Exception from Informed Consent (EFIC) for Emergency Research

To Approve an Exception to Acute Care Informed Consent for Planned Emergency Research, the Institutional Review Board (IRB)¹ must find and document FDA 21 Part 50.24, DHHS 45 CFR Part 46.101(i)²:

1. Administration involves life-threatening situations; Available treatment is unproven or unsatisfactory; Collecting evidence is necessary to determine safety and effectiveness
2. Obtaining consent is NOT feasible because:
   1. Subject’s medical condition
   2. Intervention must be administered before it is feasible to consent legally authorized representatives
   3. No reasonable way to identify prospective subjects
3. Research of potential direct benefit to subjects:
   1. Life-threatening situation necessitates intervention
   2. Animal and preclinical studies support the potential direct benefit of the intervention for individuals
   3. Risks are reasonable in relation to
      • What is known about the medical condition
      • Risks and benefits of standard therapy
      • Risks and benefits of proposed intervention
4. Investigation could NOT practicably be carried out without a waiver
5. Investigator has:
   1. Defined length of potential therapeutic window
   2. Is committed to attempting to contact and obtain consent from a legally authorized representative within the window
   3. Will summarize efforts to contact the legally authorized representative at the time of continuing review
   4. Is committed to contacting the subject's family member³ within the window and asking if they object (if obtaining consent from the subject or legally authorized representative is not feasible)
   5. Will summarize efforts to contact family member at the time of IRB continuing review
6. IRB has:
   1. Approved informed consent procedures and documents to be used with the subject/legally authorized representative
   2. Approved procedures and information to be used when providing family members opportunity to object
7. Consultation with representatives of communities from which subjects will be drawn and in which research will be conducted
8. Public disclosure in communities prior to initiation, including:
   1. Plans for study
   2. Risks and benefits
9. Public disclosure to the community at completion of study, including:
   1. Demographics of the population
   2. Results of the study
10. Establishment of an independent data and safety monitoring committee
11. Procedures are in place to inform at the earliest opportunity each subject (if competent), legally authorized representative, and/or family member of:
    1. Subject’s inclusion in study
    2. Details of the study and other information in the informed consent document
    3. Opportunity to discontinue subject’s participation without penalty or loss of benefit to which subject is entitled
12. Additional reporting and recordkeeping, FDA drug and device application requirements must be met [These are outlined in the attached document]

Footnotes

1. IRB review must include concurrence of a licensed physician who is a member or a consultant to the IRB and who is not otherwise participating in the clinical investigation.
2. For Department of Health and Human Services (DHHS) regulated studies, waiver is not applicable to research involving prisoners, fetuses, pregnant women, human in vitro, and fertilization.
3. “Family member” is defined as any one of the following legally competent persons: spouse, parents, children (including adopted children), brothers, sisters, and spouses of brothers and sisters; and any individual related by blood or affinity whose close association with the subject is the equivalent of a family relationship.

Reporting Recordkeeping Requirements: FDA 21 CFR Part 50.24; DHHS 45 CFR Part 46.101(i)

1. For Food and Drug Administration (FDA) regulated investigations, a separate Investigational New Drug application (IND) or Investigational Device Exemption (IDE) is required
   1. Separate IND/IDE identifies protocol as including subjects unable to give consent
   2. Submission of a separate IND/IDE is required even if an IND/IDE for the same drug/device exists
   3. Applications may not be submitted to the FDA as amendments
2. If research is NOT subject to FDA 21 CFR Part 50, but DOES fall in the purview of DHHS 45 CFR Part 46, the IRB must report to the Office for Human Research Protections (OHRP) that an approved acute care informed consent waiver has occurred. [Note: The conditions for approval of DHHS are identical to those outlined in FDA 50.24]
3. If the IRB does NOT approve the waiver request:
   1. IRB must document findings, including reasons for disapproval, and promptly provide to:
      1. Clinical investigator
      2. Sponsor
   2. Sponsor must promptly report disapproval to:
      1. FDA
      2. Other clinical investigators in this or substantially equivalent clinical investigations
      3. Other IRBs reviewing this or substantially equivalent investigations
4. If waiver is approved:
   1. IRB must provide the sponsor with a copy of information that has been publicly disclosed prior to initiation and at completion of the study [Investigator must provide IRB with information]
   2. Sponsors must provide copies to the FDA
5. IRB, Investigator, and Sponsor records must be:
   1. Retained for three years after completion of clinical investigation
   2. Accessible for inspection and copying by the FDA

For detailed information on the FDA’s policies on Exceptions to Informed Consent in Planned Emergency Research, read “Food and Drug Administration (FDA) Guidance for Institutional Review Boards, Clinical Investigators, and Sponsors on Exception from Informed Consent Requirements for Emergency Research”, April 1, 2013