The term “digital endpoints” is often used to describe clinical trial endpoints that use sensors such as microphones in smartphones, wearable devices, and digital pills to enable more frequent and objective remote monitoring of patients during clinical trials. clinical tests. In light of the recent increased interest in these new endpoints, regulators, innovators and investors should be aware of key global trends with respect to the development and use of these endpoints, as well as the clinical risks, privacy, cybersecurity and other related legal aspects. risks.
What are digital terminals?
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 has a clinically significant effect. The National Medical Products Administration (NMPA) in China, the Pharmaceuticals and Medical Devices Agency (PMDA) in Japan, the Medicines and Health Products Regulatory Agency (MHRA) in the United Kingdom and the The European Medicines Agency (EMA) in the EU similarly assesses the effectiveness of a medicine for its approval. In order to present evidence of a drug’s effectiveness, the manufacturer provides data on endpoints, which are measurable outcomes used to achieve the goals of a clinical trial.
Digital endpoints are a new type of endpoint. These parameters are assessed using sensor-generated data that is often collected outside of a clinical setting, such as in a patient’s daily activities. Digital terminals can capture a 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 taking existing measures in new ways, while also allowing registration of new measures that were not previously accessible. Rather than relying on subjective assessments of participant progress during 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, especially for people with physical or cognitive limitations or time constraints. This, in turn, allows manufacturers to open up clinical trials to a more diverse and representative population hitherto underrepresented in clinical research. This is partly due to the frequency of study visits required and other resource constraints. The use of digital endpoints in clinical trials can alleviate some of these burdens.
Current regulatory landscape affecting digital devices
Numerical endpoints have not yet been accepted to support new drug approvals in the United States. However, in December 2021, the FDA released draft guidance providing its recommendations on the use of digital health data acquisition in clinical investigations, noting that regulatory acceptance of digital endpoints in support of drug approvals can happen in the short term.
Outside of the United States, there appears to be global regulatory consensus on the use of digital terminals, or at least digital tools, in clinical trials:
- China’s NMPA has released guidelines on managing clinical trials, explaining that sponsors can use digital technology to remotely manage clinical trials.
- Japan’s PMDA also recommended that sponsors find alternative approaches to maintaining trial participation during the Covid-19 pandemic, such as remote monitoring.
- The landscape of clinical trials in the UK is currently changing post-Brexit, with new rules expected soon. However, the MHRA recently recognized that real-world data collected by the technology can play a role in clinical studies and randomized controlled trials, including in relation to regulatory decisions about the design of clinical trials.
- The EU EMA has published guidance on the qualification of digital technology-based methodologies to support drug approval, and draft guidance on electronic systems and electronic data in clinical trials is underway drafted by the working group of good clinical practice inspectors.
Regulators have also worked with the industry to help advance acceptance of digital terminals. The Digital Medicine Society and its partners at 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 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 terminals
As they develop digital terminals, innovators consider associated risks to trial participants, including clinical, privacy, and security risks:
- A key clinical risk is that participants could be physically affected by the characteristics of digital health technology (DHT) used to measure digital parameters, for example, components in contact with the skin. Another clinical risk could be presented by the collection of erroneous or incomplete data by DHT, either due to lack of participant compliance or technology-related issues. The MHRA, for example, has stressed the importance of strong data regardless of its source, and that any tool, including DHT, used in a trial setting must be properly validated for its purpose.
- Privacy and security risks include potential disclosure of personally identifiable information through violation of DHT and end user license agreements or attacks by bad actors. The EMA, for example, highlighted compliance with applicable EU data protection requirements in light of sensitive health data being handled as being of utmost importance. Innovators should also consider consumer protection issues in relation to terms of service that allow data sharing with manufacturer DHT or other third parties.
- While digital endpoints could help increase the diversity of clinical trials, innovators must manage the risks of bias inherent in the data and potentially inequitable use and deployment of DHTs themselves.
Innovators, whether they are creating or investing in DHT or considering deploying DHT in their clinical trials, should continue to evaluate and optimize their use of digital devices to minimize these risks, including conducting DHT safety testing. and implementing safeguards designed to secure the data. collected and transmitted by the DHT.
As digital endpoints continue to be evaluated, innovators are working toward a future in which these outcomes can replace traditional in-clinic endpoints in regulatory approval and licensing submission and regulation.
Photo: exdez, Getty Images