Exception from Informed Consent in Emergency Research

1. Exception from Informed Consent in Emergency Research • Designed for implementation of research in emergency settings when exception from informed consent is requested under 21 CFR 50.24 http://www.fda.gov/ora/compliance_ref/bimo/err_guide.htm

2. Criteria • The exception applies when: • Human subjects cannot give informed consent because of emerging, life-threatening medical condition • Available treatments for the condition are unproven or unsatisfactory • The intervention must be administered before informed consent from LAR is feasible

3. Benefits and Risks • Participation must hold out prospect of direct benefit to the subject • If placebo design is used, standard care must be given to all subjects • Risks of the study are reasonable in relation to: • What is known about the medical condition of the potential subjects • The risks and benefits of standard therapy • Any benefits of the proposed treatment

4. Study Design • Design should be adequate to the task of evaluating whether the treatment provides the hypothesized effect • The therapeutic window must be defined • The amount of time spent in locating family members must be defined

5. Contact of Family Members • Attempts to contact a legally authorized representative (LAR) or family member need not exhaust the entire therapeutic window • The effect of delaying study treatment must be taken into account when determining the portion of the therapeutic window to be spent trying to locate family

6. Public Disclosure and Community Consultation • Prior to start of the study -- public disclosure of sufficient information to describe : • the nature and purpose of the study • the fact that informed consent will not be obtained for most study subjects • Following completion of the study information about the study results must be disclosed • to the community where the research was done • the research community should have access to comprehensive summary data

7. IRB Responsibilities Specific to Waiver of Consent • Review/approve proposed plan and procedures for contacting LAR/family • Review/approve community notification and consultation plan • Attend/participate in community consultation activities

8. Community Notification and Consultation Plan • Each center must submit a written plan for: • Notification: activities to inform the community about the trial and use of waiver of consent • Consultation: activities that permit community members to express their views and offer opinions, suggestions, and feedback about the trial and use of waiver of consent

9. Community Consultation • Shared obligation of the clinical investigator, IRB, and sponsor • Content should include discussions of: • The fact that informed consent will not be obtained for most study subjects • The risks and potential benefits for the subjects • Ways that individuals or groups can indicate desire to be excluded

10. Notification Strategies • Purpose: to provide information • Options: • Public service announcements • Print media • Television and radio • Web site • 800 number with recorded message • Other?

11. Consultation Strategies • Hospital and non-hospital based groups • Presentation/discussion/feedback • Hospital’s community outreach programs • Religious organizations • Academic groups • Civic groups • Patient advocacy groups • “Talk radio” shows • Television shows with call-in feature

12. Consultation Plan Elements • Description of the community • Strategies for notification • Strategies for consultation • Documentation procedures for activities, feedback and responses

13. Community Description • Description of the community: • Major ethnic, racial, cultural groups • Significant health care issues • Major social influences • Other factors? • Resources • US Census website • Hospital admission/service statistics • Newpapers/media

14. Reasons for Exclusion in NABIS:H I

15. Currently Available Cooling Technologies • Surface Cooling Devices • Standard cooling pads • Rapr-Round Cooling Suit by Gaymar Inc. • Arctic Sun Temperature Pads by Medivance Inc. • Intravascular Cooling Devices • Cool Line and Icy Catheters by Alsius Corp. • Celsius Control System by Innercool Therapies • Reprieve Set Point Endovascular System by Radiant Medical

16. Poor body surface area contact Placement of sheets or other materials between patient’s skin and blanket Stiff and inflexible Obscure patient’s body for observation and access for care Standard Cooling Pads

17. Designed to: Provide maximal surface contact Stay put with turning or moving the patient Permit access and visualization of the patient The Rapr-Round -- Gaymar

18. Arctic Sun -- Medivance http://www.medivance.com

19. Cool Line and Icy -- Alsius The Cool Line – smaller, 2 balloons Icy – larger, 3 balloons

20. Celsius Control System – Innercool

21. Reprieve Endovascular System – Radiant Inc

22. Balance-beam Performance

23. Posture Reflex Scores *p<0.5

24. NABIS:H I Admission Temp and Outcome

25. NABIS:H IOutcome in Patients with Admission Temp < 35 C and Age < 45

26. NABIS:H IEffect of Admission Temp on Outcome

27. The FDA requires a separate IDE for devices that are used in trials using waiver of consent.