The U.S. Food and Drug Administration (FDA), in collaboration other agencies, recently published draft guidance (Guidance) on effectively presenting key information regarding informed consent in FDA-regulated clinical investigations of medical products and Department of Health and Human Services (HHS) supported human subjects research. The Guidance aims to assist sponsors, investigators, and institutional review boards (stakeholders) involved in or tasked with overseeing human subject research. In particular, the Guidance provides an overview on how to effectively present key information, offering recommendations for the content, structure, and delivery of informed consent.

Background

FDA regulations in 21 C.F.R. parts 50 and 56 are designed to protect human subjects participating in FDA-regulated clinical investigations, ensuring their rights, safety, and welfare. Following revisions announced by HHS on January 19, 2017 (Revised Common Rule), efforts have been made to enhance protection for human subjects and streamline research processes. Section 3023 of the Cures Act mandates the alignment of differences between HHS and FDA regulations, prompting a proposed rule to amend the aforementioned 21 C.F.R. sections for “harmonization.” FDA further plans to incorporate parts of the Revised Common Rule into 21 C.F.R. § 50.20(e) in support of its ongoing efforts to ensure consistency in regulations governing human subject protection.

Informed Consent Criteria

The Revised Common Rule dictates that consent information is to:

Begin with a concise and focused presentation of the key information that is most likely to assist a prospective study subject or legally authorized representative in understanding the reasons why one might or might not want to participate in the research. See 45 C.F.R. § 46.116(a)(5)(i)).

The FDA, therefore, recommends that stakeholders carefully identify key information when obtaining informed consent to ensure a participant’s understanding of the research risks, benefits, and procedures, thereby promoting their ability to make informed decisions about participation.

Identification of Key Information

The FDA recommends starting the key information section of the consent form with an introductory statement to guide prospective study subjects. It is unnecessary for this section to include every element of informed consent; instead, stakeholders should prioritize including the most essential elements for a particular study, considering what would be important information to study participants. To aid stakeholders, FDA proposes the following content to include as part of the presentation of key information.

Voluntary Participation and Right to Discontinue Participation

The FDA recommends stating in the key information section that participation in the research is voluntary, with no penalties or loss of benefits for declining or withdrawing from participation in the study. Additionally, stakeholders should reassure prospective study subjects that their decision regarding study participation will not affect their relationship with health care providers or their medical care.

Purpose of the Research, Expected Duration, and Procedures to be Followed

The key information section of the consent form should effectively communicate essential details to prospective study subjects, facilitating their understanding of the study’s purpose and protocol, such as its design and inclusion criteria. Key details may include the expected duration of participation, procedures involved, the status of investigational products, and any experimental procedures. Additionally, stakeholders should consider including information on placebo use, randomization, post-study options, and how participation compares to standard care.

Reasonably Foreseeable Risks and Discomforts

The FDA recommends providing information upfront about the most common and serious risks associated with participation in the study to assist prospective study subjects when making informed decisions about participation. Key risks should be prioritized and clearly distinguished from other research interventions and may encompass details on risk monitoring and mitigation strategies to ensure prospective study subjects are thoroughly informed.

Reasonably Expected Benefits

The key information section should emphasize any potential benefits of research participation, as these may influence prospective study subjects’ decisions. However, it is important to ensure that prospective study subjects understand the distinction between research and clinical care, and any potential benefits should be presented in a clear and realistic manner without conveying overly optimistic expectations.

Appropriate Alternative Procedures

Incorporating a clear and concise description of alternative procedures or treatments, if applicable, is essential in the key information section to inform prospective study subjects’ decision-making regarding participation in the study. It is recommended to provide information about the care prospective study participants would receive outside the study first, followed by details on how the care provided in the context of the study differs, emphasizing awareness of alternatives tailored to individual values and preferences.

Compensation and Medical Treatments for Research-Related Injuries

For research involving more than minimal risk, it is recommended to include details about available medical treatments and compensation for prospective study subjects in case of injury as key information, particularly if there are no plans for compensating for treatment costs related to research-related injuries.

Costs Related to Subject Participation

Interested parties should consider including information about potential costs incurred by prospective study subjects, including whether health insurance may be charged and if reimbursement for study-related expenses will be provided. Additionally, incentives and payments for time, inconvenience, and discomfort should also be addressed as key information, as these issues can impact prospective study subjects’ decisions to participate.

Supplemental Information

Supplemental information beyond basic consent elements can be added to the key information section if it’s important to the prospective study subject’s decision about research participation. HHS Secretary’s Advisory Committee on Human Research Protections suggests considering various aspects, such as the novelty of the research and impacts on subjects outside of the study, to identify relevant information to include.

Presentation of Key Information

The Revised Common Rule also 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 study subject’s or legally authorized representative’s understanding of the reasons why one might or might not want to participate. 45 C.F.R. § 46.116(a)(5)(ii)

Stakeholders are advised to prioritize presenting key information concisely at the outset of the informed consent process. The FDA emphasizes the need for clear and well-organized consent forms across various presentation formats, including written, oral, or electronic mediums. To enhance comprehension, stakeholders are encouraged to explore innovative methods like utilizing illustrations or tablet devices. Additionally, consent documents should adhere to plain language principles, prioritize essential information, and adopting a tiered structure, presenting key details first and additional information as needed. Customizing information to match the audience’s language proficiency, education, and cognitive abilities is critical for facilitating understanding and informed decision-making regarding participation in a study.

Conclusion

The FDA’s Guidance offers recommendations for effectively presenting key information in FDA-regulated clinical investigations and HHS-supported human subject research. The Guidance aligns with efforts to enhance protection for human subjects and streamline research processes. By prioritizing concise presentation and innovative methods, stakeholders can promote informed decision-making among prospective study participants, ensuring consistency and clarity in regulations governing human subject protection. Foley & Lardner will continue to monitor the development of this proposed rule to provide timely updates and insights to our readers.