FDA Issues Proposed Guidance: Institutional Review Boards,
Clinical Investigators, and Sponsors: Exception from
Informed Consent Requirements for Emergency Research

By Loni Eustace-McMillan, J.D., LL.M. Candidate

On March 30, 2000, the Food and Drug Administration (FDA) announced publication of its proposed Draft Guidance for Institutional Review Boards, Clinical Investigators, and Sponsors: Exception From Informed Consent Requirements for Emergency Research. 61 Fed. Reg. 16,923 (2000). This draft guidance addresses several areas contained in final regulations published by the FDA, effective November 1, 1996. These regulations allowed a waiver of the requirement of obtaining and documenting informed consent from human subjects to facilitate critical care investigators in conducting emergency research. The waiver of informed consent is limited and is available only under certain conditions. The FDA's final regulations, their background, and comments are set forth in Protection of Human Subjects; Informed Consent, 61 Fed. Reg. 51,498 (1996).

The Waiver of Informed Consent Requirements in Certain Emergency Research strictly limit conditions under which the waiver may be granted. The regulations require the responsible Institutional Review Board (IRB) to have approved both the research activity and the waiver of informed consent in accordance with the provisions set forth in the final rule. The main requirements of the final rule (codified at 21 C.F.R. § 50.24) are: (1) the patient has a situation that is life threatening and treatments available are either unproven or unsatisfactory; (2) obtaining the patient's informed consent is not feasible due to their medical condition and the necessity to begin treatment before consent can be obtained from their legally authorized representative; (3) the research holds the possibility of directly benefiting the patient; (4) the clinical investigation could not be carried out practicably absent the waiver; (5) the risks and benefits of the research are considered reasonable in light of both the condition of the patient and the risks and benefits of the existing standard therapy for the condition.

In conjunction with narrowly restricting the conditions under which an informed consent waiver may be granted for emergency research, the final regulations contain other provisions aimed at protecting the rights and welfare of the patients (research subjects). These protections include:

(1) community consultation with representatives of the communities in which the research will be conducted;

(2) community consultation with the communities from which the research subjects will be drawn;

(3) public disclosure to the communities in which the clinical investigation will be conducted and from which the subjects are to be drawn, both prior to the initiation of the clinical research and following completion of the clinical research, in order to apprise the communities and researchers of the study itself, of the demographic characteristics of the research population, and of the research results;

(4) the establishment of a data monitoring committee which is independent from the IRB for overseeing the clinical investigation; and

(5) in the event obtaining informed consent is not feasible and a legally authorized representative is not reasonably available, the investigator, if feasible, has committed to trying to contact a family member of the subject, who is not a legally authorized representative, during the therapeutic window and asking the family member whether he or she objects to the subject's participation in the clinical research -- these efforts to contact family members are to be summarized and made available to the IRB. 21 C.F.R. § 50.24.

Following the implementation of the final regulations, the FDA continued to review and monitor the methods being used to implement the regulations. A year after their implementation a meeting was held by the FDA to facilitate discussion as to how the regulations were working. As a result, the FDA made a determination that guidance was needed to aid in proper implementation of various requirements contained in the final regulations.

The draft guidance document addresses provisions in the final regulations which are meant to provide additional protection to the vulnerable population of people who are possible subjects for research involving the waiver of informed consent. This population includes individuals with life-threatening conditions who are unable to give informed consent and who are unable to actively refuse their enrollment in the research project.

The draft guidance deals with several areas of concern, particularly the requirements of community consultation, public disclosure activities, and the establishment of procedures to obtain informed consent, when feasible. Other areas are also addressed, such as: the use of data monitoring committees; the requirement for concurrence by a licensed physician; utilization of independent IRBs; and efforts made to contact a legally authorized representative for the subject, or a family member, regarding the subject participating in the research project, as well as documentation of these efforts.

Additionally, the draft guidance explains when clinical investigations requesting an exception of informed consent requirements for emergency research may not be undertaken. It also provides definitions for key terms used in the final regulations and the draft guidance document.

A copy of this draft guidance can be obtained via the Internet at http://www.fda.gov/ora/compliance_ref/bimo/. The deadline for submission of written comments is May 30, 2000.

04/11/00