Last month, the Food and Drug Administration (FDA) announced the publication of the “Framework for the Use of Digital Health Technologies in Drug and Biological Product Development” (Framework) by the Center for Drug Evaluation and Research (CDER) and the Center for Biologics Evaluation and Research (CBER). The publication of this digital health technology (DHT) framework fulfills an FDA commitment under the seventh iteration of the Prescription Drug User Fee Act reauthorization (PDUFA VII).
What Are DHTs?
In the context of the Framework, DHTs are “systems that use computing platforms, connectivity, software, and/or sensors for health care and related uses.” This includes technologies intended for use as a medical product, in a medical product, or as an adjunct to other medical products (i.e., drugs, devices and biologics). DHTs can be in the form of hardware (e.g., sensors for recording of physiological and/or behavioral data), software (e.g., mobile phone, smart watch), or a combination of both hardware and software (e.g., continuous glucose monitoring device with sensor and mobile application). DHTs may be used to support more efficient drug development and uses include increasing decentralization of trial-related activities (e.g., promoting increased trial diversity and retention of study participants), facilitating direct collection of information from patients, and allowing for development of novel endpoints that can help paint a more detailed picture of how participants feel and function in their daily lives.
The Framework describes the multifaceted approach FDA intends to use to address how DHTs can be used to support drug development and regulatory decision-making, including workshops and demonstration projects, stakeholder engagement, establishment of internal processes to support evaluation of DHTs for use in drug development, and publication of guidance documents. The Framework itself is “not a guidance document and does not propose or establish policies.”
Some of the significant issues addressed in the framework include:
DHT Steering Committee – FDA established the DHT Steering Committee to develop internal programs to build review capacity and expertise and to ensure consistent review policies for the use of DHTs in drug development. The Committee has overseen the design of the Framework, and consists of senior staff from CDER, CBER, and the Center for Devices and Radiological Health, as well as the Oncology Center of Excellence and the Office of Clinical Policy and Programs. Committee activities will include:
- Gathering information on the present state of DHTs
- Making policy recommendations on the use and evaluation of DHT-based measurements in drug development
- Overseeing and coordinating DHT-related drug development working groups
- Engaging with external stakeholders on DHT-related issues in drug development
Technical Expertise and Training – FDA will “build on its technical expertise and develop training within the human drugs and biological products programs to enhance internal knowledge regarding the use of DHTs in drug development.” Areas of focus include: verification and validation, use of a participant’s own DHT or general-purpose computing platform, upgrades and updates of DHTs in drug development, artificial intelligence and machine learning, and technical consultation of experts and staff training.
Consistency of Evaluations Across Review Divisions – “A single DHT measurement may be used for studies of different diseases and different drugs.” Review divisions and centers in the FDA should have consistent approaches to the review and evaluation of submissions that contain DHT-related data, and the Steering Committee is tasked with facilitating consistent approaches.
Statistical Considerations in the Analysis of DHT-Derived Data – The use of DHT-derived endpoints presents “unique statistical considerations” for FDA related to data quality, technical data specifications, provenance, techniques, and algorithms used for processing, summarizing, and analyzing DHT data, and treatment of missing data during its reviews. Existing and novel statistical methods of validation of DHT-derived data must be assessed, and FDA states it will “consider developing technical data specifications to facilitate submission of readily analyzable DHT-derived data supporting drug development.”
IT Capabilities – FDA anticipates “new challenges” with the “ability to receive and analyze large DHT-generated datasets to support a regulatory decision.” FDA will enhance its IT capabilities to support the review of such, including development of internal systems to monitor trends in submissions containing DHT-related data and establishment of a secure cloud technology to enhance infrastructure and analytics. After establishing the cloud, FDA will pilot a secure, cloud-based mechanism to support submission and review of DHT-generated datasets.
FDA Meetings with Sponsors – FDA engagement with sponsors regarding the use of DHTs may occur at different stages of drug development, including pre-submission meetings, pre-IND meetings, IND and NDA review meetings, and other meetings and communications.
Drug Development Tool Qualification Program – “FDA has qualification programs that are intended to support the development of tools for use in assessing medical products and that provide another avenue for sponsors and other stakeholders to engage with the Agency.” DHT developers may choose to pursue qualification of DHTs as drug development tools for a specific use, and a qualified DHT may be relied upon in multiple clinical investigations to support premarket drug submissions where the context of use is the same without having to repeat studies to support qualification.
Guidance – To facilitate the appropriate use of DHTs in drug development, FDA has published various draft guidances, including the following:
- Digital Health Technologies for Remote Data Acquisition in Clinical Investigations (Dec. 2021)
- Electronic Systems, Electronic Records, and Electronic Signatures in Clinical Investigations: Questions and Answers (Mar. 2023)
FDA plans to develop additional guidance in identified areas of need informed by stakeholder engagement and plans to publish the following draft guidance in 2023:
- Decentralized Clinical Trials for Drugs, Biological Products, and Devices (planned for 2023)
- Regulatory Considerations for Prescription Drug Use-Related Software (planned for publication by end of 2023)
Public Meetings – By Q2 2023 FDA will convene the first of a series of five public meetings or workshops with key stakeholders to gather input on issues related to the use of DHTs in regulatory decision-making for drug and biological product development. The first meeting is March 28–29, 2023 on Understanding Priorities for the Development of Digital Health Technologies to Support Clinical Trials for Drug Development and Review. Other meetings will be designed to address the following topics:
- Identifying approaches to DHT verification and validation
- Understanding DHT data processing and analysis to inform the need for novel analytical techniques
- Addressing the regulatory acceptance of safety monitoring tools that utilize AI/ML-based algorithms for pharmacovigilance purposes
- Understanding emerging issues
Demonstration Projects – “FDA will identify at least 3 issue-focused demonstration projects to inform methodologies for efficient DHT evaluation in drug development.” These projects may involve engagement with researchers, patient groups, and other stakeholders and will cover key issues to inform regulatory policy development and provide regulatory advice.
External Organizations – FDA has participated in several forums addressing the use of DHTs in drug development and will continue to engage with external organizations to facilitate meeting the objectives discussed above.
Comments on the Framework must be submitted by May 23, 2023. MoFo is continuously monitoring these developments. Please reach out to MoFo’s FDA + Healthcare Regulatory and Compliance practice for a more detailed analysis and discussion of the implications of these developments.
Because of the generality of this update, the information provided herein may not be applicable in all situations and should not be acted upon without specific legal advice based on particular situations.