Last week, the U.S. Food and Drug Administration (FDA) issued draft guidance on Good Clinical Practice (GCP), adopting the International Council for Harmonisation’s (ICH) “E6(R3)” guidelines. Below we summarize how the draft guidance would modernize GCP trial standards and promote the use – as well as the agency oversight – of digital health technology (DHT) and decentralized clinical trial (DCT) elements while maintaining fundamental data integrity and human subject protection considerations central to clinical research.
FDA seeks comments on the draft guidance through September 5, and is separately hosting a webinar on its decentralized clinical trial draft guidance today.
Good Clinical Practice (GCP) is the international, ethical, scientific, and quality standard for the conduct of trials that involve human participants. Last week, FDA published the 81-page draft guidance “E6(R3) Good Clinical Practice (GCP)” (Draft E6 GCP Guidance) which aims to update and supplement the 69-page March 2018 guidance “E6(R2) Good Clinical Practice: Integrated Addendum to ICH E6(R1).” The new draft guidance is adopted from ICH’s May 2023 E6(R3) draft guideline, and it expands upon FDA’s April 2022 final guidance, “E8(R1) General Considerations for Clinical Studies,” which is based on ICH guidelines of the same name.
FDA’s new draft guideline expands on the roles and responsibilities of institutional review boards (IRBs), investigators, and sponsors in the context of rapidly developing technological and methodological innovations in the clinical trial enterprise.
Digital Health Technology oversight
The most significant enhancements FDA proposes in the Draft E6 GCP Guidance are those clarifying the use of computerized systems in clinical trials, the roles and responsibilities of trial sponsors and investigators with respect to data governance, and requirements for obtaining and documenting electronic informed consent (in paper or electronic format).
FDA’s Draft E6 GCP Guidance encourages the use of digital health technologies (DHTs) that could assist with data collection or patient recruitment, such as wearable sensors. It says clinical trial design should use “risk-based proportionate approaches” that determine which protocols are most important for the protection of patient safety and data, and the guidance urges investigators to take an early focus on ensuring the clinical trial data quality.
The Draft E6 GCP Guidance includes a section named “Data Governance – Investigator and Sponsor,” which offers recommendations on procedures and processes for the use, security, and validation of computerized systems. This section also provides guidance about how to develop processes to ensure data integrity, traceability, and security throughout the full data life cycle. Rather than placing data governance responsibilities squarely at the feet of the sponsor or the investigator, the Draft E6 GCP Guidance references the “responsible party,” which could be either the sponsor or the investigator, or both; FDA is signaling here that both parties may share responsibility for data integrity.
FDA’s focus on DHT oversight in the Draft E6 GCP Guidance can be viewed as a continuation of the agency’s initiatives in this space. For instance in March, FDA issued separate draft guidance on electronic records that similarly prioritized DHT oversight, which we analyzed online here. Indeed, in a statement announcing the new electronic records guidance, FDA Commissioner Robert M. Califf, M.D., said “modernized GCP recommendations encourage the use of fit-for-purpose innovative…DHTs, such as wearable sensors [that] could potentially facilitate more agile data collection and assist with patient recruitment.”
The greater emphasis on processes & procedures to promote data integrity in the Draft E6 GCP Guidance is worth viewing in light of FDA’s expanded authority to inspect a wider range of parties involved in clinical research, such as contractors who provide biostatistical support or database services, which we recently analyzed online here. Accordingly, clinical trial sponsors, CROs, vendors, and clinical trial sites must take extra care in ensuring compliance with FDA GCP expectations.
Decentralized Clinical Trial use
FDA’s Draft E6 GCP Guidance includes many references to decentralized clinical trials (DCTs). In a traditional clinical trial, a study subject would engage in study activities at a single, centralized site (often research medical centers) that was under the immediate supervision of a site-based health care professional. By contrast, DCT trials are those where some or all trial activities take place at a location other than a traditional site. Examples of how a clinical trial may be decentralized include obtaining laboratory tests at a local facility rather than a research medical center, or conducting a clinical follow-up visit in the study subject’s home using telemedicine (including DHTs).
The Draft E6 GCP Guidance notes that consent for participation in a trial can be obtained remotely and that auditing of a trial process can as well. According to the guidelines, clinical trial design should include a discussion of whether decentralized elements will be involved. Monitoring during a study “may include site monitoring (performed on-site or remotely) and centralised monitoring, depending on the monitoring strategy and the design of the clinical trial” and it “may include secure, remote, direct read-only access to source records, other data acquisition tools and essential record retention systems,” the draft guidance states.
FDA recently issued other documents that complement these draft recommendations and promote innovative trial designs; for example, last month the agency released draft guidance proposing recommendations for the implementation of DCTs, which we analyzed online here. We see the agency’s move toward promotion of DCTs as a historic sea change that will lead to major changes in how clinical research is conducted in the U.S., with the emerging DCT framework embracing a distributed model where study-related activities can take place at the clinical site, a patient’s home, the office of another health care professional, or even a local pharmacy.
FDA seeks comments on the Draft E6 GCP Guidance through September 5, 2023. If you may wish to submit a comment or have any questions on Good Clinical Practice standards more generally, feel free to contact any of the authors of this alert or the Hogan Lovells attorney with whom you generally work.
