Spurred by the realities of the COVID-19 pandemic, FDA has taken a number of regulatory actions to advance the use of digital health technologies (“DHTs”) in clinical trials.  DHTs provide sponsors with opportunities to capture a broader array of information from study subjects than is typically available through traditional study designs.  This includes information from activities at home, work, school, outdoors, and while sleeping.  DHTs also enable the collection of data from a broader population, such as from those typically unable to report on their own experiences (e.g., infants and persons with cognitive impairments) or unable to travel to a study location.  At the same time, DHTs also present unique challenges.  For example, how do sponsors validate and verify data collected from such DHTs?  How do sponsors ensure the data are reliable?  How do sponsors alleviate disparities in access to DHTs?

On February 9, 2022, FDA held a webinar to provide clarity on a recently released draft guidance, Digital Health Technologies for Remote Data Acquisition in Clinical Investigations (“the Draft DHT Guidance”) published in December 2021.  This blog post outlines five key takeaways from the recent FDA webinar.

Background: FDA’s Draft DHT Guidance

FDA’s Draft DHT Guidance provides recommendations to facilitate the use of DHTs, particularly with respect to clinical trials.  FDA defines DHTs as systems that use computing platforms, connectivity, software, and/or sensors to collect data for healthcare and related uses.  FDA acknowledges that some DHTs qualify as devices under the Federal Food Drug & Cosmetic Act (“FDCA”), meaning they are subject to FDA oversight, but others do not.  Indeed, during the recent FDA webinar, agency staff confirmed that marketing authorization is not necessary in order to use a DHT in a clinical investigation.  Also, the Draft DHT Guidance clarifies that DHTs may include technologies that run on “general-purpose computing platforms”—defined as “commercial off-the-shelf computing platforms, with or without wireless connectivity, that may be handheld or otherwise portable in nature” (e.g., mobile phones, smartwatches, and tablets)—that are not generally regulated as devices.  Examples of DHTs include glucometers, software to measure mental acuity, and combinations of such technologies (e.g., a continuous glucose monitor device with a mobile application serving as the interface and providing analysis and alarm functions).

The Draft DHT Guidance provides helpful and detailed descriptions of the types of information to submit to FDA, as well as several examples of DHTs and how a sponsor might go about selecting a DHT that would be useful for a particular clinical investigation.  For example, the Draft DHT Guidance addresses how data acquired through DHTs can help with the evaluation of study endpoints and specifies information that should be contained in an application (e.g., an IND or IDE) for a clinical investigation in which the sponsor intends to use one or more DHTs, or in a marketing application (e.g., PMA, 510(k), de novo, or HDE) that includes such an investigation.  FDA also explicitly states that some of the considerations may be helpful for interactions with the Agency regarding uses of DHTs beyond acquiring data, such as clinical trial enrichment strategies (e.g., the prospective use of patient characteristics to select a desirable study population).

The Draft DHT Guidance describes how a DHT should be verified, validated, and assessed for usability in order to be deployed in a clinical trial.  Study sponsors also should ensure that any DHT sought to be employed in a clinical study is “fit-for-purpose,” i.e., that “the level of validation associated with the DHT is sufficient to support its use and interpretability” in the context of how it will be used in the clinical study (its “context of use”).  Verification and validation are related concepts that can be used to ensure that a DHT is fit-for-purpose for remote data collection in a clinical investigation.  In this context, “verification” refers to confirmation that the DHT is accurate and precise, and “validation” refers to confirmation that the DHT appropriately assesses the clinical event or characteristic in the proposed participant population.  Usability testing, on the other hand, should identify and address any potential errors or problems trial participants may experience when using the DHT.  During the webinar, FDA staff recognized the potential to conduct DHT validation studies in a variety of environments, including studies in the real world collecting real-world data from participants.

The Promise of DHTs

During the webinar, FDA staff reiterated the promise of DHTs to improve health and health outcomes as well as significantly improve clinical investigations by facilitating innovative, efficient, and/or more pragmatic clinical trial designs.  The presenters highlighted how DHTs provide the opportunity to observe the full patient population, building in diversity and health equity up front.  For example, DHTs can help open clinical investigations to underrepresented patient populations via remote data acquisition and decentralized clinical trials (i.e., where some or all of the trial-related activities occur at a location separate from that of the investigator).  In addition to expanding the reach of the patient pool, this also alleviates the burden on patients of traveling to a trial site during working hours.  FDA cautions, however, that sponsors should consider ways they may need to adapt DHTs to allow for the inclusion of diverse populations (e.g., providing translated versions, ensuring DHTs reliably collect data from healthy participants as well as participants of interest, considering usability and access, etc.).  Additionally, sponsors may need to consider ways to alleviate disparities in access to DHTs (e.g., cost considerations, use of personal DHTs versus trial-provided DHTs, etc.).  For example, a 2021 bill introduced by Rep. Ruiz, titled the DIVERSE Trials Act, would confirm that the free provision of DHTs by drug or device manufacturers to their clinical trial participants would not be considered a violation of certain laws if the use of DHTs would facilitate the diversity of patient populations.

