Conducting Research during Public Health Emergencies

1. Conducting Research during Public Health Emergencies RADM Ali S. Khan, MD, MPH October 30, 2007 SACHRP Panel on Disaster Research

2. CDC’s Mission … "to promote health and quality of life by preventing and controlling disease, injury, and disability." Strategic imperative: Public Health Research: Create and disseminate the knowledge and innovations people need to protect their health now and in the future.

3. Public Health Emergencies • Outbreaks • Natural disasters • Biological, chemical or nuclear terrorism • Other public health threats

4. Defining non-research activities in the context of emergency response • CDC’s 1999 guidance document • Most activities during emergency responses tend to be non-research • Purpose is not to contribute to generalizable knowledge • Purpose is to gain the information needed to solve an immediate threat

5. Non-research • Hurricane Katrina • Environmental assessments • Surveillance • SARS • Case finding • Virus characterization • Assay development

6. Research determination To prevent mis-labeling of research as non-research… • Determination is the responsibility of each National Center • Not investigator driven • Associate Director for Science and the Human Subjects Contact • Research protocols are submitted for IRB review • Emergency IRB review option

7. Why conduct research during emergencies? • Sometimes research is an appropriate response tool • Other times, emergencies present a unique opportunity to gain knowledge • Public health imperative • Be mindful that research is a privilege! • There is a fine line between opportunity and exploitation.

8. Defining research in the context of emergency response • Response activities that could be considered research • Additional analyses beyond those needed to solve the immediate health problem • Investigation of a non-standard intervention or comparison of standard interventions • Storage of specimens for future use in research • Long-term epidemiologic follow-up

9. Research as a response tool: Rift Valley Fever • Suspect Ribavirin may be effective treatment based on animal models • Efficacy had not been demonstrated • Placebo-controlled trial proved Ribavirin was not effective treatment and uncovered side effects

10. Public Health Imperative World Trade center • 1993 – Case control study to determine risk factors for smoke-related morbidity • Identified factors related to evacuation and safety systems • Recommendations from this study led to significant improvements, saving lives in the 2001 attack • 2001 – Biomonitoring study of firefighters to determine contaminant exposures • Included comparison group of unexposed firefighters

11. Unique opportunities: Ebola & SARS • Ebola • Phage display libraries • Human monocolonal antibodies • SARS • Follow up of pregnant mothers and their infants • Continued development of laboratory assays • Follow up studies of persistence of anti-SARS antibodies

12. Challenges to getting emergency research approved • Delays of convening an IRB during an emergency and timeliness of review • Timeliness of multiple IRB review • Requirement for Federal-wide assurances

13. Missed opportunities: Monkeypox and SARS • Natural History Study – Monkey Pox • Transmission dynamics and risk among specific populations

14. Potential solutions: Obtaining IRB review • Standing or “just in case” protocols • Lacks flexibility • Cannot anticipate all possible emergencies • IRBs are hesitant to approve • Can be burdensome to maintain • Emergency IRB review • Can be difficult to attain quorum on short notice

15. “Just-in-Case” • SARS: following the SARS outbreak, investigators developed a protocol to cover all of the things they would like to study the next time SARS came around… • Prepared all data collection instruments in advance • Prepared consent forms • Obtained IRB approval • Shared with State health departments

16. Possible solutions:multiple sites • Simultaneous IRB review • Differing interpretation of regulatory requirements • Centralized IRB review • Requires IRB Authorization Agreement and amending FWA • Does not adequately consider local context

17. Possible Solutions: FWAs • Unaffiliated investigator agreement • Applicability is limited • Can be burdensome if needed for a large number of investigators

18. Possible regulatory solutions • Designate exemption category for research during emergencies under 46.101(b) • Waive applicability of regs for emergency research as a class under the provision for Secretarial waiver, 45 CFR 46.101(i) No IRB review ≠ No ethical consideration! Currently at CDC: Exemptions under 101(b) are made at the Agency level, and are reviewed by both the Center ADS and the Human Research Protection Manager

19. Possible regulatory solutions • Allow expedited review of greater than minimal risk research during emergencies (to be followed by convened review as soon as is feasible)

20. Possible regulatory solutions: multiple sites • Pre-designation of CDC IRB as central IRB for public health emergencies • Allow for informal IRB reliance relationships during emergencies • Without IRB Authorization Agreement • Without amending FWA • Suspend FWA requirement • Allow local sites to engage in HHS-conducted research without FWA during emergencies

21. Additional considerations • Coordination with local health departments • Local context • Integration of local investigators • Prevent duplication of activities • Anticipation and planning • Prepare protocols in advance • Community pre-consent • Standing pre-event committees

22. Laura Youngblood Lauren Stockman Drue Barrett Tom Sinks Susan Stokes Rita Helfand Inger Damon Robin Ikeda Mike McGeehin Dan Sosin Mike Gerber Lisa Lee Dixie Snider Acknowledgements