New FDA Draft Guidance on the Use of Digital Health Technologies in Clinical Trials | Bass, Berry & Sims PLC
On December 23, 2021, the United States Food and Drug Administration (FDA) announced the availability of a draft guidance for industry, investigators, and other stakeholders titled “Digital Health Technologies for Acquisition remote data in clinical investigations ”(referral). The guide synthesizes FDA recommendations, based on feedback solicited from numerous stakeholders over the past six years. Once finalized, the guide will directly affect pharmaceutical, device, and biotech companies, as well as research institutes, which sponsor FDA-regulated clinical investigations incorporating digital health technologies (when used for medical purposes). related to health care, “DHT” as defined in the guide). It will also affect investigators, research sites, and Institutional Review Boards (IRBs) that conduct or review these clinical investigations. The FDA accepts comments on the Guide until March 23, 2022.
Context and Applicability
Sensors, applications, internet-connected medical devices, computing platforms and similar technologies are widely deployed in clinical trials today. Their uses range from simple reminders or engagements for largely in-person trials to data collection for endpoint evaluation in decentralized clinical trials. DHTs provide opportunities to record richer data than would otherwise be available, facilitate direct and continuous collection of information from participants who are unable to report their experiences (for example, young children and people with dementia), improve study adherence and retention, and help improve equity in the availability of clinical trials. They also raise issues for clinical trial sponsors, investigators, and IRBs who interpret FDA regulations written in a largely pre-DHT world.
The guide applies to FDA regulated clinical investigations incorporating DHTs. The term “clinical investigation” is not defined separately in the Guide; rather, the FDA refers to the term as defined in its regulations governing informed consent, IRB review, investigational new drug applications (INDs), and investigational device exemptions (IDEs). These references can be confusing because the definition of “clinical investigation” is not uniform in these related FDA regulations. While a full analysis of how these different regulations apply to research studies is beyond the scope of this Client Alert, if the study sponsor has determined that a study requires an IND or an IDE, the guide applies. The recommendations in the Guide to Informed Consent Requirements and the IRB Review are likely to apply to studies exempt from EDI as well (if the study data is to be used later in a submission to FDA) than in studies exempted from INDs of legally marketed drugs.
Recommendations for promoters, investigators and IRBs
The Guide provides recommendations to study sponsors for the use of DHT in a clinical investigation, including the following topics:
- Selection of DHTs that are suitable for use in a clinical investigation.
- Description of DHT in regulatory submissions to the FDA (which the FDA believes should include information on how the integrity of data collected by DHT will be maintained).
- Verification and validation of DHT for use in a clinical investigation.
- Definition and evaluation of clinical parameters from data collected using DHTs.
- Address DHTs in a statistical analysis plan.
- Risk Considerations When Using DHTs.
- Protection and retention of records.
Sponsors should consider each of these guidance sections when designing a clinical investigation that will incorporate DHT. The Guide also recommends that sponsors train study participants and staff on the use of DHTs, develop a technical assistance plan for study participants and staff, develop a management plan for risks to resolve potential problems study participants may encounter while using a DHT, develop a safety monitoring plan that addresses how abnormal DHT measures relate to participant safety ( eg hypoglycemia, arrhythmia, apnea) will be reviewed and managed, and ensure that data has been uploaded from DHT to a durable electronic data repository.
Note that in addition to being useful tools in clinical investigations of drugs, biologics and medical devices, some DHTs are themselves considered to be “medical devices” under the Federal Food, Drug and Cosmetic Act.1 Sponsors who plan to use DHT in a clinical investigation should be aware of the regulatory status of DHT in the context of this study. This can present pitfalls for the unwary if, for example, a “general welfare” DHT would not be a medical device as it is usually used but would be a medical device in a study because of the how DHT will be used, or whether DHT is a “significant risk device” when used in a drug or bioassay. Sponsors should engage as soon as possible with the appropriate FDA center responsible for the medical product under investigation to discuss the proposed use of DHT.
Institutions, investigators and IRB
Research sites, as well as investigators who do not sponsor a study, should ensure that participants understand what information will be collected by DHT and how the security and confidentiality of data collected by DHT will be maintained. They should also train participants in the use of DHT according to the protocol. The sponsors-investigators and the institutions sponsoring the research initiated by the researchers must, moreover, respect the requirements of the sponsors, detailed above.
Investigators, institutions that have their own IRBs, and independent IRBs should pay particular attention to section IV.F. of the guide, “Risk Considerations When Using Digital Health Technologies,” discussing potential clinical and privacy risks introduced by the use of DHTs. The FDA recommendations include, among other things, ensuring that security measures are implemented to protect data from unauthorized access, as well as notifying participants (in informed consent documents) of any consent agreements. end user license for the use of DHT which potentially grants third parties access to their collected data. In our experience, IRBs do not always assess study approval criteria in 21 CFR Part 50 and 45 CFR Part 46 individually, and do not always assess each item of informed consent required in the context of a particular study. For example, we don’t think it’s common for developers, investigators, or IRBs to consider DHT end user license agreements and terms of service when preparing and reviewing documents. informed consent (as the Department of Health and Human Services Secretary’s advisory committee on Human Research Protections said they should do so last year) when DHT is not the focus of the study , and although these stakeholders are not explicitly required to do so now, it is clear from the guide that the FDA believes they should do so in some cases. In addition to ensuring regulatory compliance, following the recommendations here for scalable technologies such as DHTs can mitigate the risk of liability and adverse public relations exposure.
We recommend that life science companies, research institutes and IRBs review the Guide now to determine what they may need to do to comply if it is released as final after the reporting period closes. commentary on March 23, 2022. Even though the guide is never finalized, as often happens with FDA guidance documents, the guide does offer important information about how the FDA thinks its existing regulations are working. apply to DHTs used in clinical investigations. Relevant stakeholders who wish to comment on the Guide can do so here.
1 For software, article 3060 of 21st The Century Cures Act introduced significant flexibility when it became law in late 2016, cutting out software functions that might previously have been regulated by the FDA as a medical device. With this flexibility comes additional complexity, however, and many FDA guidance documents have been drafted or amended over the years since the passage of the Cures Act that sponsors should be aware of when determining. if and how the FDA will regulate a particular product that is (or uses) software.