Stakeholders welcome FDA’s informed consent ‘key information’ guidance

Industry groups, clinical researchers and patient advocates praised draft guidance from the US Food and Drug Administration (FDA) and the Office of Human Research Protections (OHRP) that makes recommendations on the key information that should be included in informed consent documents used in human subjects research.

Many organizations urged FDA and OHRP to maintain the flexibility expressed in the draft guidance as they move to finalize the document.

“Consistent with the draft guidance’s support for a flexible approach to informed consent, PhRMA strongly encourages FDA and OHRP to continue to embrace flexibility and recognize that lengthy informed consent documents are generally unnecessary and, in many circumstances, can be counterproductive to the intended purpose of informed consent,” the Pharmaceutical Research and Manufacturers of America (PhRMA) wrote in comments on the draft guidance.

The draft guidance, published in March 2024, seeks to harmonize FDA’s human subject protection regulations with the revised Common Rule. Specifically, the guidance outlines how to present “key information” in a concise way at the beginning of the informed consent process. (RELATED: FDA recommends participants receive key trial information early, concisely, Regulatory Focus 4 March 2024)

The guidance discusses seven topics that are likely to be considered key information, including:

Voluntary participation and right to discontinue
Purpose of the research, expected duration and procedures
Reasonably foreseeable risks and discomforts
Reasonably expected benefits
Appropriate alternative procedures
Compensation and medical treatments for research-related injuries
Costs related to subject participation

Use of videos, illustrations

The National Organization for Rare Disorders (NORD) applauded the draft guidance for allowing the use of innovative informed consent approaches, such as videos.

“It is important to ensure that informed consent is presented in accessible manners that can be tailored to a participant's unique needs. Language barriers, hearing or vision impairment, developmental delays, as well as health literacy competencies are just some of the factors which can make it more challenging for participants to navigate the informed consent process and fully understanding the risks and benefits of participating in clinical trials,” NORD wrote.

The Pharmaceutical Research and Manufacturers of America (PhRMA), which wrote that it “strongly supports the flexible and innovative approach” taken in the draft guidance, also endorsed the idea of using illustrations and videos to convey key information. PhRMA asked the agencies to provide examples about when these non-text based methods could be used.

The Association for Clinical Oncology (ASCO) praised FDA and OHRP for providing flexible approaches to conveying information, including text boxes, bubbles, pictures and diagrams. ASCO suggested that the agencies use the appendix of the draft guidance to include additional details about what could be written for different types of trials. Specifically, they suggested an example “bubble” about insurance coverage for routine care costs, including Medicaid patients.

Flexibility on key information

On the topics of compensation and medical treatment for research-related injuries and costs related to subject participations, PhRMA suggested that the final guidance support using short statements in the key information, with in-depth information to come later in the consent form. “If this information is included in detail in the ‘key information’ section, it could overwhelm an otherwise succinct presentation; but if these details are glossed over for the sake of brevity, this discussion might have the opposite of its intended effect and end up confusing prospective subjects,” PhRMA wrote.

Moderna suggested that FDA be “flexible” on its recommendation on using prospective subject input for what is considered key information in the informed consent. That determination should be left to the clinical team and based on the study specifics, the company commented. “For example, patient advocacy groups and close partnership with families of prospective subjects may add necessary key information for rare disease studies, while this approach may differ for infectious diseases,” Moderna wrote. “The guidance should consider subject input and clinical team input in a complementary approach.”

In combined comments, the Association for the Accreditation of Human Research Protection Programs (AAHRPP) and Public Responsibility in Medicine and Research (PRIM&R) also raised concerns about routinely involving patients in the development of informed consent documents, noting that it could become burdensome for smaller organizations. They also pointed out that many organizations have already conducted this type of outreach in the past and drafted their key information templates based on that feedback.

“For example, one organization found that potential research participants wanted to know the time commitment; where they had to go to participate; what they needed to do; and what was the reimbursement or compensation for participation or if they were injured in some way. These priorities differ from what OHRP and FDA propose to include in the key information section of an informed consent document,” AAHRPP and PRIM&R wrote. “We recommend OHRP and FDA follow their own guidance and take advantage of the work organizations already have done and incorporate that knowledge into their recommendations.

Additionally, AAHRPP and PRIM&R sought more details on what reasonably constitutes “foreseeable risks” in research. The draft guidance suggests that “reasonably foreseeable risks and discomforts” should be included in the key information section of informed consent documents. But there is confusion around how much information should be included. “Confusion remains in the regulated community about what are considered reasonably foreseeable risks and discomforts, which can lead IRBs to err on the side of caution and include all potential risks in consent documents,” AAHRPP and PRIM&R wrote.

Informed consent process

AAHRPP and PRIM&R urged FDA and OHRP to address the process of informed consent overall, rather than focusing exclusively on the informed consent document itself.

“Extending the guidance to provide recommendations related to the process, especially if based on input from those skilled at obtaining informed consent, could help underscore for IRBs and others the importance evaluating the informed consent process and
not just informed consent documents,” they wrote.

The Association of American Medical Colleges (AAMC) agreed with the need to focus on the overall process of informed consent and suggested that FDA and OHRP work with the research community to expand recommendations in this area.

AAMC also noted that while the draft guidance includes recommendations for enhancing an individual’s understanding, it does not address how sponsors and Institutional Review Boards (IRBs) can measure comprehension, such as through interactive questions. AAMC recommended that FDA and OHRP include suggestions for assessing understanding of the informed consent information.

The Multi-Regional Clinical Trials Center of Brigham and Women’s Hospital and Harvard (MRCT Center) suggested that FDA and OHRP could strengthen the guidance by addressing the importance of testing key information for accessibility, including font choice and size, color contrast, text spacing, line height, saturation and screen readability. MRCT Center also noted that the guidance should include a mention that it is critical to maintain plain language and accessibility in translated documents.

Patient reimbursement

The Advanced Medical Technology Association (AdvaMed) used its comments to urge FDA, and the US Department of Health and Human Services (HHS) more broadly, to change its human subject protection guidance to create safe harbors for financial assistance so that transfers of high value, such as childcare reimbursement or transportation vouchers, would not be considered violations of the federal Anti-Kickback Statute (AKS).

“The [Office of the Inspector General] recently released an Advisory Opinion (No. 23-11) indicating that subsidization of certain Medicare cost-sharing obligations for study participants in a clinical trial would not implicate civil money penalties under the AKS of the Social Security Act, or the civil money penalties under the prohibiting inducements to beneficiaries’ provision, or the exclusion authority also under the Social Security Act. While this Advisory Opinion is helpful, a broader safe harbor that applies to multiple medical device types, trial designs and common reimbursement scenarios is needed,” AdvaMed wrote.

Public comments

Stakeholders welcome FDA’s informed consent ‘key information’ guidance

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