Conducting Research during Public Health

Emergencies

RADM Ali S. Khan, MD, MPH

October 30, 2007

SACHRP Panel on Disaster Research

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.

Public Health Emergencies

Outbreaks Natural disasters Biological, chemical or nuclear terrorism Other public health threats

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

Non-research

Hurricane Katrina Environmental

assessments Surveillance

SARS Case finding Virus characterization Assay development

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

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.

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

Defining research in the context of emergency response

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

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

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

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

Missed opportunities: Monkeypox and SARS

Natural History Study – Monkey Pox

Transmission dynamics and risk among specific populations

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

“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

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

Possible Solutions: FWAs

Unaffiliated investigator agreement Applicability is limited Can be burdensome if needed for a large

number of investigators

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

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)

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

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

Acknowledgements

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