By Melinda Young, Author

The FDA has issued a proposed rule that some say would provide research institutions with much-needed clarity on informed consent regulations and open the door to clinical breakthroughs.

“I think, personally, anything that is on the side of loosening up the asinine, ambiguous rules is wonderful,” says Susan Rose, PhD, executive director of the office for the protection of research subjects at the University of Southern California in Los Angeles.

Current FDA regulations allow informed consent waivers only in life-threatening situations or during certain emergency research.1 But with the 2016 passage of the 21st Century Cures Act, the agency was given the ability to grant exceptions for clinical investigations that pose no more than minimal risk to human subjects and that include safeguards.

The proposed rule, issued in November 2018, would implement Cures Act requirements, more closely aligning the FDA’s informed consent waiver provisions with related provisions in the Common Rule. The agency’s leader says such change could bring about research innovation.

FDA commissioner Scott Gottlieb, MD, said in a statement announcing the proposed rule that the agency had “received feedback from sponsors and investigators that they were not able to move forward in conducting important clinical investigations where there would be minimal risk.”

Gottlieb said that the proposed change could enable research “addressing significant public health needs without compromising the rights, safety, or welfare of human subjects.”

Regulatory uniformity may be another benefit.

“I think the steps the FDA is [taking] right now are useful,” says Rose. “It’s a good thing if a study is compliant and ethical and the IRB has looked at it and waivers are involved — unless another government agency doesn’t allow the same thing.”

That point also is emphasized by James Riddle, MCSE, CIP, CPIA, CRQM, executive vice president of Kinetiq, a division of Quorum IRB, in Seattle.

“For many years, we’ve had one set of regulations from the Office for Human Research Protections [OHRP] from the Common Rule and another from the FDA, and there were places where the two of them did not match,” he says.

“IRBs and researchers do struggle with how to handle consent and consent activities for FDA-regulated data research — under OHRP, the old rules were you could waive consent, and under FDA, the rule was the intent to exercise enforcement discretion,” Riddle says.

With the FDA’s proposed rule, IRBs would be allowed to waive or alter certain informed consent elements or waive informed consent altogether — a significant departure from the agency’s current system.

These changes would give IRBs a consistent way to approach waivers — with one big exception, Riddle says.

“FDA chose to harmonize against existing OHRP regulations but did not harmonize against the new Common Rule that goes into effect on Jan. 21, 2019,” he explains. “The FDA adopted four waiver-of-consent criteria that exist in the [old] Common Rule regulations; the new Common Rule includes five waiver-of-consent criteria.”

Under the FDA’s new approach, informed consent is waived when IRBs find and document the following:

• the clinical investigation involves no more than minimal risk to the subjects;

• the waiver or alteration of informed consent will not adversely affect the rights and welfare of the subjects;

• the clinical investigation could not practicably be carried out without the waiver or alteration of informed consent;

• whenever appropriate, the subjects will be provided with additional pertinent information after participation.

And this is the fifth criterion that will be in the new Common Rule — but would not be adopted by the FDA: “If the research involves using identifiable private information or identifiable biospecimens, the research could not practicably be carried out without using such information or biospecimens in an identifiable format.”

There is no information about why the FDA chose not to adopt the fifth criterion, which would have made harmonization more complete, Riddle says. “We look forward to additional guidance from FDA, or we hope they’ll clarify,” he adds.

From a practical standpoint, informed consent waivers will not be appropriate for most FDA-regulated research but could be helpful in certain instances, Riddle notes.

“While it’s nice to see the FDA harmonizing, this is the low-hanging fruit for them,” he says.

“The underlying theme is it is great the FDA is doing the harmonization; it will facilitate more research, and it will reduce burden on IRBs on how to deal with a waiver of informed consent when a regulatory structure didn’t exist for the FDA, and now it does.”

The FDA will accept comments on the proposed rule through Jan. 14, 2019.


1. Institutional Review Board Waiver or Alteration of Informed Consent for Minimal Risk Clinical Investigations. Fed Reg. 2018;83(221):57378-57385.