informed consent - exception for emergency research

1. Informed Consent - Exception for Emergency Research Bonnie M. Lee Associate Director for Human Subject Protection Policy Office for Good Clinical Practice Food and Drug Administration

3. Important Note FDA regulations do not allow IRB waiver of the consent requirement or altering of the consent procedure. FDA regulations provide an exception to informed consent for individuals in a life-threatening situation (21 CFR 50.23) emergency research (21 CFR 50.24)

4. Informed Consent - Exception for Emergency Research 21 CFR 50.24, effective 11/1/96 Narrow exception to requirement to obtain and document informed consent For: a limited class of research involving subjects in need of emergency medical intervention, who cannot provide informed consent.

5. Informed Consent - Exception for Emergency Research Based on a Consensus Statement by the Coalition of Acute Resuscitation and Critical Care Researchers (JAMA, April 26, 1995) Needed because �deferred� consent does not equate to informed consent

6. Criteria for IRB Approval Clinical equipoise (Experts question whether the relative benefits and risks of the research intervention are equivalent, or better than, standard therapy) Direct benefit (The intervention must be promising, and must hold out the prospect of direct benefit to the subjects)

7. Criteria for IRB Approval Subjects are in a life-threatening situation requiring intervention Available treatments unproven or unsatisfactory Research is needed to determine safety and effectiveness of intervention under study

8. Criteria for IRB Approval Informed consent is not feasible Subjects cannot consent due to their medical condition and Intervention must start before consent from a LAR is feasible and No reasonable way to identify likely subjects prospectively --21 CFR 50.24(a)(2)

9. Criteria for IRB Approval Study participation holds out prospect of direct benefit to the subjects because: Their life-threatening situation necessitates intervention; Appropriate animal & other preclinical studies have been done & support the potential for direct benefit to the subjects; and Risks are reasonable in relation to the subjects� medical condition; & the risks and benefits of standard therapy and the proposed intervention. --21 CFR 50.24(a)(3)

10. Criteria for IRB Approval The study could not practicably be done without the waiver. Waiver of consent is not appropriate when: Time is sufficient to obtain LAR consent; Most subjects have a LAR readily available Subject population can be identified, and prospective consent obtained, before a predictable, life-threatening emergency; --21 CFR 50.24(a)(4)

11. Criteria for IRB Approval The study plan includes: A defined potential therapeutic window based on scientific evidence; Commitment from the clinical investigator to Try to contact each subject�s LAR within that window to get consent, or a family member who could object to subject�s participation; Summarize these contact efforts and report them back to the IRB at the time of continuing review --21 CFR 50.24(a)(5) & (7)(v)

12. Criteria for IRB Approval There must be: Informed consent procedures, and An informed consent document to be used where feasible for subjects or legally authorized representatives, and Information to be used when providing an opportunity for a family member to object to the subject�s participation in the study. --21 CFR 50.24(a)(6)

13. Criteria for IRB Approval There must be procedures: To inform, asap, each subject, LAR, or family member, as appropriate The details of the study after the subject�s inclusion in the study Right to discontinue participation in the study without penalty or loss of benefits Must be disclosed in event of subject�s death --21 CFR 50.24(b)

14. Special Protections Independent data monitoring committee to exercise oversight of the investigation. ************** Community consultation Public Disclosure to the communities before and after the study --21 CFR 50.24(a)(7)(i), (ii), & (iv)

15. Requests to Use the Rule In 6+ years since it was effective: Approx. 30 requests to use the rule Approx. 20 protocols allowed to proceed under the rule

16. Common issues/deficiencies Study not appropriate for 50.24 exception No informed consent document or procedures No procedures for informing LAR or family member that subject was enrolled in study (in the event of the subject�s death) Minimal or no plans for community consultation Minimal or no plans for public disclosure

17. Common issues/deficiencies Failure to define the therapeutic window �Independent� Data Monitoring Committee

18. Initial Community Consultation Who? Community where research will take place Community from which subjects will be drawn When? Prior to initiation of the study Why? Allows the community(ies) to discuss the research with the investigators, and to provide feedback to the IRB

19. Public Disclosure Who? Same communities (plus research community) When and What? Before initiation of the study Study plans (not usually disclosed by sponsor) Informed consent won�t be obtained from most subjects subjects After study is completed Comprehensive summary data sufficient to apprise the communities and researchers of the study results Demographic information about the research population

20. Consultation & Disclosure How much is enough? One town meeting? A legal notice in the local paper? Informing hospital staff? An ad with a phone number for the public to call for more information?

21. Consultation Rule doesn�t dictate how or what to do Communities differ [N.Y.City v. village] size, homogeneity of population, languages... Effective consultation Multifaceted Informative to IRBs and communities Continuing

22. Consultation Need to determine the demographics of the potential subject population review demographics of patients previously treated for the condition under study Need to determine the demographics of the community in which the research will be conducted geographic region, e.g., city or region

23. Consultation Go to �Gatekeepers� to groups to develop plan for consultation Elicit interest: newspaper articles, talk shows, advertise meetings Address skepticism/special concerns Use existing (better attendance) v. special (folks with strong interest) meetings

24. Consultation - 2-way Communication Inform community no informed consent for most subjects risks and potential benefits right to refuse and how to be excluded Community informs IRB support for, or concerns about, the research activity Exchange of Information

25. Consultation IRB must hear/learn of concerns IRB may approve study or change study (e.g., limit enrollment) or decide it is inappropriate decide more consultation is needed

26. Consultation Provides �sunshine� to the research enterprise It IS NOT intended to substitute for consent (i.e., the community does not vote yea or nay)

27. What can you do? National EMS Research Agenda calls for: evaluating current regulatory requirements identifying those that are impediments to EMS research then, develop EMS-specific consent strategies appropriate revisions to existing regulations

28. What can you do? Model: The Coalition of Acute Resuscitation and Critical Care Researchers evaluate current regulatory requirements identify impediments to EMS research develop EMS-specific consent strategies appropriate revisions to existing regulations Reach a consensus

29. What can you do re consultation? If community consultation and community disclosure requirements are a particular concern: develop a model for how such requirements ought to be fulfilled a model establishes a voluntary standard avoids �recreating the wheel� at each site

30. What can you do re consultation? Use existing networks to enlist the public civic: e.g. schools, churches, social clubs occupational: e.g., businesses, professional organizations informational: e.g., media, internet, libraries Incorporate public health messages how to lower risk of condition/disease

31. What can you do re consultation? Nurture trust and confidence candor openness to media effective communication Consider a citizen advisory panel to plan outreach

32. What is FDA doing? Developing guidance re informed consent in large scale public health emergencies when informed consent is required how to facilitate information dissemination, comprehension, voluntariness, and consent when informed consent is not required how the existing exceptions may be applied in this situation

33. Our Goal Protect research subjects Improve EMS, patients� survival and outcomes Not, to necessarily make doing the research �easy