The publication of the framework fulfils an FDA commitment under the Prescription Drug User Fee Act VII to establish a framework to further guide the use of data derived from the use of DHTs to support drug development and review.³ In addition to an overview of the general regulatory background for the use of DHTs and the current DHT landscape, the framework goes into detail regarding how to address certain challenges related to the use of DHTs in regulatory decision-making. Notably, FDA acknowledges that DHTs may incorporate the use of AI (artificial intelligence) algorithms, and the agency intends to build on its domain-specific expertise in data science, informatics, statistics, and mathematics to help ensure the appropriate application of AI technology in the context of DHTs for drug development. The guidance also includes proposals to support activities related to DHTs within FDA (internal programs) and proposals to engage industry and other stakeholders regarding DHT use and development (external programs).

Stakeholders may submit comments regarding the proposed framework to FDA until 23 May 2023.

In more detail

As defined in the proposed framework, "DHTs are systems that use computing platforms, connectivity, software, and/or sensors for health care and related uses." They may be in hardware or software form and "often consist of sensor hardware that allows for continuous or intermittent recording of physiological and/or behavioral data (e.g., blood pressure, physical activity, glucose levels). A DHT may also consist of a software application run on a general-purposes computing platform, such as a smart watch. DHTs are currently playing an important role in clinical research, including for continuous data collection and remote collection of data. Use of DHTs may alleviate the burden on trial participants to travel to a site, provide the opportunity to directly collect data from trial participants, and facilitate collection from participants who are unable to report their experiences, such as those with cognitive disabilities.

Below we summarize FDA's proposal to establish programs to support activities related to DHTs to further drug development and review, including the establishment of both internal and external programs to support such activities.

DHT Steering Committee

The framework proposes to establish a DHT Steering Committee consisting of various members of senior staff across a number of FDA centers. In addition to helping to oversee the design of the regulatory framework and serving as a guiding body on activities related to DHT development, the steering committee will serve as a forum to share information and communications about DHTs used in drug development. The committee will also enhance consistency across FDA regarding use of DHTs in regulatory decision-making by providing recommendations across FDA centers regarding DHTs, including facilitating consistent approaches to the review and evaluation of drug submissions.

Technical Expertise and Training

As part of the framework to develop internal support programs, FDA proposes to enhance consistency across centers with regard to use, development and review of DHTs by building technical expertise in certain topics related to DHTs, including the following:

• Verification and validation processes to ensure DHTs are accurate and reliable
• Use of personal DHTs (i.e., a participant's own DHT) or general-purpose computing platform
• Upgrades and updates of DHTs in drug development, including understanding the impact of updates or modifications to existing DHTs
• Artificial intelligence and machine learning, including enhancing domain-specific expertise in data science, informatics, statistics, and mathematics to ensure AI technology is applied appropriately in the DHT context

FDA also proposes to increase review capacity and enhance staff training. The agency will leverage its statistical expertise to address analytical challenges and considerations for endpoints derived from DHT data and enhance IT capabilities that go to supporting the review of data derived from DHTs.

External Programs

In furtherance of developing external programs to support activities relating to DHTs, the framework includes a description of a number of programs to engage key external stakeholders to help FDA better understand opportunities and challenges associated with DHTs. The framework proposes that FDA can gather input by holding workshops or public meetings with key stakeholders and includes a proposal that FDA convene the first of a series of five public meetings or workshops by the end of the second quarter of FY2023. FDA will also identify at least three demonstration projects to inform methodologies for the efficient evaluation of DHTs in drug development.

The framework also recognizes that engagement between sponsors and FDA during the different stages of drug development may also occur frequently and may include meetings with the DHT Steering Committee. Such meetings include pre-IND meetings, pre-submission meetings, IND and NDA review meetings, Critical Path Innovation Meetings, and other meetings and communications related to the drug development. The meetings will provide an opportunity for sponsors and FDA to discuss important regulatory considerations, such as development of trial endpoints.

The proposed framework references FDA's qualification program, which sponsors and stakeholders may choose to pursue to qualify DHTs as drug development tools for a specific context of use. FDA also lists a number of draft guidance documents related to the use of DHTs that, when finalized, will reflect the agency's current thinking related to the topics, and notes that FDA plans to develop additional guidance documents covering the use of DHTs.

Key takeaways

• The use of DHTs has accelerated in recent years, especially with the onset of the COVID-19 pandemic. In line with FDA's proposed framework, we anticipate seeing efforts to enhance and improve agency review of submissions containing data derived from DHTs.
• Because the framework is new, and the agency's review will be evolving, we recommend being vigilant in staying up-to-date on FDA's latest guidance if using DHTs in clinical research or making a submission to the agency with data derived from DHTs.
• As noted in FDA's proposed framework, using DHTs may involve the use of AI, and also increase data privacy and confidentiality concerns. We recommend considering these areas and ensuring compliance with applicable privacy laws when using DHTs.

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For further information and to discuss what this development might mean for you, please get in touch with the Baker McKenzie contacts provided above.

1 Digital Health Technologies for Remote Data Acquisition in Clinical Investigations, available at (https://www.fda.gov/media/155022/download).

2 Electronic Systems, Electronic Records, and Electronic Signatures in Clinical Investigations: Questions and Answers, available at (https://www.fda.gov/media/166215/download).

3 PDUFA Reauthorization Performance Goals and Procedures Fiscal Years 2023 through 2027, p.65, available at (https://www.fda.gov/media/151712/download); Digital Health Technologies (DHTs) for Drug Development (23 March 2023), available at (https://www.fda.gov/science-research/science-and-research-special-topics/digital-health-technologies-dhts-drug-development).