FDA eases informed consent requirements for minimal risk trials

The US Food and Drug Administration (FDA) finalized a rule allowing Institutional Review Boards (IRBs) to waive or alter elements of informed consent for certain clinical trials that pose minimal risk to human subjects.

The rule, published on 21 December 2023, finalizes a proposal the agency issued in 2018 and implements provisions of the 21^st Century Cures Act that gave FDA the authority to allow an informed consent exception for minimal risk clinical testing that includes human subjects safeguards and directed FDA and the US Department of Health and Human Services to harmonize their human subjects regulations (RELATED: FDA Proposes Changes to Informed Consent Rules, Regulatory Focus 13 November 2018).

Under FDA’s current regulations, informed consent exceptions are only allowed in certain cases, such as life-threatening situations, when certain emergency research requirements are met, and with a Presidential waiver for specific military operations. In 2017, the agency issued guidance advising informing and research sponsors that it would not object to waiving or altering informed consent requirements for certain minimal risk clinical trials. The FDA plans to withdraw the 2017 guidance once the final rule goes into effect in January 2024.

“We believe that this rule will both safeguard the rights, safety, and welfare of human subjects and enable minimal risk clinical investigations that may facilitate medical advances and promote public health. In addition, because some clinical research is subject to FDA and other federal requirements under the Common Rule, harmonization of this waiver provision should also provide clarity for and reduce burden on the research community,” FDA wrote in the final rule.

Final rule provisions

The rule finalizes five criteria for IRBs to waive or alter informed consent:

The clinical investigation involves “no more than minimal risk” to research subjects.
Waiving or altering informed consent will not adversely impact the rights and welfare of participants.
The investigation could not be practicably carried out without the waiver or alteration of informed consent.
When appropriate, participants are provided with additional relevant information after participation in the investigation.
For research involving identifiable private information or identifiable biospecimens, the research could not be practicably carried out without using the information or biospecimens in an identifiable format.

The proposed rule included the first four criteria but held back on including the provision related to identifiable private information and biospecimens to receive public comment. FDA noted that few commenters opposed including the fifth criterion, though some expressed concerns that the agency had not defined the terms “identifiable private information” and “identifiable biospecimen” and that they could change over time. Other commenters suggested that the fifth criterion was unnecessary.

FDA officials ultimately chose to adopt the fifth criterion in the final rule to better harmonize with the HHS revised Common Rule. “We expect that this harmonization will reduce administrative burdens on IRBs and researchers and reduce research costs,” FDA wrote in the final rule.

The agency also said it planned to issue guidance to aide IRBs in applying the criteria for waiving or altering informed consent requirements. “In that guidance, we intend to provide additional information on the types of FDA-regulated minimal risk clinical investigations that we anticipate would satisfy the criteria for a waiver or alteration of informed consent,” the agency wrote.

Comments on the proposed rule

The agency received fewer than 50 public comments on the proposal. A majority of the general comments were in favor of the proposed changes to harmonize human subjects protection regulations and reduce administrative burdens related to informed consent. However, some comments wrote that waiving informed consent conflicted with international standards, including the Nuremberg Code, the Declaration of Helsinki, and the International Covenant on Civil and Political Rights. FDA disagreed that the informed consent rule was in violation of the spirit of those standards.

“The waiver is only permitted in circumstances where the risks posed to subjects by the research are minimal and where an IRB has reviewed the research and determined, among other things, that the waiver or alteration will not adversely affect the rights and welfare of subjects. If research can be practicably carried out without a waiver of informed consent, investigators cannot obtain a waiver under this rule,” the agency wrote.

Some comments on the criteria for waiving or altering informed consent expressed concerns that the “minimal risk” threshold was too vague and could be misused, while some comments suggested that IRBs should not be the ones to make minimal risk determinations.

FDA noted in the final rule that it was not revising the definition of minimal risk since doing so would risk confusion in the research community.

“Because of the longstanding consistency in the definitions of minimal risk provided in both FDA regulations and the Common Rule, IRBs have experience in applying the term ‘minimal risk’ to research involving human subjects, including determining when a clinical investigation involves no more than minimal risk,” FDA wrote in the final rule.

FDA also declined to impose a new process on IRBs to document waiver or alteration decisions for a clinical investigation since FDA already inspects IRBs to ensure they are following FDA regulations when approving and reviewing research.

Federal Register Notice

FDA eases informed consent requirements for minimal risk trials

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