EXCEPTION FROM INFORMED CONSENT IN CPR DEVICE TRIALS: PROTECTION OF PATIENTS’ RIGHTS

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