Expediting clinical trials that post minimal risk is important to advance healthcare & drug development. In particular, easing the requirements for informed consent regarding trial participants- for minimal risk clinical trials- can help expedite the entire clinical development process and ultimately accelerate the overall regulatory approval process.
Earlier the US FDA’s regulations allowed for exceptions related to informed consent in certain cases i.e., life threatening situations or when certain emergency requirements are met. However, more recently, the US FDA released a final rule in which International Review Boards (IRBs) could waive or amend informed consent provided a certain criterion was met. This rule safeguards the trial participants rights, safety, and welfare and enables minimal risk clinical investigations to advance healthcare advances. This rule, which will go into effect in January 2024, is aimed at harmonising the FDA’s human participant regulations with the US Department of Health and Human Services.
Five Criteria for consideration by IRB
The finalised rule outlines five criteria for IRBs to consider when deciding whether 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.
Key Amendments and New Sections
The FDA added a new section to its regulations titled “Exception from informed consent requirements for minimal risk clinical investigations.” This edition includes three amendments to existing sections to align with the exception of informed consent for certain minimal-risk clinical investigations. A notable addition is the new criterion, addressing clinical investigations involving identifiable private information or biospecimens.
Costs and Benefits
Anticipated costs associated with the rule include impacts on IRBs, investigators, and sponsors who will need to familiarise themselves with the new regulations. Costs also involve drafting new waiver or alteration requests and additional recordkeeping burdens related to reviewing and documenting IRB decisions. The estimated net present value of the costs is around $10.1 million, with potential savings of approximately $1.7 million for IRBs due to harmonisation with the Common Rule.
Expected benefits include healthcare advances resulting from minimal-risk clinical investigations that may not proceed without the waiver or alteration of informed consent. However, quantifying these benefits is challenging due to insufficient data on the specific focus of such studies for regulatory submissions to the FDA.
Public Comments and FDA Response
The FDA received fewer than 50 public comments on the proposal, with general support for the changes to harmonise human participant protection regulations and reduce administrative burdens related to informed consent. Some concerns were raised regarding international standards, such as the Nuremberg Code and the Declaration of Helsinki, but the FDA argued that the waiver is only permitted in circumstances of minimal risk, and IRBs must ensure it does not adversely affect subjects’ rights and welfare.
Despite concerns, the FDA chose to adopt all five criteria in the final rule, aiming for better harmonisation with the HHS revised Common Rule. The agency plans to issue guidance to assist IRBs in applying these criteria and anticipates that this harmonisation will reduce administrative burdens and research costs. Additionally, the FDA clarified that it would not revise the definition of minimal risk and would not impose a new process on IRBs for documenting waiver or alteration decisions, as they are already inspected to ensure compliance with FDA regulations.
The FDA’s finalised rule facilitates minimal-risk clinical investigations by allowing exceptions to the informed consent requirement. As the rule comes into effect in 2024, it will be essential for stakeholders to navigate the new criteria and guidelines to benefit from the anticipated reduction in administrative burdens and research costs.
In addition to regulatory and pharmacovigilance services for global customers, DDReg also provides support for clinical regulatory services for compliant and efficient trial management. This includes submission of clinical trial application packages to global authorities. Read more about clinical investigations from the experts themselves: Streamlining Clinical Investigations for Medical Devices.