Key Takeaways

• The FDA issued “Informed Consent Guidance for IRBs, Clinical Investigators, and Sponsors” that supersedes its 1998 guidance and finalizes its 2014 guidance.
• The guidance outlines the primary components of informed consent and the roles and responsibilities of IRBs, clinical investigators, sponsors and the FDA itself in the informed consent process.
• The FDA dedicated a section of the guidance to FAQs covering a wide range of informed consent-related questions.

On Aug. 15, the Food and Drug Administration (FDA) issued new guidance aimed at assisting institutional review boards (IRBs), clinical investigators and sponsors in complying with the FDA’s informed consent requirements for clinical investigations. The FDA’s informed consent requirements are set forth in the FDA’s regulations on the Protection of Human Subjects (21 CFR Part 50). 21 CFR Part 50 “applies to all clinical investigations regulated by the FDA under sections 505(i) and 520(g) of the Federal Food, Drug, and Cosmetic Act, as well as clinical investigations that support applications for research or marketing permits for products regulated by the FDA, including foods, including dietary supplements, that bear a nutrient content claim or a health claim, infant formulas, food and color additives, drugs for human use, medical devices for human use, biological products for human use and electronic products.” This guidance supersedes the FDA’s 1998 guidance, “A Guide to Informed Consent,” and finalizes its 2014 guidance, “Informed Consent Information Sheet.” The full guidance document is available online here.

The FDA explains in the guidance that informed consent is more than obtaining a signature; it is a process that includes facilitating the prospective subject’s understanding of the relevant clinical investigation information, providing adequate opportunity for the prospective subject to ask questions and consider whether to participate, obtaining the prospective subject’s voluntary agreement to participate, and continuing to provide information as the clinical investigation progresses or the situation requires.

Guidance on the regulatory requirements for informed consent

Along with outlining general informed consent requirements per 21 CFR Part 50.20, the FDA identifies exceptions to the requirement for informed consent, provides considerations to minimize the possibility of coercion or undue influence, explains the need for information to be understandable by a prospective subject or the legally authorized representative, and discusses the prohibition on exculpatory language in the consent process.

The FDA also highlights the basic elements of informed consent, including a requirement to describe the clinical investigation and the extent of the prospective subject’s participation – potential risks and discomforts, an explanation of benefits, disclosing alternatives and maintaining confidentiality – describe injury compensation, and provide information on whom to contact with questions and a statement that participation is voluntary, as well as several other elements to consider (e.g., unforeseeable risks, involuntary termination, additional costs to subjects), when appropriate.

The guidance further explains that subjects enrolled in “applicable clinical trials” must be notified during the informed consent process that information has been or will be submitted for inclusion in the clinical trial registry databank under paragraph (j) of Section 402 of the Public Health Service Act. It also provides elements of appropriate documentation of informed consent along with alternative methods of obtaining informed consent.

Roles of IRBs, clinical investigators and sponsors

The FDA believes that IRBs, clinical investigators and sponsors share responsibility for ensuring that the informed consent form and process are adequate and meet the FDA’s regulatory requirements. The FDA notes in its guidance that the regulatory requirements represent the minimum information to be provided to prospective subjects for informed consent and that the consent form should also incorporate any additional information that may affect subjects’ rights and welfare or willingness to participate in the clinical research.

The FDA explains that the IRB is responsible for reviewing and approving consent forms that comply with applicable regulatory requirements and offers guidance on IRB review of informed consent materials, the consent process and continuing review of new information or changes to the clinical investigation. The guidance clarifies that the IRB has ultimate responsibility to determine whether subjects must be informed of certain financial arrangements.

Clinical investigators are similarly tasked with ensuring that effective informed consent is obtained from subjects as well as with protecting the rights, safety and welfare of subjects during the clinical investigation. The finalized guidance outlines considerations for clinical investigators, including the process for delegation of the consent discussion and the extent to which clinical investigators should disclose financial relationships or interests.

The FDA also includes guidance for sponsors on the use of model consent forms. The FDA guidance outlines how sponsors should handle substantive modifications to consent forms for multicenter clinical investigations. It further indicates that informed consent forms should describe the activities for which sponsor personnel will be present.

Insights into FDA review of informed consent materials

The FDA included in its guidance an explanation of its own responsibilities with respect to the review of informed consent forms. Specifically, the FDA outlined the factors that it considers when reviewing consent forms for investigational new drugs and biologics and for investigational medical devices.

The Q&A

The FDA dedicated a section of the guidance to answering frequently asked questions. Many questions were dedicated to considerations and protections for enrolling children, non-English speakers, those with low literacy and numeracy, and those with physical or sensory disabilities or impaired consent capacity. The FDA also addressed questions regarding who can serve as a legally authorized representative, electronically obtained informed consent, simultaneous participation in more than one clinical investigation, handling data when a subject withdraws, sharing new information with subjects and whether informed consent is required to review patient records.

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