The draft guidance provides recommendations on how to present key information at the start of an informed consent process, which should include topics that are generally important for clinical trial participants to understand, including: the purpose of the research, the possible risks and benefits of the study, and the study’s length and procedures. The recommendations apply to FDA-regulated clinical investigations of drugs, devices, and biologics, as well as to HHS-supported or -conducted nonexempt human subjects research. Notably, the recommendations also apply to consent documents developed for emergency research studies, under 21 CFR 50.24, that are not subject to the general informed consent requirements, and to expanded access studies.

According to HHS, the recommendations in the draft guidance align with the Federal Policy for the Protection of Human Subjects, known as the “Common Rule,” revisions to which came into effect in 2018. Specifically, the guidance provides research sponsors, investigators, and IRBs with recommendations on how to implement two requirements in FDA’s September 2022 proposed rules on harmonizing human subject research regulations with the revised Common Rule, including that informed consent:

• begin with key information about the research presented in a clear and concise manner; and,

• is presented in a way that facilitates understanding of the reasons why someone might or might not want to participate in the research.

FDA’s 2022 proposed rules have yet to be finalized, and are titled “Protection of Human Subjects and Institutional Review Boards” and “Institutional Review Boards; Cooperative Research.” Our analysis of those proposals is online here.

To help implement the requirements of the proposed rules, the draft guidance explains how to present elements of informed consent in a “concise and focused” key information section, including:

1. Voluntary participation and the right to discontinue participation

2. The trial’s purpose, expected duration and procedures

3. Reasonably foreseeable risks and discomforts

4. Reasonably expected benefits

5. Appropriate alternative procedures

6. Compensation and medical treatments for trial-related injuries

7. Participation-related costs

In addition to recommendations on the content of an informed consent document, the draft guidance makes several recommendations for how that content reaches prospective participants. The Agency encourages sponsors to develop innovative ways to communicate the information, including by consulting with patient advocacy groups or prospective participants to better understand which information is most important to participants and tailor methods to foster understanding. The draft guidance also proposes various flexible and innovative strategies to facilitate understanding among prospective participants, which derive from the agency’s research on consumer understanding from drug labels. These strategies include using alternative media (e.g., illustrations or videos); using rounded boxes or bubbles to create discrete units of information; formatting texts into two columns; using plain language incorporating texts and pictures or diagrams; and using hyperlinks and cross-references to related topics. The guidance illustrates these approaches in an appendix, providing concrete instruction on how to implement these strategies.

In an FDA “Voices” blog post accompanying the draft guidance release, CDER Director Patrizia Cavazzoni, M.D., and CDER Chief Medical Officer Hilary Marston, M.D., M.P.H., emphasized the research community’s ethical obligation to ensure that patients understand the purpose and the potential risks and benefits of research before agreeing to participate, opining that “[t]oo often…informed consent forms are lengthy and difficult for potential research participants to understand.”

This new draft guidance comes on the heels of FDA’s lengthier, long-awaited final guidance on informed consent, which we analyzed online here, and which provided essential clarifications on the broader informed consent process and elements, as well as alternative methods of obtaining consent. Similar to this draft guidance, that final guidance advocates for obtaining informed consent in language that is “understandable” and at a reading level that the participants can comprehend.

This latest guidance also builds on the agency’s December 2023 final rule on IRB informed consent waivers for minimal risk clinical trials, which we summarized online here, and which similarly aimed to conform FDA’s regulations with the revised Common Rule. OHRP also has released several education and outreach materials in recent year, focused on distinct aspects of the Common Rule (45 CFR Part 46). Viewed together, the agency’s latest efforts are part of a broader effort by federal agencies to harmonize regulations governing human subjects research and demonstrate an increasing regulatory focus on protecting patients in clinical research and safeguarding their right to give informed consent.

HHS seeks comments on the draft guidance through April 30, 2024. If you wish to submit a comment, or have any questions on informed consent issues or clinical research more generally, feel free to contact any of the authors of this advisory or the Hogan Lovells attorney with whom you regularly work.