Background

On October 30, 2024, FDA held a Patient Engagement Advisory Committee (PEAC) meeting to focus on "Patient-Centered Informed Consent in Clinical Study of FDA-Regulated Medical Products." At the meeting, speakers discussed ways to improve the informed consent process in clinical trials by enhancing trial participant engagement and understanding. The meeting began with several presentations by agency officials, aimed at emphasizing patient-centric informed consent processes and providing updates on FDA guidance, initiatives, and expectations.

In his opening address, FDA Commissioner Robert M. Califf, M.D., encouraged sponsors to move beyond viewing informed consent as merely a “paper trail.” He emphasized “shared decision-making” and the need for patient involvement in shaping research policies. Michelle Tarver, M.D., PhD., Director of FDA’s Center for Devices and Radiological Health (CDRH), highlighted several key initiatives, including the upcoming November 20 discussion by the FDA Digital Health Committee on AI-enabled devices. She also discussed "Home as a Healthcare Hub," an innovative project focused on viewing “the home environment as an integral part of the health care system” by collaborating with patient groups, health care providers, and the medical device and consumer technology industry to build virtual reality home prototypes. Additionally, Tarver spoke about a recent CDRH paper on Health Equity, underscoring the need for more inclusive healthcare solutions. These initiatives, and the recent CDRH paper, reflect FDA’s commitment to advancing informed consent through more inclusive, accessible, and patient-centered healthcare solutions, reinforcing the idea that consent is an ongoing, participatory process rather than a one-time agreement.

Representatives from FDA’s Office of Clinical Policy also provided a comprehensive overview of informed consent, emphasizing that it is a continuous dialogue, rather than merely a one-time event. They also discussed FDA’s March 2024 Guidance on Informed Consent, and underscored the potential benefits of e-consent for improving accessibility and patient engagement.

Topics of discussion

Several critical topics were discussed regarding the informed consent process in clinical trials, focusing on bridging the gap between existing research, best practices, and real-world implementation. Despite significant developments in guidance and research over the past few years, presenters expressed concern that real-world consent processes still fall short of reflecting these best practices, particularly in ensuring patient understanding. As discussed during the meeting, and outlined in FDA’s Executive Summary following the meeting, shortcomings in patient understanding can be attributed to several key factors, including lengthy and complex informed consent forms, communication barriers between healthcare providers and study participants, and information that is not tailored to the specific population to be enrolled. These factors, individually or in aggregate, often lead to a lack of transparency in information provided to the study participants, such that they are unable to readily identify important information necessary to make a fully informed decision.

These key points are summarized in detail below.

1. Gaps in practice. Despite substantial research and new FDA guidance, real-world informed consent processes often fail to meet the standards established in the literature, speakers at the meeting said. They expressed concern that the gap remains a “significant challenge” in improving participant comprehension and engagement. FDA has taken several measures in recent years to address this gap, including issuing a proposed rule in 2022, which suggested key information to be provided at the start of informed consent documents, aiming to facilitate more meaningful discussions between health care providers and clinical trial participants; we summarized that proposal online here. Although the proposed rule has not been finalized, FDA later released draft guidance explaining how the rule may be implemented effectively. In 2023, FDA issued updated guidance emphasizing the importance of using varied media and simplified language (low-grade reading levels) to improve understanding, especially for diverse patient populations, which we discussed online here.

2. Using a patient-centric approach. A critical point raised during the meeting was the need for a patient-centric approach to informed consent. The goal is not merely to present technical language in a structured document, but to communicate in a way that fosters actual understanding. Although patient-centric materials can improve participant engagement and comprehension, developing such materials may require additional resources and time. The challenge here is incentivizing industry adoption, as these additional materials come with costs and regulatory hurdles, including institutional review board (IRB) approval.

3. Challenges with improving adherence to best practices. A major challenge in improving adherence to FDA guidance is ensuring that the informed consent process is both comprehensive and accessible. This can involve creating supplemental materials beyond the consent document itself, which can be resource-intensive for trial sponsors. Encouraging industry uptake of these practices remains difficult due to the added costs and logistical burdens.

