The term “digital endpoints” is often used to describe clinical trial endpoints that use sensors like smartphone microphones, wearables, and digital pills to allow more frequent, objective remote monitoring of patients during clinical trials. In light of the recent increased interest in these novel endpoints, regulators, innovators, and investors should be aware of the key global trends with respect to the development and use of such endpoints, as well as the associated clinical, privacy, cybersecurity and other legal risks.
What are digital endpoints?
For a new drug to be approved in the U.S., the manufacturer must provide the Food and Drug Administration (FDA) with substantial evidence that the drug has a clinically meaningful effect. The National Medical Products Administration (NMPA) in China, the Pharmaceuticals and Medical Devices Agency (PMDA) in Japan, the Medicines and Healthcare Products Regulatory Agency (MHRA) in the UK, and the European Medicines Agency (EMA) in the EU similarly evaluate the efficacy of a drug for its approval. In order to present evidence of a drug’s efficacy, the manufacturer provides data on endpoints, which are measurable outcomes used to address the objectives of a clinical trial.
Digital endpoints are a novel type of endpoint. Such endpoints are assessed using sensor-generated data that is often collected outside of a clinical setting, such as in a patient’s daily activities. Digital endpoints can capture pool of participants and real-world experiences. As noted in a recent FDA guidance, despite being disproportionately affected by certain diseases, racial and ethnic minority groups are frequently existing measurements in new ways, while also enabling the recording of new measurements that were not previously possible to access. Rather than relying on subjective assessments of the participant’s progress at intermittent appointments, researchers can record objective data throughout a participant’s daily life. In addition to providing more precise and accurate assessments, digital endpoints significantly reduce the time and costs associated with trial participation, particularly for those with physical or cognitive limitations or time constraints. This, in turn, allows manufacturers to open clinical trials to a more diverse and representative population hitherto underrepresented in clinical research. This has been true in part to the frequency of required study visits and other resource constraints. Using digital endpoints in clinical trials can relieve some of these burdens.
Current regulatory landscape affecting digital endpoints
Digital endpoints have not yet been accepted in support of new drug approvals in the U.S. However, in December 2021, the FDA published a draft guidance providing its recommendations on the use of digital health data acquisition in clinical investigations, signaling that regulatory acceptance of digital endpoints in support of drug approval may occur in the short-term.
Outside of the U.S., there appears to be a global regulatory consensus on the use of digital endpoints or—at least, digital tools—in clinical trials:
- China’s NMPA has issued guidance on the management of clinical trials, explaining that sponsors may use digital technology to remotely manage clinical trials.
- Japan’s PMDA has similarly recommended that sponsors find alternative approaches to maintain trial participation during the Covid-19 pandemic, such as remote monitoring.
- The UK’s clinical trial landscape is currently in a state of flux post-Brexit, with new rules anticipated soon. However, the MHRA has recently recognized that real world data collected by technology can play a role in clinical studies and randomized controlled trials, including in respect of regulatory decisions relating to clinical trial design.
- The EU’s EMA has issued guidance on the qualification of digital technology-based methodologies to support approval of medicinal products, and a draft guideline on electronic systems and electronic data in clinical trials is under development by the Good Clinical Practices Inspectors Working Group.
Regulators have also been collaborating with industry to help advance the acceptance of digital endpoints. The Digital Medicine Society and its partners from Anthem, Biogen, Eli Lilly, Evidation, Janssen, Merck, Pfizer, and Savvy Co-op recently launched a toolkit to facilitate the inclusion of digital endpoints as evidence for payers in reimbursement decisions for new drugs. The 3Ps of Digital Endpoint Value toolkit was developed following a series of workshops bringing together regulators, health technology assessment bodies, public and private payers, industry sponsors, health economists, and clinical and patient experts.
Legal challenges in the development and use of digital endpoints
As they develop digital endpoints, innovators are considering the associated risks to trial participants, including clinical, privacy, and safety risks:
- A key clinical risk is that participants could be physically affected by features of the digital health technology (DHT) used to measure the digital endpoints, e.g., skin contacting components. Another clinical risk could be presented by the collection of erroneous or incomplete data by the DHT, either due to lack of participant compliance or technology-related issues. The MHRA, for example, has emphasized the importance of robust data regardless of source, and that any tool, including DHT, used in a trial setting must be suitably validated for purpose.
- Privacy and security-related risks include the potential disclosure of personally identifiable information through a breach of the DHT and end-user licensing agreements or attacks by bad actors. The EMA, for example, has highlighted compliance with applicable EU data protection requirements in light of the sensitive health data processed as of utmost importance. Innovators must also consider consumer protection-related issues in connection with terms of service that allow sharing of data with the DHT manufacturer or other third parties.
- While digital endpoints could help increase diversity in clinical trials, innovators must navigate the risks of bias inherent in the data and potentially in the inequitable use and deployment of DHTs themselves.
Innovators, whether those creating or investing in DHTs or considering deploying DHTs in their clinical trials, should continue to evaluate and optimize their use of digital endpoints to minimize these risks, including by conducting safety testing of the DHT and implementing safeguards designed to secure the data collected and transmitted by the DHT.
As digital endpoints continue to undergo evaluation, innovators are working towards a future in which these outcomes can replace traditional in-clinic endpoints in regulatory approval and clearance submission and regulation.
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