Our Comments on FDA Guidance Regarding Decentralized Clinical Trials for Drugs, Biological Products, and Devices

August 1, 2023

We are pleased to have the opportunity to share our views with the Food and Drug Administration (FDA) on their draft guidance regarding Decentralized Clinical Trials (DCTs) for Drugs, Biological Products, and Devices.

We are a nonprofit think tank that conducts, analyzes, and scrutinizes research on a range of health issues, with a particular focus on which prevention strategies and treatments are most effective for which patients and consumers. We do not accept funding from companies that make products that are the subject of our work, so we have no conflicts of interest.

DCTs have the potential to increase inclusion of underserved or rural communities and patients who are home-bound. It reduces geographic barriers by enabling patients to participate in clinical trials even if they do not live near a study site. This is much more convenient than traveling to a conventional study for medical interventions, data collection, assessments, and follow-up visits. However, the FDA and those conducting DCTs must also recognize how they could inadvertently reduce the enrollment of diverse populations when relying on digital health technologies (DHTs). The inability to access DHTs or lack of familiarity or comfort with DHTs could limit or prevent enrollment of older adults and children, participants living in rural areas, people who speak a language other than English, and people who have lower literacy skills or lower income. We recommend that FDA revise the guidance to incorporate the following strategies when implementing DCTs, including those that use DHTs:

  1. The guidance should incorporate information on how patients who decide to use their own DHTs during DCTs differ from those individuals who are provided a DHT during the study. Patients who regularly use these tools before study participation may differ in terms of several baseline health characteristics, vary in socioeconomic status, or have different health habits than those who do not have DHTs. Data recorded during a trial should include information on a participant’s prior device experience, as well as reasons for use, and include these variables in study analysis, as prior experience with a device could affect outcomes.
  2. DCTs using DHTs should consider and plan for the consistent availability and use of the same DHTs over time, even if newer versions of a device are introduced, as these updates could affect trial performance. Additionally, DHTs that require software on a participant’s phone or computer could undergo multiple app updates over the course of the study, with the potential to add new features that affect data input. Investigators must plan to follow-up with participants whenever major software updates occur.
  3. The FDA guidance mentions that sponsors should consider syncing information recorded by DHTs across different platforms. Digital health sources such as electronic health record (EHR) portals or portals linking data from personal digital devices, can be disconnected during the course of the DCT and require significant additional effort to reconnect. These disconnections can come from password changes and security issues which can result in the loss of data, which may be temporary or permanent depending on the willingness or ability of the participant to reconnect. Planning for this possibility is essential to ensure comprehensive data capture. Study teams should regularly review the completeness and quality of the DHT data over the course of the study to reduce missing data.
  4. The guidance mentions that, “training should be provided to all parties (e.g., trial personnel, local HCPs, and trial participants)” related to the software used in DCTs. This should apply to all DHTs and, as appropriate, should include caregivers who may assist study participants during DCTs.
  5. Although FDA states that researchers “should attempt” to collect data regarding healthcare services provided outside the study site. This does not adequately provide explicit directions on how to provide information regarding unexpected or routine visits to non-study sites, such as an ER visit for an adverse event that may or may not be obviously related to the clinical trial. The FDA guidance recommended that providers outside of the clinical trial not be included in the task log, which tracks health care providers that perform trial-related activities. However, if that information is not collected and evaluated, then significant information about safety issues would inevitably be missed. FDA should explicitly address how potentially important information should be included in the task log and re-evaluate the need to include these data points.