Five Key Takeaways from the FDA Webinar

  1. FDA’s recommendations for verification and validation of the DHT apply regardless of whether the DHT meets the definition of a device under the FDCA. In other words, sponsors need to ensure that all DHTs used in clinical trials—even non-device DHTs—are verified, validated, and assessed for usability.  That being said, FDA staff clarified during the webinar that only DHTs that meet the definition of a device and are intended to be used in a clinical trial are subject to 21 C.F.R. part 812 (regulations related to the use of investigational devices).  When asked during the webinar whether there were advantages of using a device DHT versus a non-device DHT in a clinical trial, FDA staff replied that it depends on the needs of the investigation and the intended use of the product.  For example, if the investigation requires glucose measurements, a review board would likely pause and have questions about the use of a DHT glucometer (typically a medical device) that has not been cleared by FDA’s Center for Devices and Radiological Health (“CDRH”).  FDA staff further confirmed that cleared devices reviewed by CDRH are a “good measure” of data, but that marketing authorization alone is not sufficient to show a DHT is fit-for-use.
  2. Most regulatory requirements for devices, including premarket clearance or approval, do not apply to DHTs intended for use in clinical investigations if the clinical investigation complies with applicable requirements under 21 C.F.R. part 812, but sponsors may have other obligations when they employ DHTs that are devices. For example, if a sponsor undertakes any clinical verification or validation testing of a DHT that qualifies as a device under the FDCA, that testing may itself constitute a clinical investigation subject to applicable investigational device regulations (i.e., 21 C.F.R. parts 50, 56, and/or 812).  Additionally, if a DHT used in an investigation qualifies as a significant risk device under 21 C.F.R. § 812.3(m), the sponsor would be required to submit an IDE to FDA for the same investigation.  During the webinar, FDA staff cautioned that DHTs also intended for use outside of a clinical investigation should be treated just like any other device intended for market, including that Medical Device Reporting obligations under 21 CFR part 803 could be triggered if a device DHT malfunctions or causes a death or serious injury.
  3. FDA encourages external collaboration and recycling to rapidly advance and multiply the use of DHTs. During the webinar, FDA recommended sponsors involve DHT manufacturers, patients, caregivers, regulators, and other stakeholders in validation steps to ensure the product is fit-for-purpose.  FDA also emphasized that sponsors should leverage data that may be available from multiple sources, such as marketing applications or data from the DHT manufacturer, to support their submissions and fit-for-purpose arguments.  FDA presenters also encouraged sponsors to make use of voluntary qualification programs to allow for reliance on DHTs in multiple clinical investigations for different premarket submissions.  For example, although the Draft DHT Guidance recommends that study sponsors ensure that DHTs employed in a particular clinical trial are fit-for-purpose, the Agency notes that the multiple mechanisms exist by which DHTs may be pre-qualified for contexts of use, including qualification as a “Drug/Medical Device Development Tool.”  For DHTs that are outside the scope of the DDT qualification programs but still present a potential benefit for drug development, FDA suggests that sponsors and other stakeholders consider submitting DHT-related proposals to the Innovative Science and Technology Approaches for New Drugs (“ISTAND”) Pilot Program.  In short, one of FDA’s aims appears to be around fostering collaboration and wide use of DHTs.
  4. Novel endpoints driven by new insights that were not previously measurable before DHTs should be developed as in any other instance. When a DHT will simply replicate an existing endpoint, however, a new justification will generally not be expected (although validation of the new method to measure the endpoint should still be provided).  In any event, FDA staff clarified that sponsors may leverage existing data for future clinical trials and need not repeat evidence generation.  FDA staff also noted they look forward to making available examples of digital endpoints as they become public.
  5. Consult FDA early and often. During the webinar, FDA staff repeatedly encouraged sponsors to engage with FDA and early and often when considering using DHTs in a clinical trial.  FDA staff emphasized that the earlier sponsors can obtain feedback, the better.  FDA also recommended sponsors make use of FDA guidance documents and additional mechanisms (such as the voluntary programs described above) to receive clarity on whether a proposed DHT would be appropriate for any particular trial.

FDA staff expressed that they look forward to receiving input on the Draft DHT Guidance to inform their next steps.  Comments regarding the Draft DHT Guidance are due by March 22, 2022.

Photo of A.J. Carvalho A.J. Carvalho

A.J. Carvalho is an associate in the Washington office, where he practices in the Patent Litigation, False Claims Act, and White Collar Defense and Investigations Practice Groups, and also maintains an active pro bono practice.

Prior to attending law school, A.J. worked at…

A.J. Carvalho is an associate in the Washington office, where he practices in the Patent Litigation, False Claims Act, and White Collar Defense and Investigations Practice Groups, and also maintains an active pro bono practice.

Prior to attending law school, A.J. worked at Walter Reed National Military Medical Center coordinating exploratory clinical research studies related to blast injuries, particularly amputation, and concomitant conditions.

Photo of Olivia Dworkin Olivia Dworkin

Olivia Dworkin minimizes regulatory and litigation risks for clients in the medical device, pharmaceutical, biotechnology, eCommerce, and digital health industries through strategic advice on complex FDA issues, helping to bring innovative products to market while ensuring regulatory compliance. With a focus on cutting-edge…

Olivia Dworkin minimizes regulatory and litigation risks for clients in the medical device, pharmaceutical, biotechnology, eCommerce, and digital health industries through strategic advice on complex FDA issues, helping to bring innovative products to market while ensuring regulatory compliance. With a focus on cutting-edge medical technologies and digital health products and services, Olivia regularly helps new and established companies navigate a variety of state and federal regulatory, legislative, and compliance matters throughout the total product lifecycle. She has experience counseling clients on the development, FDA regulatory classification, and commercialization of digital health tools, including clinical decision support software, mobile medical applications, general wellness products, medical device data systems, administrative support software, and products that incorporate artificial intelligence, machine learning, and other emerging technologies.

Olivia also assists clients in advocating for legislative and regulatory policies that will support innovation and the safe deployment of digital health tools, including by drafting comments on proposed legislation, frameworks, whitepapers, and guidance documents. Olivia keeps close to the evolving regulatory landscape and is a frequent contributor to Covington’s Digital Health blog. Her work also has been featured in the Journal of Robotics, Artificial Intelligence & Law, Law360, and the Michigan Journal of Law and Mobility.