PRIM&R’s Response to the FDA’s Draft Guidance on Informed Consent

by Avery Avrakotos, Education and Policy Manager

PRIM&R has long been committed to the protection of the rights and welfare of human subjects, and strongly believes that informed consent is an essential mechanism for providing potential subjects with the information they need to make considered, autonomous decisions about research participation.

In July, the US Food and Drug Administration (FDA) announced it was seeking comment on a draft guidance document titled “Informed Consent Information Sheet: Guidance for IRBs, Clinical Investigators, and Sponsors.” The draft is a substantial revision to the FDA’s prior guidance on this topic, which was issued by the agency in September 1998. Yesterday, PRIM&R’s Public Policy Committee, which is composed of experts from a wide range of disciplines and institutional settings, responded to the agency’s request with a set of comments on the draft guidance.

In its response, PRIM&R commends the FDA for encouraging investigators to think of informed consent as not simply a form, but rather a dynamic process that can be adapted to reflect the unique needs of potential subjects, as well as local context. PRIM&R also thanks the FDA for its efforts to harmonize regulatory requirements and guidance for human subjects research put forward by the Department of Health and Human Services, the Office for Human Research Protections, and the FDA. PRIM&R’s comments also applaud the addition of expanded sections on informed consent with respect to vulnerable populations and the agency’s consideration of the use of new technologies for obtaining informed consent.

PRIM&R comments also identify several areas where further guidance could benefit IRBs, investigators, sponsors, and, ultimately, subjects:

The Consent Form Versus the Consent Process
In a recent blog post, PRIM&R’s executive director, Elisa A. Hurley, PhD, discussed how the language we use to talk about informed consent can have an effect on our general attitudes toward consent. Along those same lines, in its comments, PRIM&R urges the FDA to replace the term “consent interview” with the term “consent discussion,” which more accurately reflects the desired tenor—an exchange of information between two parties—of such interactions. PRIM&R also recommends that the FDA carefully consider how it explains the purpose of the consent form, as what is said in the guidance document is likely to have far-reaching effects on the content of consent forms. As a final point, PRIM&R asks the agency to provide greater clarity regarding the form and function of the consent discussion, as well as its relationship to the consent form.

Presentation of Risks
In the draft guidance, the FDA acknowledges that reducing length may increase the readability of consent forms. PRIM&R commends the agency for this recognition, but cautions that the call for disclosure of any reasonably foreseeable risks associated with the medically recognized standard care and appropriate alternatives seems likely to perpetuate the problem of overly long and complicated forms. PRIM&R believes the consent form, as well as the consent discussion, should focus on presenting potential subjects with the information that is most likely to be significant to their decisions to participate in research. In its comments, PRIM&R also recommends a framework— making a distinction between “risks” and “side effects” associated with a clinical investigation—that investigators, IRBs, and sponsors can utilize when determining which risks should be considered “reasonably foreseeable,” and thus, most likely, germane to a potential subject’s decision to participate.

Responsibilities of Investigators
One of the strengths of the draft guidance is the addition of clear information on the respective responsibilities of IRBs, investigators, and sponsors for informed consent, as all of these parties have an essential role to play in the informed consent process. In its comments, PRIM&R offers several additional recommendations with respect to the responsibilities of investigators. PRIM&R asks the FDA to consider requiring investigators and/or research staff to attest that they have discussed the risks, benefits, and alternatives and provided the potential subject with an opportunity to ask questions, and that, in their judgment, the potential subject understands the information that has been presented and has voluntarily chosen to participate in the clinical investigation. PRIM&R also asks the FDA to encourage investigators to consider the order in which information is presented in the consent discussion and to utilize alternative approaches to information disclosure that will enhance the discussion, such as videos or online resources.

Understandable Language
From the outset, the FDA recognizes in the draft guidance that the health literacy and numeracy (quantitative literacy) of many US adults are at a basic level. In its response, PRIM&R commends the FDA for recognition of this fact, and makes several additional recommendations intended to ensure that language used throughout the consent process is understandable to potential subjects. As a starting point, PRIM&R asks the FDA to recommend that scientific and medical terms only be used when necessary and, whenever possible, as parentheticals to ordinary language descriptors. Given the limited quantitative literacy of many US adults, PRIM&R also asks the FDA to provide clearer guidance on the presentation of quantitative information to potential subjects, for instance, the most effective way to present the likelihood of potential risks and benefits. As a final point, PRIM&R asks the FDA to ensure that all sample language provided in the draft guidance is consonant with its recommendations regarding the use of understandable language.

Enrollment of Non-English-Speaking Subjects
The principle of justice requires that no specific population either be unfairly excluded from the potential benefits of research or unduly subjected to its burdens. When barriers to enrolling individuals from a specific population, such as non-English speakers, are high, concerns related to the principle of justice arise. In its comments to the FDA, PRIM&R raises concerns about certain requirements for the unexpected enrollment of non-English-speaking subjects—including the post-hoc provision of a translated long form to subjects who have already participated in a consent discussion and enrolled in the research—which PRIM&R believes may carry significant financial and administrative burdens, without evidence that such requirements will enhance subject protections. PRIM&R asks the FDA to reconsider these requirements with the principle of justice in mind.

I encourage you to take a moment to read PRIM&R’s complete response to the FDA, and to share your thoughts about PRIM&R’s comments or the FDA’s draft guidance below.