4. Accessibility and inclusivity in the consent process. Ensuring that informed consent processes are accessible to a wide range of participants was a central theme at the PEAC meeting. Speakers discussed how this involves:

• Disability considerations: Developing pathways for participation that are inclusive of individuals with disabilities, and ensuring that all audiovisual and other materials are accessible. For example, hard copy informed consent forms may not work for visually impaired participants, but using a screen reader for electronic forms may be helpful. Additionally, wet signature requirements may be challenging for participants who have dexterity issues. For these reasons, electronic forms are generally preferable.
• Rural communities: Implementing outreach efforts to rural communities that account for varying technical capabilities and involve partnerships with local organizations to reach participants.
• Cultural competency: Ensuring that consent documents and materials resonate with individuals from diverse backgrounds, including variations in age, culture, gender, sexual orientation, race, and ethnicity. This is crucial for improving the diversity of clinical trial participants.

Informed consent form best practices

During the PEAC meeting, the presenters discussed several best practices for creating effective informed consent documents. These recommendations align with FDA guidance, but also go beyond compliance mandates to target enhanced patient comprehension and engagement.

• Essential informed consent form provisions: Forms should include sections explaining why participants should consider joining the trial, whom to contact with follow-up questions or concerns, and a clear description of post-trial considerations, including any medical care needed after the trial. Speakers at the meeting also recommended that the consent form should ideally also include the following elements:

  • Summaries: Providing brief summaries at both the beginning and end of the document to reinforce the key points.

  • Headings in the form of questions: Framing headings as questions can help structure the information in a participant-friendly way.

  • More bullet points and white space: Utilizing these methods can avoid overwhelming the participant with dense text.

  • Visual aids: Including diagrams, pictures, and illustrations where appropriate to help participants better understand complex information.

  • Translations: Making the document available in the primary languages of the participants.

  • “Key Information Section”: FDA’s 2024 draft guidance suggests including a “key information section” at the beginning of informed consent forms, which should cover:

    • Voluntary consent statement: Explicit declaration that involvement in the research study is voluntary and subjects can choose not to participate.
    • Study details: Clear explanation of the trial, “expected duration,” and the procedures involved.
    • Risks and benefits: Honest assessment of the potential “risks and discomforts,” as well as any benefits.
    • Alternatives: Description of available alternative treatments and how the trial differs from routine care.
    • Compensation and costs: Explanation of compensation for trial-related injury and any costs the participant might bear.

• Use of electronic and visual media: Sponsors may consider providing informed consent using various formats, such as videos and animations to explain complex procedures or risks in an engaging way, or interactive online formats where participants can ask questions and receive clarification.

• Effectively communicating informed consent: Informed consent is an ongoing process, not a one-time event. The participant should feel empowered to ask questions at any stage of the trial. Study sponsors should consider using clear and concise language, with active voice wherever possible, to avoid confusion. Additionally, study sites should consider which clinical team member is best suited to communicate with participants, noting that research coordinators (who are often trained in communication) may be more effective than principal investigators (who focus on the technical aspects of the study). Participants should receive a structured informed consent with a clear format that encourages ongoing discussions between the participant and the trial staff.

• Patient community input: While garnering feedback from study sponsors and investigators is meaningful in deciding what information is important for patients to consider, this input should not be considered unilaterally. Rather, it is imperative to involve patients, as a collective, early on in the process to help determine what information is most critical. This also helps to ensure that the process remains ethical and is tailored to the patient population(s) relevant to the study research conducted.

• Measuring comprehension: The effectiveness of informed consent should be gauged by the participant’s understanding. This can be accomplished by using pre-written questions or quizzes to assess comprehension, or encouraging participants to demonstrate their understanding and prompting a dialogue to fill any gaps in their knowledge.

Special considerations for medical devices

For studies involving medical devices, particularly those with long-term or permanent implants, the informed consent process may prompt additional considerations to better aid patients in understanding their overall role and burden as trial participants:

• Post-trial period: The consent process should generally address the post-trial period, where participants may need ongoing care or follow-up–which is especially important for device trials.
• Explantation: If the device is implantable, the form should explain whether it is explantable or will remain in the participant long-term.
• Interoperability: The form may need to clarify if there are any potential interoperability issues of which the participant should be aware (as used here, interoperability refers to the ability to safely, securely, and effectively exchange and use information among one or more devices).
• Data collection: The form may need to specify whether the device is collecting real-time data during the trial and how that data will be used.
• Post-trial support: Participants should be provided with long-term contact information for support if the device malfunctions, needs maintenance, or requires explantation.
• Longitudinal information: Information crucial for decision-making about whether to join a trial may differ from what is necessary for ongoing participant engagement in the study and compliance with study-related tasks. Careful calibration is needed to balance initial consent with periodic updates to participants during and after the study to maintain their engagement as needed.