine Society and Rachel Chasse is the society’s director of innovation. William A. Wood, M.D., is a hematologist/oncologist and an associate professor of medicine at the University of North Carolina and the UNC Lineberger Comprehensive Cancer Center.