The FDA issued a final rule Dec. 20 that harmonizes its regulations regarding the waiver of informed consent with the revised Common Rule and the mandates of the 21st Century Cures Act. The rule is effective Jan. 22, 2024.

The FDA had required informed consent before a subject could participate in a clinical investigation, and only allowed an exception in certain life-threatening situations, by presidential waiver for certain military operations, or for emergency research.

The new rule provides an exception from the requirement to obtain informed consent when a clinical investigation poses no more than minimal risk to the people participating in the research, and the research includes appropriate safeguards to protect the rights, safety and welfare of participants.

“FDA is issuing this final rule to permit an IRB waiver or alteration of informed consent in limited circumstances, consistent with the Cures Act,” the FDA said. “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.”

The FDA also noted “the Common Rule’s provisions for waiver or alteration of informed consent for minimal risk research have been in effect for over 30 years and have provided appropriate safeguards to protect the rights and welfare of human subjects.”

“We anticipate this new rule will enable minimal risk research that would not be practicable to conduct otherwise,” said FDA Commissioner Robert Califf, in announcing the new regulation. “This could include studies comparing the effectiveness of approved products to determine which option works best for certain patients. Studies conducted with a waiver or alteration of informed consent under this final rule could result in more treatment and diagnostic options without compromising the rights, safety and welfare of people participating in those studies.”

Under a new 21 C.F.R. §50.22, institutional review boards (IRBs) “may approve an informed consent procedure that does not include or that alters some or all of the elements of informed consent set forth in 21 C.F.R. §50.25(a) and (b), or may waive the requirement to obtain informed consent, provided the IRB finds and documents”:

• The clinical investigation involves no more than minimal risk to the subjects;
• The clinical investigation could not practicably be carried out without the requested waiver or alteration;
• If the clinical investigation involves using identifiable private information or identifiable biospecimens, the clinical investigation could not practicably be carried out without using such information or biospecimens in an identifiable format;
• The waiver or alteration will not adversely affect the rights and welfare of the subjects; and
• Whenever appropriate, the subjects or legally authorized representatives will be provided with additional pertinent information after participation.

“This rule harmonizes FDA’s requirements for waiver or alteration of informed consent for minimal risk clinical investigations with the revised Common Rule’s requirements under 45 C.F.R. §46.116(f)(3),” the FDA said in the preamble to the final rule (88 Fed. Reg. 88228).

The FDA expects there to be costs and benefits from the change. “We expect costs in the form of affected IRBs, as well as investigators and sponsors of clinical investigations, reading and learning the rule. We also expect costs in the form of drafting new waiver or alteration requests and additional recordkeeping burdens associated with reviewing and documenting IRB decisions on waiver or alteration requests,” the agency said.

However, the FDA also expects “there will be cost savings to IRBs from harmonization of FDA’s informed consent regulations with the provision for waiver or alteration of informed consent for certain minimal risk research in the Common Rule,” the agency said. “We also expect benefits in the form of healthcare advances from minimal risk clinical investigations that would not be performed without a waiver or alteration of informed consent.”