FDA issues final guidance on digital health technologies for data acquisition in clinical investigations

On December 21, 2023, FDA issued a final guidance on the use of digital health technologies (DHTs) in data acquisition for clinical research. The new guidance builds on a 2021 draft guidance and offers FDA’s latest thinking on the interaction between device regulations and expectations for DHTs in clinical research contexts, new details on how to validate the use of particular DHTs, and additional information on the Agency’s expectations in relation to records retention and inspections.

The guidance outlines recommendations intended to facilitate the use of DHTs in clinical investigations for the evaluation of medical products. These recommendations cover:

1. Selection of DHTs that are suitable for use in clinical investigations
2. Description of DHTs in regulatory submissions
3. Verification and validation of DHTs for use in clinical investigations
4. Use of DHTs to collect data for trial endpoints
5. Identification and management of risks associated with the use of DHTs during clinical investigations
6. Retention and protection of data collected by DHTs, and
7. Roles of sponsors and investigators related to the use of DHTs in clinical investigations.

The guidance does not address whether a DHT is a regulated device, nor does it cover clinical outcome assessments (COAs).

Background on DHT policy

FDA defines a DHT as “a system that uses computing platforms, connectivity, software, and/or sensors, for health care and related uses.” These technologies, particularly sensor-based or wearable technologies capable of remotely collecting patient data, have rapidly become valuable research tools. Studies employing DHTs and decentralized trial designs allow for new data capture in new settings and hold the promise of broadening research participation to populations who have had difficulty accessing more traditional clinic-centric research.

COVID-19-era upheaval prompted industry and regulatory bodies to explore avenues for updating the conventional clinical research paradigm. This has involved rethinking trial designs and participant engagement strategies with a focus on achieving equitable representation. In this context, DHTs are generally seen as valuable tools.

DHTs could be used to include underrepresented and diverse populations by facilitating decentralized clinical trials. They have the potential to obtain data about signs (eg, scratching, sleep patterns) from infants or participants who are cognitively impaired and may not be able to report symptoms such as itching or insomnia.

In late 2021, FDA issued its inaugural draft guidance on DHTs for remote data acquisition. The draft clearly conveyed FDA’s desire to ensure that the data derived from DHT-based methods truly reflects what researchers intend to measure and remains relevant to the desired outcome of interest (ie, verification and validation of DHTs). The draft guidance raised significant questions around qualifying a DHT for specific uses, navigating the interplay between the guidance, medical device regulations, and the level of detail of DHT-derived data required for marketing submissions.

In issuing this final guidance, FDA has met the Food and Drug Omnibus Reform Act (FDORA) mandate to update DHT guidance by the end of 2023 and has attempted to answer some of the outstanding questions surrounding DHTs.

DHT final guidance

The final guidance captures many of the points outlined in the draft guidance, but incorporates some noteworthy changes:

Scope

• The updated introduction section dives deeper into what a DHT encompasses and its potential applications. In line with recent statements from FDA that the Agency is taking a broad view on what constitutes a DHT, the final guidance clarifies that DHTs encompass wearables and software applications like mobile apps.
• Similar to FDA’s approach to software products, an important clarification emphasizes that a DHT is defined by its function. Like devices, a DHT can have multiple functions, and each function should be assessed for device functionality.
• The guidance extends beyond investigational new drug (IND), investigational device exemption (IDE), and marketing applications to include submissions related to drug/device development tool (DDT/MDDT) submissions. Some of the considerations in the final guidance “may be helpful for other uses of DHTs, such as the screening and selection of trial participants and the enrichment of trial populations”.
• While the final guidance primarily focuses on DHTs intended for remote data acquisition, it acknowledges applicability even when DHTs are used by trial participants at a trial site (eg, data capture by digital devices that might occur both in and outside of clinic visits).

Interaction between device regulations and DHT expectations

• The final guidance clarifies that, in the (unlikely) scenario in which both an IND and IDE would technically be required, the Agency does not generally expect both to be filed. The expectation is that sponsors could submit an IND only, where it would reflect the same information that would also be available in an IDE.
• Additionally, DHTs that integrate an uncleared device function, approved or permitted under an IDE, would likely not need to meet design control requirements, provided they undergo appropriate validation and verification in line with guidance recommendations.

Using DHTs in clinical investigations

• A new section on technical and performance specifications emphasizes the need to identify DHTs and technologies meeting these standards which can be considered “fit-for-purpose” – for example, the specifications of smartphone cameras that could be needed for certain readings.
• Additionally, the guidance streamlined the bring-your-own-device (BYOD) section, acknowledging the pros and cons of a BYOD approach and making it clear that participants lacking access to specific devices should not be excluded from participation.

Verification, validation, and usability

• FDA continues to refer to key points of the verification and validation process which were identified in the draft guidance. These include methods to compare DHT measurements to reference measurements and identifying factors that impact measurement and evaluating calibration processes. The final guidance adds two new factors: i) confirming that measurements across different makes/models of DHT products are consistent, where different products are to be used, and ii) evaluating the potential differences in remote and in-clinic data capture using the same DHTs.
• The final guidance provides higher-level commentary than the draft in regard to usability evaluations. It recommends assessing participants' proficiency in using DHTs remotely and highlights the importance of these evaluations to ensure accurate measurements and sustained participant engagement.

Statistical analysis and records

• The final guidance expands on statistical analysis and trial design considerations, offering additional insights for sponsors when designing studies and drafting statistical analysis plans.
• The guidance clarifies FDA’s inspection approach, indicating that the Agency does not intend to request machine or raw data that requires electronic processing in order to be understood. Further, FDA does not intend to inspect individual DHTs for source data when all data, including metadata, captured by the DHT are securely retained in a durable electronic repository in accordance with a sponsor’s prespecified plan.
• The final guidance discusses how FDA regulations for clinical investigation records apply to investigations using DHTs. It refers to the draft guidance titled, “Electronic Systems, Electronic Records, and Electronic Signatures in Clinical Investigations: Questions and Answers” (March 2023), which provides greater detail on issues pertaining to access controls, audit trails, data sources, and inspections specific to investigations using DHTs.

Sponsor, investigator, and training

• The final guidance introduces the concept of end-of-study closeout procedures, which sponsors are responsible for developing in relation to DHT studies, along with the technical assistance plans and risk management plans, as mentioned in the draft.
• Generally, FDA does not expect investigators to monitor DHT data continuously, but there may be circumstances in which this is clinically necessary. This should be addressed in the safety monitoring plan.
• Investigators play a pivotal role in ensuring participants understand DHTs and their implications, including delivering sponsor-developed training. Notably, the final guidance clarifies that participant training should include a confirmation that use of the DHT will be restricted to the trial participants and/or caregivers, in an effort to ensure the validity of DHT-derived data.

Future developments

DHT regulation is a developing area, with FDA set to host a variety of workshops on DHTs over the next few years under the Prescription Drug User Free Act (PDUFA) VII commitments. FDA’s recently established DHT Advisory Committee is also expected to weigh in on outstanding questions and DHT policy development. While the latest guidance is final, updates should be expected.

To find out more about the implications of the final guidance for your business, please contact any of the authors.