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PER.1 Organization Policy on Planned Emergency Research and Requirements for Waiver of Consent in Planned Emergency Research 21 CFR 50.24; DHHS Emergency Research Consent Waiver

December 2020

The Organization allows the IRBs to review research activities that plan to enroll human subjects in research that will be conducted in an emergency situation in which consent cannot be obtained from subjects due to their medical condition and cannot be obtained by a subject’s legally authorized representative.

Planned emergency research under a waiver of consent may be conducted under either FDA regulations (21 CFR 50.24) or the DHHS Common Rule (Secretarial waiver pursuant to authority granted under 45 CFR 46.101(i)).  In either case, the requirements are as follows:

(a) The IRB responsible for the review, approval, and continuing review of the clinical investigation described in this section may approve that investigation without requiring that informed consent of all research subjects be obtained if the IRB (with the concurrence of a licensed physician who is a member of or consultant to the IRB and who is not otherwise participating in the clinical investigation) finds and documents each of the following:

(1) The human subjects are in a life-threatening situation, available treatments are unproven or unsatisfactory, and the collection of valid scientific evidence, which may include evidence obtained through randomized placebo-controlled investigations, is necessary to determine the safety and effectiveness of particular interventions.

(2) Obtaining informed consent is not feasible because:

(i) The subjects will not be able to give their informed consent as a result of their medical condition;

(ii) The intervention under investigation must be administered before consent from the subjects' legally authorized representatives is feasible; and

(iii) There is no reasonable way to identify prospectively the individuals likely to become eligible for participation in the clinical investigation.

(3) Participation in the research holds out the prospect of direct benefit to the subjects because:

(i) Subjects are facing a life-threatening situation that necessitates intervention;

(ii) Appropriate animal and other preclinical studies have been conducted, and the information derived from those studies and related evidence support the potential for the intervention to provide a direct benefit to the individual subjects; and

(iii) Risks associated with the investigation are reasonable in relation to what is known about the medical condition of the potential class of subjects, the risks and benefits of standard therapy, if any, and what is known about the risks and benefits of the proposed intervention or activity.

(4) The clinical investigation could not practicably be carried out without the waiver.

(5) The proposed investigational plan defines the length of the potential therapeutic window based on scientific evidence, and the investigator has committed to attempting to contact a legally authorized representative for each subject within that window of time and, if feasible, to asking the legally authorized representative contacted for consent within that window rather than proceeding without consent. The investigator will summarize efforts made to contact legally authorized representatives and make this information available to the IRB at the time of continuing review.

(6) The IRB has reviewed and approved informed consent procedures and an informed consent document consistent with 50.25. These procedures and the informed consent document are to be used with subjects or their legally authorized representatives in situations where use of such procedures and documents is feasible. The IRB has reviewed and approved procedures and information to be used when providing an opportunity for a family member to object to a subject's participation in the clinical investigation consistent with paragraph (a)(7)(v) of this section.

(7) Additional protections of the rights and welfare of the subjects will be provided, including, at least:

(i) Consultation (including, where appropriate, consultation carried out by the IRB) with representatives of the communities in which the clinical investigation will be conducted and from which the subjects will be drawn;

(ii) Public disclosure to the communities in which the clinical investigation will be conducted and from which the subjects will be drawn, prior to initiation of the clinical investigation, of plans for the investigation and its risks and expected benefits;

(iii) Public disclosure of sufficient information following completion of the clinical investigation to apprise the community and researchers of the study, including the demographic characteristics of the research population, and its results;

(iv) Establishment of an independent data monitoring committee to exercise oversight of the clinical investigation; and

(v) If obtaining informed consent is not feasible and a legally authorized representative is not reasonably available, the investigator has committed, if feasible, to attempting to contact within the therapeutic window the subject's family member who is not a legally authorized representative, and asking whether he or she objects to the subject's participation in the clinical investigation. The investigator will summarize efforts made to contact family members and make this information available to the IRB at the time of continuing review.

(b)      The IRB is responsible for ensuring that:

(i) Procedures are in place to inform, at the earliest feasible opportunity, each participant, or if the participant remains incapacitated, a legally authorized representative of the participant, or if such a representative is not reasonably available, a family member, of the participant’s inclusion in the clinical investigation, the details of the investigation and other information contained in the consent document.
 

(ii) There is a procedure to inform the participant, or if the participant remains incapacitated, a legally authorized representative of the participant, or if such a representative is not reasonably available, a family member, that he or she might discontinue the participant’s participation at any time without penalty or loss of benefits to which the participant is otherwise entitled.
 

(iii) If a legally authorized representative or family member is told about the clinical investigation and the participant’s condition improves, the participant is also to be informed as soon as feasible.
 

(iv) If a participant is entered into a clinical investigation with waived consent and the participant dies before a legally authorized representative or family member can be contacted, information about the clinical investigation is to be provided to the participant’s legally authorized representative or family member, if feasible.
 

(v) If an IRB determines that it cannot approve a clinical investigation because the investigation does not meet the criteria in the exception or because of other relevant ethical concerns, the IRB must document its findings and provide these findings promptly (no longer than within 30 days) in writing to the clinical investigator and to the sponsor of the clinical investigation.

The emergency research will be reviewed by the convened Board. Before approval, the Board will ensure that the above criteria were met. The above will be documented in the minutes indicating that each of the criteria were met before the study was determined to be approvable.

For Planned Emergency Research that is Subject to ICH-GCP (E6) guideline, the additional criteria must be met:

  • The participant or the participant’s legally authorized representative is informed about the clinical trial as soon as possible and provides consent if the participant wishes to continue.

The emergency research will be reviewed by the convened Board. Before approval, the Board will ensure that the additional criterion was met. The above will be documented in the minutes indicating that the additional criteria was met before the study was determined to be approvable.

For Planned Emergency Research that is Subject to DoD Requirements (32 CFR 219) the additional criterion must be met:

  • When conducting emergency medicine research, the Secretary of Defense must approve a waiver of the advance informed consent provision of 10 USC 980.

The emergency research will be reviewed by the convened Board. Where applicable, the compliance associate will ensure documentation of the required waiver is available in the eIRB application prior to IRB approval and it will be documented in the minutes.

Planned emergency research applications require consultation with the Vice Dean for Clinical Investigation prior to IRB review. Legal counsel and OHSR compliance staff will assist the IRB in making the required determinations to comply with FDA and DHHS regulations. Guidance on regulatory requirements will be provided to the research team and IRBs on a case-by-case basis.

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