The US Food and Drug Administration (FDA) recently proposed changes that would allow institutional review boards (IRBs) to waive or alter requirements for obtaining informed consent for certain clinical trials involving minimal risk to participants. FDA’s proposal is a significant deviation from current IRB informed consent requirements and could improve clinical trial efficiency for IRBs and clinical investigators involved in minimally risky clinical trials.
Current Regulations and Purpose IRBs
Under current FDA regulations, exceptions for obtaining informed consent can only be made in life-threatening situations or when conditions for emergency research are met. Outside those situations, FDA regulations require that subjects provide informed consent before they can participate in a clinical trial.
IRBs are legally responsible for the review, approval, and continuing review of clinical investigations.Of many responsibilities, IRBs must ensure clinical investigators appropriately obtain a study subject’s legally effective informed consent prior to the subject’s participation in a clinical trial. Currently, FDA permits IRBs to waive or alter informed consent requirements in only the following limited circumstances:
Emergency Use – Applies when human subjects: (i) have a life-threatening situation; (ii) have a severely debilitating condition; (iii) there is no standard acceptable treatment available for the subject’s condition; and (iv) there is insufficient time to obtain IRB approval;
Planned Emergency Research – Applies when human subjects: (i) have a life-threatening medical condition that necessitates urgent intervention; and (ii) cannot provide informed consent because of their condition. Additionally, the research must: (i) involve an investigational product that has the prospect of direct benefit to the patient and must be administered before informed consent can be obtained; and (ii) show there is no reasonable way to identify individuals eligible for participation;
In Vitro Diagnostic Device Studies Using Leftover Human Specimens who are not Individually Identifiable – This informed consent waiver process is subject to numerous requirements aimed at preserving the anonymity of the individual from whom the specimen was obtained; or
Armed Forces Personnel – Applies only if the President of the United States waives informed consent for military personnel for administration of an investigational product to members of the armed forces.
Proposed Rule
The proposed rule would defer to institutional review boards (IRBs) to make waiver decisions. To waive informed consent, IRBs must find:
- The research involves no more than minimal risk to the subjects;
- The waiver or alteration will not adversely affect the rights and welfare of the subjects;
- The research could not practicably be carried out without the waivers or alterations; and
- Whenever appropriate, the subjects will be provided with additional patient information after participation.
As the FDA Commissioner, Scott Gottlieb, M.D., explains:
Over the years, we’ve 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 as these trials involved situations where obtaining informed consent wasn’t possible, and the agency lacked the authority to permit a waiver of informed consent for that research. With the passage of the 21st Century Cures Act, the FDA’s authorities were changed, allowing greater flexibility. That’s why today, we’re proposing a change to our informed consent regulations in a way that maintains safeguards to protect study participants, while allowing important research to proceed where there is minimal risk to patients.
So many questions…. Who defines minimal risk or is there already a definition? Who decides if an adverse event following administration is related or unrelated? I certainly hope that minimal risk does not include death, severe disability, long-term health issues following administration, no matter how small a percentage of study participants might encounter these adverse effects. How is the loop closed such that study trial moves from the realm of minimal risk to greater risk and therefore loses the waiver when serious adverse effects are encountered? And, who populates these IRBs? Will they include citizen stakeholders or will they all be from industry?