Guidance Document Summary: Unpacking FDA’s Guidance Document on Informed Consent

The FDA issued guidance in August 2023 to provide more clarity to IRBs, clinical investigators, and sponsors in complying with FDA’s informed consent regulations for clinical investigations. The document also includes a series of frequently asked questions.

“This new guidance is a convenient compilation of regulations and related considerations pertaining to the informed consent process,” said Edith Paal, MSJourn, MPH, CIP, CHRC, who is the Director of the University of Arkansas for Medical Sciences (UAMS) IRB.

“In our case,” Paal told PRIM&R, “it specifically addresses several issues on which we are continuously providing education, such as the difference between undue influence and coercion, and that the informed consent process begins at recruitment. Having this comprehensive reference available will help us provide needed information to study teams and IRB staff and reviewers.”

Paal noted that the length of this guidance and its citing of numerous other resources “highlight the complexity of informed consent processes in general.”

“Sponsors, IRBs, and investigators must ensure that informed consent processes and materials allow for a meaningful exchange of information, and that they don’t just check the regulatory boxes,” Paal said.

As the guidance document makes clear, in medical studies regulated by the FDA, subjects must agree to participate, through informed consent. However, there are exceptions for critical situations such as emergencies, military actions, or public health crises. The document also notes, in the “Exceptions to Informed Consent” section, that “FDA issued a proposed rule that, if finalized, would allow IRBs responsible for the review, approval, and continuing review of clinical investigations to approve an informed consent procedure that waives or alters certain informed consent elements or that waives the requirement to obtain informed consent for certain minimal risk clinical investigations.”

That said, a central point in the “Coercion and Undue Influence” section is that “the consent process and form should emphasize that an individual’s participation is truly voluntary.”

The guidance cites the Belmont Report in that, “Coercion occurs when an overt threat of harm is intentionally presented by one person to another in order to obtain compliance. Undue influence, by contrast, occurs through an offer of an excessive, unwarranted, inappropriate or improper reward or other overture in order to obtain compliance.”

Coercion and undue influence can happen in various situations, not just with specific groups. For instance, in a study that collects extra tissue samples during surgery, waiting until the patient is about to have the operation could make them feel pressured, the guidance document states.

The guidance document also makes clear that all information being given to a prospective subject, whether orally or in written documents, be presented in clear, understandable language.

The consent process must not include language that makes subjects give up their legal rights or suggests that the investigator, sponsor, institution, or its agents are not responsible for negligence. Such language is termed “exculpatory” and includes statements that would waive compensation rights or absolve the institution from financial responsibility for injury treatment.

Instead, language could be included that states, the following: “You do not give up any of your legal rights by being in this study, and you may choose to pursue legal action if you are injured by being in the study.” In short, the aim is to ensure that subjects’ rights are protected, and they are not discouraged from seeking legal recourse if needed.

PRIM&R reached out to a range of thought leaders and IRB practitioners to help distill the updates. Jessica Macha, Director, IRB, Office of Research and Education, at Corewell Health, said “The Guidance for IRBs, Clinical Investigators, and Sponsors” provides comprehensive guidance offering insights into how the FDA approaches the topic.

“While the content in this section will be familiar to most, I found it to be worth the read,” Macha said. “For example, the FDA provided sample language on how to approach injury disclosure, how to state benefits and what the FDA considers (and doesn’t consider) to be unduly influential during the consent process.”

Macha continued, “It is helpful information for IRBs that often struggle with these topics. The guidance also codifies the guidance published by the FDA during the COVID-19 pandemic that offered alternative ways to document and store consents from patients in isolation.”

“I am glad to see that the FDA found some of the proposed alternative documentation methods useful and could be applied in other situations outside of a national public health emergency,” Macha said. “Lastly, the FDA added new answers to common questions related to consent of special and vulnerable populations that can provide additional value to the IRB’s review process.”

Erica J. Heath, CIP, Retired Founder and President, IRC, recognized the timing of the publication of this document.

“Finally! This final document on informed consent is issued on the 25th anniversary of FDA’s only full guidance document on informed consent,” Heath said. “It was issued as a draft in 2014, before the Common Rule update. This new final document is a welcome addition to FDA’s set of guidance documents, as it compiles several other documents and serves to bring together FDA’s current thinking on the process and documentation of and responsibilities for informed consent. It contains no surprises.”

“FDA is in a bit of a quandary,” Heath said. “FDA has not harmonized with the Common Rule although it is in the middle of the notice and comment rulemaking process. It promises to be a long road and it seems that they decided to issue this guidance as an interim measure. As a result, this is a relatively simple, direct and unadorned summary of FDA’s informed consent regulations all in one place.”

Ada Sue Selwitz, MS, the Executive Integrity/Compliance Advisor at the University of Kentucky, summed up the document as a framework “to ensure compliance with FDA regulatory expectations pertaining to informed consent process and documentation.”

This guidance, according to the FDA, supersedes the guidance titled “A Guide to Informed Consent,” issued in September 1998, and finalizes FDA’s draft guidance titled “Informed Consent Information Sheet,” issued in July 2014.

Read the full document.

This article was originally published in the September 2023 PRIM&R Member Newsletter. Click here to become a PRIM&R member and join our supportive membership community that provides resources and connections with colleagues from more than 1,000 institutions in more than 40 countries.