The term “digital endpoint” is often used to describe clinical trial endpoints that use sensors such as smartphone microphones, wearables and digital pills to allow for more frequent and objective remote monitoring of patients during clinical trials. Given the recent increase in interest in these novel endpoints, regulators, innovators and investors should be aware of key global trends related to the development and use of such endpoints, as well as the associated clinical, privacy, cybersecurity and other legal risks.
What is a digital endpoint?
For a new drug to be approved in the United States, the manufacturer must provide the Food and Drug Administration (FDA) with substantial evidence that the drug is clinically meaningful. The National Medical Products Administration (NMPA) in China, the Medicines and Medical Devices Agency (PMDA) in Japan, the Medicines and Healthcare Products Regulatory Agency (MHRA) in the United Kingdom, and the European Medicines Agency (EMA) in the . To provide evidence of a drug’s efficacy, manufacturers provide endpoint data, which are measurable outcomes used to address the objectives of a clinical trial.
Digital endpoints are a new type of endpoint. These endpoints are assessed using sensor-generated data that is often collected outside the clinical setting, such as during a patient’s daily activities. Digital endpoints can capture participant pools and real-world experiences. As noted in recent FDA guidance, although racial and ethnic minority groups are disproportionately affected by certain diseases, they often take existing measurements in new ways, while also being able to record new measurements that were previously inaccessible. Rather than relying on subjective assessments of participants’ progress on intermittent dating, researchers could record objective data on participants’ daily lives. In addition to providing more precise and accurate assessments, digital endpoints also significantly reduce the time and costs associated with participating in trials, especially for those with physical or cognitive limitations or time constraints. This, in turn, enables manufacturers to open up clinical trials to a more diverse and representative population that has hitherto been underrepresented in clinical research. This is due in part to the frequency of study visits required and other resource constraints. Using digital endpoints in clinical trials can alleviate some of these burdens.
The current regulatory environment affecting digital endpoints
The US has not yet embraced digital endpoints to support the approval of new drugs. However, in December 2021, the FDA released a draft guidance providing advice on the use of digital health data capture in clinical research, suggesting regulators accept that digital endpoints may arise in the short-term to support drug approval.
Outside the U.S., there appears to be a consensus among global regulators on the use of digital endpoints or — at least digital tools — in clinical trials:
- China’s State Food and Drug Administration has issued clinical trial management guidelines stating that sponsors can use digital technologies to remotely manage clinical trials.
- Japan’s PMDA similarly recommended that sponsors look for alternative ways to maintain trial participation during the Covid-19 pandemic, such as remote monitoring.
- The UK clinical trial landscape is currently in a state of change post-Brexit and new rules are expected soon. However, the MHRA has recently recognized that real-world data collected through technology can have a role in clinical research and randomized controlled trials, including regulatory decisions related to clinical trial design.
- The EU EMA has published guidance on the qualification of digital technology-based approaches to support drug approvals, and a draft guidance on electronic systems and electronic data in clinical trials is being developed by the Good Clinical Practice Inspector Working Group.
Regulators have also been working with industry to help advance the acceptance of digital endpoints.This Society for Digital Medicine and its partners from Anthem, Biogen, Eli Lilly, Evidation, Janssen, Merck, Pfizer and Savvy Co-op recently launched a toolkit to facilitate the use of digital endpoints as payer evidence in reimbursement decisions for new drugs. The 3Ps of the Digital Endpoint Value Toolkit were developed following a series of workshops that brought together regulators, health technology assessors, public and private payers, industry sponsors, health economists, and clinical and patient experts .
Legal challenges of developing and using digital endpoints
In developing digital endpoints, innovators are considering the associated risks to trial participants, including clinical, privacy, and security risks:
- A key clinical risk is that participants may be exposed to digital health technology (DHT) properties used to measure digital endpoints, such as skin-contact components. Another clinical risk may arise from DHT collecting erroneous or incomplete data due to lack of participant compliance or technology-related issues. For example, the MHRA emphasizes the importance of reliable data, regardless of source, and that any tools used in experimental settings, including DHT, must be properly validated.
- Privacy and security related risks include the potential disclosure of personally identifiable information through DHT and End User License Agreement violations or attacks by bad actors. For example, EMA emphasizes compliance with applicable EU data protection requirements, as sensitive health data processed is critical. Innovators must also consider consumer protection-related issues related to terms of service that allow data sharing with DHT manufacturers or other third parties.
- While digital endpoints can help increase the diversity of clinical trials, innovators must address the risks of bias inherent in the data, as well as the potential risks of unfair use and deployment of DHT itself.
Innovators, whether creating or investing in DHT, or considering deploying DHT in their clinical trials, should continue to evaluate and optimize their use of digital endpoints to minimize these risks, including security testing and implementation of DHT Security measures designed to protect data are collected and transmitted by DHT.
in conclusion
As digital endpoints continue to be evaluated, innovators are working toward a future where these results can replace traditional clinical endpoints in regulatory approval and approval submissions and regulation.
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