1. Who Ultimately Protects Human Research Subjects? Presented by Bernard A Schwetz, D.V.M., Ph.D. Director Director Office for Human Research Protections Town Meeting Columbia University Medical Center October 12, 2004

2. Topics The research enterprise The research enterprise Does compliance protect subjects? Does compliance protect subjects? Adjuncts to compliance Adjuncts to compliance Compliance based on trust Compliance based on trust How do we prevent the next tragedy? How do we prevent the next tragedy? Threats to the enterprise Threats to the enterprise

3. SPONSORS Industry, Government agencies, others Human Research Enterprise RESEARCH INSTITUTIONS IRB’s committees: protocol, COI, radiation, biosafety, etc. PAYERS,INSURERS DSMBREGULATORYOVERSIGHT FDA, Common Rule Agencies state and local government STUDY SUBJECTS RECIPIENTS the public – productsproducts knowledgeknowledge ACCREDITINGORGANIZATIONSAAHRPPPHRP EDUCATORS CRO Patient Representatives Advocacy Groups RESEARCH TEAMS InvestigatorsCollaborators Team members SMO

4. Does Compliance Protect Subjects? Yes, But… How much? How much? From what? From what?

5. Adjuncts to Compliance Common sense Common sense Institutional attitude Institutional attitude Adequate resources Adequate resources Accreditation of HRPPs Accreditation of HRPPs Certification of investigators, IRB members Certification of investigators, IRB members

6. Compliance Based on Trust Compliance Models a.On-site inspectors, full time b.Self audit, government inspected c.Trust (HSP programs) Guidance versus flexibility

7. Who is Responsible for Protection? IRB IRB Sponsor Investigator FDA or OHRP Subject Subject Where is compliance critical?

8. How Can We Prevent The Next Tragedy? Background around a threshold Background around a threshold Tragedies Tragedies - Un anticipated, accidents - Preventable Risks to subjects

9. Sources of Risks Inadequate training Inadequate training Conflicting, completing interests Conflicting, completing interests Non-compliance Non-compliance Inadequate or poorly used HRPP resources Inadequate or poorly used HRPP resources Error in judgment, flawed procedure Error in judgment, flawed procedure Clinical vs. research decisions Clinical vs. research decisions Non-credentialed professionals, institutions Non-credentialed professionals, institutions Institutional indifference Institutional indifference Gaps in regulations Gaps in regulations

10. How Can We Anticipate The Next Tragedy? Failure analysis models Failure analysis models Near-miss evaluations Near-miss evaluations

11. Potential Consequences of the Next Tragedy Mandatory certification of investigators Mandatory certification of investigators Mandatory accreditation of HRPPs Mandatory accreditation of HRPPs Regulations apply to all research Regulations apply to all research Injury to subjects covered by sponsor Injury to subjects covered by sponsor Single federal office for HSP Single federal office for HSP

12. Threats to the Enterprise Burdens to the enterprise Burdens to the enterprise People unwilling to be research subjects People unwilling to be research subjects –Fear of harm –Distrust of researchers –Cost –Inconvenience –Others

13. Burdens on the Enterprise 1. Burdens created by regulations 2. Burdens of non-regulatory origin - Doing what’s right - Over-interpretation of regulations - Treating guidances as regulations - Fear of litigation 3. Gaps in the regulations/guidance's

14. Does Compliance Protect Subjects? Yes, but not completely. Minimum standard May not prevent another tragedy

15. Final Thoughts Protection of human subjects is primary concern Protection of human subjects is primary concern Compliance by itself is not enough Compliance by itself is not enough Success of the research enterprise depends on public trust Success of the research enterprise depends on public trust