This month, the U.S. Food and Drug Administration (FDA) released its Framework for the use of digital health technologies (DHTs) in drug and biological product development. This Framework is part of the FDA’s ongoing effort to support the increased use of DHTs for new drug applications, biologics license applications, supplements to those applications, and drug safety monitoring. DHTs include technologies such as wearable, implantable, ingestible, and environmental sensors, and software applications on mobile phones, among others. Advances in sensor technology, general-purpose computing platforms, and methods for data capture, transmission, and storage have revolutionized the ability to remotely obtain and analyze clinically relevant information from individuals. DHTs used for remote data acquisition are playing a growing role in healthcare and offer important opportunities in clinical research. DHTs can support traditional site-based clinical trials and enable the conduct of decentralized clinical trials, which are clinical investigations where some or all trial-related activities occur at locations other than traditional clinical trial sites.

The Framework includes the FDA’s plans for internal and external actions that the agency will perform to facilitate use of DHTs in regulatory decision making as part of the FDA’s commitments outlined in the Prescription Drug User Fee Act VII (PDUFA VII). These activities include: 1) publishing a framework for the use of DHTs in drug and biological product development; 2) establishing a DHT Steering Committee; 3) convening public meetings; and 4) identifying demonstration projects.

Internal Actions

The FDA has created a DHT Steering Committee (the Committee).

The Committee is composed of senior staff from Center for Drug Evaluation and Research (CDER), Center for Biologics Evaluation and Research (CBER), and Center for Devices and Radiological Health (CDRH). The Committee will oversee the implementation of the PDUFA VII commitments related to evaluating DHT-based measurements in human drug development; serve as the guiding body on activities and policy development related to DHTs; and serve as a forum for shared communication about DHT use in drug development. The Committee will also help facilitate consistent approaches to the review and evaluation of submissions that contain DHT-related data.

The FDA plans to expand its technical expertise and training for staff.

The FDA plans to focus on increasing technical training and expertise in:

1. Assessment of DHT validation and verification. Building out the FDA’s internal expertise in statistics, mathematics and general-purpose computing platforms will help ensure to ensure that DHTs are accurate, reliable, and meet the intended user’s needs.
2. General purpose computing platforms to address participants’ use of their own DHTs in clinical investigation. The FDA is interested in creating minimal technical and performance specifications to ensure that measurements are consistent across different protocol specific DHTs.
3. Understanding the impact of updates or changes to DHTs during clinical investigations. During clinical investigations new models of DHTs may become available or require software updates. The FDA seeks to collaborate across Centers to determine if there is a meaningful difference in results observed before and after the updates to a DHT and how the differences impact interpretability of clinical investigation results.
4. Data science, informatics, statistics, and mathematics to ensure the appropriate application of Artificial Intelligence (AI) technology in the context of DHTs used for drug development. DHTs may be incorporated using AI algorithms into drug development, and the FDA wants to build out the technical expertise to ensure AI-mediated incorporation is appropriate.

The FDA plans to expand scope of analysis of DHT-derived data and the FDA’s IT capabilities.

The FDA will use its current statistical expertise to address novel considerations for clinical endpoints derived from DHT data and potentially develop technical data specifications to facilitate the submission of DHT data supporting drug development. To facilitate review of DHT-related submissions, the FDA plans to enhance its internal systems, including establishing secure cloud technology to enable the agency to effectively receive, aggregate, store, and process large volumes of data from drug trials conducted using DHTs. CDER and CBER will also likely request applicants identify submissions that contain information related to the use of DHTs, and the Centers will work together to promote the development and adoption of data standards for DHT-generated datasets.

External Programs

As part of their external facing actions, the FDA plans to hold meetings with sponsors, review requests for a DHT to be qualified as a drug development tool through their preexisting qualification program, hold public meetings, provide demonstration projects, engage with external organizations, and publish guidance documents that reflect the FDA’s thinking on DHTs topics.

The FDA’s planned public meetings will cover five distinct topics: 1) priorities for the development of DHTs to support clinical investigations; 2) approaches to DHT verification and validation; 3) DHT data processing and analysis; 4) regulatory acceptance of safety monitoring tools that utilize AI and ML-based algorithms for pharmacovigilance purposes; and 5) emerging issues.

The FDA has already published two draft guidance documents that 1) provide recommendations to address which information should be contained in an investigational new drug application (IND) or an investigational device exemption (IDE) application for a clinical investigation in which the sponsor plans to use one or more DHTs or in a marketing application; and 2) address stakeholder questions about the use of electronic systems, electronic records, and electronic signatures in clinical investigations of medical products, foods, tobacco products, and new animal drugs: “Digital Health Technologies for Remote Data Acquisition in Clinical Investigations (December 2021)” and “Electronic Systems, Electronic Records, and Electronic Signatures in Clinical Investigations: Questions and Answers (March 2023).” The FDA also plans to publish two additional guidances in 2023 addressing regulatory considerations for prescription drug use-related software and decentralized clinical trials for drugs, biological products, and devices.

DHTs have the potential to reduce the burden on trial participants, ultimately leading to improved trial recruitment rates, better participant retention over longer periods of time, and increased participant diversity. DHTs may also facilitate the collection of data: 1) while participants perform daily activities and 2) directly from trial participants who are unable to report their experiences—for example, due to cognitive impairment. These features may provide a broader picture of how participants feel or function in their daily lives but would otherwise be unavailable or impractical without the use of DHTs.

Nevertheless, certain issues must be addressed to successfully implement DHTs into regulatory decision making. These issues include among others the clinical meaning and significance of measurements to patients, caregivers, and healthcare providers as well as data privacy and confidentiality concerns.

For more information, please contact James Ravitz, Georgia Ravitz, Eva Yin, Paul Gadiock, Shawn Lichaa, or any member of the firm’s FDA regulatory, healthcare, and consumer products practice.

Alex DeLaney and Paul Gadiock contributed to the preparation of this Wilson Sonsini Alert.