Note: This is Part 1 in a series of blog posts on developments from the U.S. Food and Drug Administration (“FDA”) regarding its commitments set forth under the Prescription Drug Under Fee Act Reauthorization Performance Goals and Clinical Trial Diversity and Modernization mandates established by Congress under the Food and Drug Omnibus Reform Act of 2022 (FDORA), including developments on the intersection and use of digital health technology in clinical trials and clinical trial diversity.
The Food and Drug Omnibus Reform Act of 2022 (FDORA) signed by President Biden on December 29, 2022, introduced significant changes to the way in which FDA will provide oversight for clinical trials as it pertains to “Clinical Trial Diversity and Modernization.” Under FDORA, among other things, FDA is required to issue guidance on decentralized clinical trials (which is a clinical trial in which some or all trial-related activities occur at a location separate from the investigator’s location) and to provide clarification on the use of digital health technologies (DHTs) in clinical trials.
Prior to the passage of FDORA, FDA set its sights on DHTs in the Prescription Drug User Fee Act (PDUFA) VII Commitment Letter, acknowledging the increased use of DHTs in drug development and the need for appropriate internal expertise and external guidance for their use and evaluation.
The Digital Health Technologies Framework
On March 23, 2023, FDA released the Framework for the Use of Digital Health Technologies in Drug and Biological Product Development (the DHT Framework) building on the PDUFA VII Commitment Letter in relation to the agency’s oversight of drug development and review of new drug registrations, label expansion, and safety monitoring. In the PDUFA VII Commitment Letter and the DHT Framework, FDA also sets forth a unifying definition for DHTs which are defined as “systems that use computing platforms, connectivity, software, and/or sensors for health care and related uses” (e.g., continuous glucose monitors, remote patient monitoring sensors).
FDA has increasingly focused on DHTs as their usage becomes more prevalent in clinical development and patient care. In December 2021, the draft guidance entitled Digital Health Technologies for Remote Data Acquisition in Clinical Investigations was issued to address the agency’s recommendations for the use of DHTs in clinical trials and how such technologies would be evaluated in marketing applications. More recently, in March, FDA issued the draft guidance Electronic Systems, Electronic Records, and Electronic Signatures in Clinical Investigations: Questions and Answers to provide recommendations to ensure such electronic systems, records and signatures used in clinical trials are trustworthy, reliable and equivalent to paper records and documentation that have traditionally been used in clinical investigations. The DHT Framework previews forthcoming guidance in Fiscal Year 2023, including draft guidance on decentralized clinical trials and considerations for prescription drug related software.
In support of fulfilling FDA’s PDUFA commitments around DHTs, the DHT Framework outlines a series of internal and external programs it will undertake. Planned internal programs include:
- Establishing a DHT Steering Committee with oversight of PDUFA commitment implementation;
- Training FDA personnel to enhance internal knowledge on DHTs;
- Ensuring consistency in evaluation of DHTs across agency review divisions;
- Assessment of statistical considerations for primary and secondary endpoint data; and
- Enhancing FDA’s IT capabilities to support the review, security and analysis of clinical data captured by DHTs.
In addition to current and future guidance, FDA’s external programs will involve:
- Meetings with clinical trial sponsors at various stages of product development;
- Support for the Drug Development Tool Qualification Program, which can be used to qualify DHTs for a “specific context of use,” and applied across multiple clinical trials; and
- Holding public meetings on various DHT related topics, including the recent virtual public meeting hosted by the Duke Margolis Center for Health Policy entitled Understanding Priorities for the Use of Digital Health Technologies to Support Clinical Trials for Drug Development and Review.
What’s On the Horizon
In these nascent stages of Congressional and FDA actions on clinical trial modernization, as indicated in the DHT Framework we anticipate further guidance and other feedback (e.g., through public meetings) on how FDA will review, assess and scrutinize DHTs as used during clinical development. Using DHTs and ensuring they are “fit for purpose” and continuing to maintain data integrity across clinical trials will be of utmost importance.
DHTs and decentralized clinical trials are also encouraged given their potential to increase access to diverse populations in clinical investigations. In considering whether to use DHTs in a clinical trial, however, sponsors will need to consider whether and what type of DHT is most sensible and if deploying the use of DHTs will truly capture the necessary endpoint data.
We will continue to monitor these and other insights from FDA in future final and draft guidance documents to come.
Considerations Beyond FDORA and FDA Regulations: Fraud and Abuse Implications
Changes to FDA law and regulation don’t happen in a vacuum, of course. The potential for fraud, waste, and abuse issues arising from clinical research arrangements has been a longstanding risk for the life sciences industry.
A key challenge we foresee for life sciences companies is maintaining a thoughtful approach to compliance with FDA clinical trial diversity requirements while remaining appropriately mindful of the fraud and abuse laws that overlay our healthcare system. Efforts to support clinical trial diversity through enhancements to technology to remove barriers from participation may raise concerns about potential “value” conferred among the parties involved in the study and may cause legal and compliance departments to pause when hearing new ideas involving DHT for clinical trials. Accordingly, clinical trial stakeholders may benefit from dual FDA compliance and fraud and abuse-focused risk assessments when considering incorporation of DHTs in clinical trials.
Key questions to help dig into the specifics of a scenario include:
- What, specifically, is the DHT and how is it regulated (device or non-device, or unclear)?
- Who are the planned users of the DHT?
- What is the purpose of the DHT (i.e., what is the DHT designed to do and what outcomes are expected from the use of the technology DHT)?
- What information will the DHT create, store, process or transmit?
- Who is going to pay for the DHT?
- Who will receive the DHT, and for what duration?
Reed Smith will continue to follow developments with regard to the DHT Framework, FDORA and FDA guidance, and their impact on best practices for incorporating DHTs in clinical trials. If you have questions on this topic, please reach out to the health care lawyers at Reed Smith LLP.