New FDA Guidance on Informed Consent Waiver for Clinical Investigations Involving No More than Minimal Risk

FDA issues guidance for immediate implementation- IRB Waiver or Alteration of Informed Consent for Clinical Investigations Involving No More Than Minimal Risk to Human Subjects

Author: Patricia Garcia, Regulatory Consultant, Late Stage, Clinical Division, Inventiv Health Clinical Spain S.L.

In July 2017, FDA issued this guidance for immediate implementation.

Link to the Guidance: https://www.fda.gov/downloads/RegulatoryInformation/Guidances/UCM566948.pdf

The document provides guidance to sponsors, investigators, and institutional review boards (IRBs) on enforcement of FDA regulations governing informed consent requirements for clinical investigations that involve no more than minimal risk to human subjects.

Minimal risk is defined in applicable FDA regulations as “the probability and magnitude of harm or discomfort anticipated in the research are not greater in and of themselves than those ordinarily encountered in daily life or during the performance of routine physical or psychological examinations or tests.” (21 CFR 50.3(k), 56.102(i)).

In this guidance, it is stated that  FDA doesn´t have any intention to object to any waiver or alteration for informed consent requirements  from an IRB for certain minimal risk clinical investigations.  In addition, FDA does not intend to object to a sponsor initiating, or an investigator conducting, a minimal risk clinical investigation for which an IRB waives or alters the informed consent requirements when:

  1. The clinical investigation involves no more than minimal risk (as defined in 21 CFR 50.3(k) or 56.102(i)) to the subjects;
  2. The waiver or alteration will not adversely affect the rights and welfare of the subjects;
  3. The clinical investigation could not practicably be carried out without the waiver or alteration; and
  4. Whenever appropriate, the subjects will be provided with additional pertinent information after participation.

Currently, FDA’s regulations governing the protection of human subjects (21 CFR parts 50 and 56) allow exception from the general requirements for informed consent only in life-threatening situations when certain conditions are met (21 CFR 50.23) or when the requirements for emergency research are met (21 CFR 50.24).

The objective of the guidance is to facilitate the conduct of studies that may contribute to the development of products to diagnose, treat or address unmet medical needs.

After 21st Century Cures Act (Cures Act) was signed in December 2016, FDA has obtained the authority to permit an exception from informed consent requirements when the proposed clinical testing poses no more than minimal risk to the human subject and includes appropriate safeguards to protect the rights, safety, and welfare of the human subject. Over the last years, FDA has been aware of inquiries from investigators about the difficulties to obtain consent in important clinical investigations with minimal risk.

FDA regulations and the Common Rule share the same definition for “minimal risk”. Moreover, in general FDA regulations for the protection of human subjects conform with the “Federal Policy for the Protection of Human Subjects” HHS (Common Rule) for the same matter with a few exceptions related to the differences in FDA’s mission or statutory authority.

The Common Rule permits an IRB to waive the requirements to obtain informed consent, or to allow changes to, or omission of, some or all elements of informed consent if the IRB finds and documents that:

(1) the research involves no more than minimal risk to the subjects;

(2) the waiver or alteration will not adversely affect the rights and welfare of the subjects;

(3) the research could not practicably be carried out without the waiver or alteration; and

(4) whenever appropriate, the subjects will be provided with additional pertinent information after participation. (45 CFR 46.116(d)).

In light of the Cures Act amendment to the FD&C Act, FDA intends to revise its informed consent regulations to add this waiver or alteration under appropriate human subject protection safeguards to the two existing exceptions from informed consent (i.e., in life-threatening situations and for emergency research). However, until FDA promulgates these regulations, FDA is issuing this guidance to demonstrate the intention of facilitating the conduct of clinical investigations with no more than minimal risk to human subjects.

FDA will consider any comments received and will revise the guidance when appropriate. Contact details for submitting comments or suggestion are described in the guidance.

This opens a door to reduce the requirements accordingly to a risk balanced management of each type of research in human subjects.

It seems that FDA is acting in line with what has been a discussion, over the last years, between a part of the research community in USA. As of 2015, some authors have published their thoughts related to the burden of requirements to some low risk clinical investigations, some of them specific to the informed consent requirements. For example:  Pragmatic Clinical Trials (PCTs).  For this type of study that is conducted with marketed drugs, there has been a claim for establishing a risk-based approach to obtaining informed consent that would facilitate the conduct of them without compromising the protection of subjects.

A number of national initiatives, including the Patient-Centered Outcomes Research Institute’s (PCORI),  National Patient Centered Outcomes Research Network (PCORnet) and the National Institutes of Health (NIH) Health Systems Research Collaboratory (Collaboratory), are catalyzing new infrastructures for PCTs and are developing ways that respect and protect the autonomy and privacy of research participants yet go beyond reliance on traditional informed consent.

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