On March 1, 2024, the U.S. Food and Drug Administration (FDA) and the U.S. Department of Health and Human Services’ (HHS’s) Office for Human Research Protections (OHRP) released a draft guidance titled “Key Information and Facilitating Understanding in Informed Consent[:] Guidance for Sponsors, Investigators, and Institutional Review Boards” (“draft guidance”).

On its website, FDA reminded research stakeholders that “[i]t is the research community’s ethical obligation to ensure that . . . individuals understand the purpose and the potential risks and benefits of the research before agreeing to participate.” FDA noted, however, that too often, “informed consent forms are lengthy and difficult for potential research participants to understand.”

To improve this process, the draft guidance addressed how best to present key information in research consent forms and includes FDA’s and OHRP’s recommendations for the content, organization, and presentation of informed consent information in FDA-regulated clinical investigations of medical products and in HHS-supported or -conducted nonexempt human subjects research. Although not binding on research stakeholders, the draft guidance, once finalized, is intended to assist institutional review boards (IRBs), investigators, and sponsors engaged in or responsible for oversight of human subject research subject to FDA and/or HHS regulations with the development of compliant consent information. 

The draft guidance also represents another step in the overall plan to harmonize HHS’s revised Federal Policy for the Protection of Human Subjects (“Common Rule”) with the relevant FDA regulations. This harmonization—mandated by section 3023 of the 21st Century Cures Act, Pub. L. No. 114-255 (Dec.13, 2016)—is aimed at (i) reducing the regulatory burdens on IRBs, sponsors, and investigators and (ii) simplifying and facilitating compliance while simultaneously protecting the rights, safety, and welfare of human subjects. As a reminder, in September 2022, FDA issued two Notices of Proposed Rulemaking: (i) the “Protection of Human Subjects and Institutional Review Boards NPRM” (HS NPRM) aimed at harmonizing FDA’s regulations pertaining to human subjects research with those of the revised Common Rule, and (ii) “Institutional Review Boards; Cooperative Research” aimed at harmonizing FDA’s regulations pertaining to the review of cooperative research by a single IRB with those of the revised Common Rule. 

Comments on the draft guidance are invited through April 30, 2024, and should be made as described in the Federal Register notice, citing Docket Number FDA-2022-D-2997.

Provision of Key Information

The revised Common Rule requires consent information to “begin with a concise and focused presentation of the key information that is most likely to assist a prospective subject or legally authorized representative in understanding the reasons why one might or might not want to participate in the research” (45 CFR 46.116(a)(5)(i)). FDA’s proposed regulations in the HS NPRM would add identical language to 21 CFR 50.20(e)(1). As summarized below, the draft guidance not only included several recommendations regarding how best to draft the key information section of a consent form to help facilitate discussions between a prospective research subject and an investigator about the research but also reminded stakeholders that the section should be “relatively short,” meaning limited to “generally no more than a few pages.” Helpfully, FDA and OHRP also provided a sample key information section for a hypothetical clinical trial in the draft guidance’s appendix.

Flexible Approaches

FDA and OHRP recognized that there are multiple strategies for providing key information to prospective research subjects in a way that would be consistent with the provisions of the revised Common Rule and FDA’s proposed regulations in the HS NPRM. The agencies encouraged the exploration and development of innovative ways to provide key information that will help prospective subjects better understand the reasons why one might or might not want to participate in the research, including utilization of available technologies and alternative media (e.g., illustrations, video, and electric tablets).

Addressing Basic and Additional Elements of Informed Consent in the Key Information Section

FDA and OHRP were clear in their recommendation that the key information section need not include each element of informed consent contained in 45 CFR 46.116(b) and (c) or in 21 CFR 50.25(a) and (b), including the proposed revisions to that section, clarifying that which of the basic and additional consent elements should be included will vary based on factors such as (i) the study attributes and its design; (ii) the condition(s), behavior(s), or outcome(s) being examined; and (iii) the prospective subject population. Elements not addressed in the key information section would still need to be included elsewhere in the document, as required. If appropriate, the draft guidance notes that the elements of informed consent that are addressed in the key information section can also be repeated more comprehensively in other parts of the consent form to further help clarify concepts and ensure that the entire consent form remains understandable to prospective subjects. In the draft guidance, FDA and OHRP identified the following list of topics that are likely to be considered key information:

1. Voluntary Participation and Right to Discontinue Participation
2. Purpose of the Research, Expected Duration, and Procedures to Be Followed
3. Reasonably Foreseeable Risks and Discomforts
4. Reasonably Expected Benefits
5. Appropriate Alternative Procedures
6. Compensation and Medical Treatments for Research-Related Injuries
7. Costs Related to Subject Participation

Supplemental Information

The draft guidance notes that while not required, supplemental information beyond the basic and additional consent elements may be included in the key information section when it is likely to be important to the prospective subject’s decision about research participation (e.g., the risks to others not participating in the study, but who nevertheless could be impacted by the potential subject’s participation in it). FDA and OHRP pointed to the HHS Secretary’s Advisory Committee on Human Research Protections’ (SACHRP’s) recommendations[1] on this issue and the questions that can be used to help identify which supplemental information would be appropriate to include with the key information for a particular study.

Facilitating Understanding

The revised Common Rule at 45 CFR 46.116(a)(5)(ii) requires that “informed consent as a whole must present information in sufficient detail relating to the research and be organized and presented in a way that does not merely provide lists of isolated facts, but rather facilitates the prospective subject’s or legally authorized representative’s understanding of the reasons why one might or might not want to participate.” FDA’s proposed revisions to its regulations at 21 CFR 50.20(e)(2) would also include this requirement. FDA and OHRP included several recommendations on how consent forms can be organized and presented in a way to facilitate potential subjects’ understanding of the research, including:

1. organizing (i) the key information within a simple, concise format within a defined border, such as a bubble (i.e., rounded boxes creating a discrete unit of information), and (ii) the rest of the consent information in other appropriate information organization methods (e.g., formatting text into two columns, using bullet points, etc.);
2. following plain language principles for the entire consent form (e.g., a combination of text-based and visual approaches);
3. presenting information in sufficient detail throughout the consent form;
4. thoughtfully organizing and presenting the consent form contents (e.g., using a tiered approach to presenting the information for more complex studies); and
5. using language at a level prospective subjects would likely understand (e.g., including explanations for scientific and medical terms).

By issuing this draft guidance, FDA and OHRP are building upon the revised/soon-to-be-revised regulations to improve the informed consent process for research subjects and advance the application of the ethical principle of respect for persons. Overall, the draft guidance provides helpful recommendations that interested parties should consider when drafting a consent form for FDA-regulated clinical investigations of medical products and for HHS-supported or -conducted nonexempt human subjects research to facilitate compliance with the applicable regulations. 

ENDNOTE

[1] See SACHRP’s October 17, 2018, Recommendations – Attachment C: New “Key Information” Informed Consent Requirements.

Ann Parks contributed to this article.