1. EXCEPTION FROM INFORMED CONSENT IN CPR DEVICE TRIALS: PROTECTION OF PATIENTS’ RIGHTS Circulatory System Devices Panel Meeting September 21, 2004 Elisa D. Harvey, D.V.M., Ph.D. Acting Director, IDE Program FDA Office of Device Evaluation

2. 2 BACKGROUND Informed consent is a fundamental element of human subject research protection in clinical research –Declaration of Helsinki –Belmont Report Consent by legally authorized representative (“proxy”) long accepted for research populations incapable of providing informed consent (e.g., pediatric population, cognitively impaired) Prior to 1996, NO provision in regulations for ANY exception from informed consent requirement (individual or by proxy)

3. 3 EMERGENCY SITUATIONS Medical intervention may be urgently needed in situations where individual is unconscious or otherwise unable to provide consent; HOWEVER, –Urgency of situation may preclude obtaining consent by proxy –This kind of research is urgently needed

4. 4 1996: NEW FDA REGULATION Addressed need to permit exception from informed consent requirement in specific situations Recognized need for additional protection of patients’ rights when research undertaken with consent waived Regulation developed with substantial input from medical community –Open meetings –Comment on draft regulation published 1995

5. 5 21 CFR 50.24 Identifies criteria for studies that may be conducted with exception from informed consent Establishes requirements for study conduct Specifies additional steps sponsors must take to assure patient protection

6. 6 CRITERIA FOR CONDUCTING STUDIES WITH EXCEPTION FROM INFORMED CONSENT Subjects are in life-threatening situation Available treatments are unproven and/or unsatisfactory Participation in study holds prospect of direct benefit to patients Study could not feasibly be conducted without exception from informed consent requirement

7. 7 FEASIBILITY Too few patients who would be able to provide consent, or who would have acceptable proxy available to provide consent within reasonable time interval Not possible to prospectively identify population from which study patients would likely be drawn

8. 8 STUDY CONDUCT Investigators must make every attempt to obtain consent from legally authorized representative within specified time interval before proceeding to enter patient in study Investigators must inform patient and/or representative about study as soon as possible

9. 9 ADDITIONAL PROTECTIONS Separate IDE must be submitted to and approved by FDA for such studies IRB(s) must consult with communities where study would be conducted Study must be publicly disclosed to these communities prior to initiation, and results publicly disclosed when study completed Study must be overseen by an independent data safety monitoring board (DSMB) IRBs for study sites must be notified of concerns raised by IRBs of other participating sites

10. 10 FDA GUIDANCE DOCUMENT Draft guidance issued in 2000 http://www.fda.gov/ora/compliance_ref/bimo/err_guide.htm Attempts to clarify requirements Informed by initial experiences conducted under 21 CFR 50.24 Public comments on draft identified need for further clarifications Revisions to guidance are underway

11. 11 EXPERIENCE Studies have been conducted since 1996 with exception to informed consent requirement –Public Access Defibrillation (PAD) Trial (2004 NEJM 351[7]: 637-646) Some investigators have described their approaches to the regulatory requirements in detail Such reports helpful in developing more informed consensus regarding optimal approaches for these studies

12. 12 CURRENT STATUS Draft guidance being revised to incorporate public comments, provide clarification on some points Past experience should facilitate increased efficiency in future investigations done under this regulation Sponsors, investigators, IRBs and FDA reviewers are all still in learning mode with regard to “best practices”

13. 13 Questions? elisa.harvey@fda.hhs.gov OR edh@cdrh.fda.gov 301-594-1190 x 154