In accordance with medical ethics regarding research on human subjects and federal regulatory requirements, it is necessary to obtain informed consent (IC) from prospective clinical trial participants. Required elements of IC in health research governed by U.S. Federal Regulations, including FDA regulations and the Common Rule, are clearly described, yet the current IC process is often not meeting the needs of research participants. Informed consent documents (ICDs) are lengthy and may be difficult for patients to comprehend. Institutionally-required legal language is often inserted into ICDs, creating confusion about whether the ICD’s purpose is to clearly inform the patient or to serve institutional needs. Various groups have taken measures to address these concerns, but deficiencies with the process still exist. Issues surrounding re-consent of research participants, as well as when consent is required in a learning system of health care, are related issues but are outside the scope of this project.

Informed Consent (2013-2016)

• Identify previous and current efforts to improve ICDs and the IC process, including alternatives to the traditional paper ICD
• Describe barriers and propose potential remedies to concisely communicating the required elements of IC
• Propose a more effective process, including IC documentation, for ensuring research participants’ understanding of critical IC elements, taking into account variability among research settings and participants

Completion of the CTTI Informed Consent project will lead to a higher quality IC process. Application of the corresponding recommendations may lead to the following improvements:

• The IC process may be more interactive, customized, and transparent to meet the needs of individual study participants.
• Trial staff can benefit from better training tailored to their needs and learning styles, and patients can benefit from more emotionally responsive trial staff.
• The ICD can be restructured to increase readability, enhance trial participant understanding of the study, and provide additional information that is easily accessible.
• Electronic consent systems may be considered to facilitate use of the improved ICD and consent participants.

• Literature review
• Stakeholder interviews
• Expert meeting

Evidence from the literature review suggests that IRB-, sponsor-, and site-related operational barriers exist, along with an inadequate understanding of what patients want from the IC process. No single proven tool for measuring the quality of IC or effectiveness of consent interventions was cited in the literature. Limited, available evidence suggests that the current consent process has direct consequences on the ability to conduct clinical trials. The analysis of the literature review was published in May 2016. The published results from the expert interviews supported these literature review findings and expanded on identified barriers.

All interviewees agreed that IC is essential to the protection of research participants; however, most acknowledged that the IC process in the United States has evolved into a rigid and cumbersome process that requires immediate attention and reform. Interviewees expressed consensus on three major themes: a new approach to the ICD, enhancing participant understanding of the clinical research, and modification of IRB review.

Some barriers that result in lengthy, variable, and overly complicated ICDs include the following:

IRB-related:

• Lack of accepted readability standards
• Local IRB review of ICDs in multisite trials
• Varying interpretations of regulations
• Inadequate training in plain language practices for IRB staff

Sponsor-related:

• Challenging legal language added to ICDs to reduce liability

Staff-related barriers to a successful IC process tend to more commonly result in participant dissatisfaction due to unmet emotional needs or lack of relevant trial information. These barriers include:

• Disconnection between expectations and reality of IC discussions
• Staff de-emphasizes importance of the information to the participant
• Pressure to meet enrollment targets shifts focus away from participants and leads to rushed interactions

To address these barriers, experts explored new approaches to the IC process that focused on enhancing trial participant understanding. The most frequent recommendation for a single actionable change was to reform the ICD required for federally regulated research by making it simpler, shorter, and more understandable. Following this, interviewees proposed multiple strategies to create a more interactive and ongoing IC process to enhance research participant understanding. Some strategies include improving staff training on the conduct of an IC discussion, allowing adequate time and selecting the appropriate setting for the discussion, and providing an opportunity for prospective research participants to speak with other participants as a resource for information. Evaluating participants’ understanding was another topic that experts discussed during the interview. Several interviewees proposed that research participants’ comprehension about the clinical investigation be evaluated. A third consensus issue from the interviews was the need for modification of practices in IRB review of clinical research. Aligned with recommendations from the CTTI Single IRB projects, the most substantive expert recommendation was implementation of a single IRB of record for multisite clinical trials.

Current Relevant FDA and DHHS Regulations:

FDA Regulations are detailed in 21 CFR, Part 50 (Informed Consent of Human Subjects). 50 Subpart B sections on informed consent of human subjects include:

• 50.20 - General requirements for informed consent
• 50.23 - Exception from general requirements
• 50.24 - Exception from informed consent requirements for emergency research
• 50.25 - Elements of informed consent
• 50.27 - Documentation of informed consent

DHHS regulations are detailed in 45 CFR, Part 46 (Protection of Human Research Subjects). 46 Subpart A sections on informed consent include:

• 46.116 - General requirements for informed consent
• 46.117 - Documentation of informed consent

NIH Collaboratory:

• View the NIH Collaboratory's free resources on informed consent.
• View a moderated discussion on the HHS Public Meeting Related to Protection of Human Subjects and Standard of Care Research.

Organization affiliations are listed as active affiliations during the project.

*Indicates former project manager, team leader, or team member.