1. Accreditation of Research Programs: How it Might Affect your Research Harvey Murff, M.D., M.P.H. Director of Research Safety GCRC, Vanderbilt University Medical Center

2. Accreditation of Research Programs: How it Might Affect your Research The problem that accreditation would address The problem that accreditation would address What is accreditation What is accreditation Why is it believed that accreditation might help Why is it believed that accreditation might help Who will accreditation affect Who will accreditation affect

3. Accreditation of Research Programs: How it Might Affect your Research The problem that accreditation would address The problem that accreditation would address What is accreditation What is accreditation Why is it believed that accreditation might help Why is it believed that accreditation might help Who will accreditation affect Who will accreditation affect

4. Human Subjects Protection -Background Nuremberg Code (1946-1949) Nuremberg Code (1946-1949) Declaration of Helsinki by World Medical Association (1963) Declaration of Helsinki by World Medical Association (1963) National Research Act (1974) National Research Act (1974) –Formed National Commission for the Protection of Human Subjects of Biomedical and Behavioral Research (National Commission) The Belmont Report (1979) The Belmont Report (1979)

5. Human Subjects Protection -Background National Commission described what would be the framework for IRB’s National Commission described what would be the framework for IRB’s –Not adopted by all Federal Agencies The “Common Rule” published (1991) The “Common Rule” published (1991) Office of Inspector General (OIG) issues Intuitional Review Boards: A Time for Reform (1998) Office of Inspector General (OIG) issues Intuitional Review Boards: A Time for Reform (1998) –IRB’s facing overwhelming demands

6. Human Subjects Protection -Failures in the System OPRR halts research at Duke (May 1999) OPRR halts research at Duke (May 1999) –Several other sites temporarily shut down –Noncompliant with human protection regulations Death of Jesse Gelsinger (September 1999) Death of Jesse Gelsinger (September 1999) –Cited for no safety plan in proposal OIG issues follow up to A Time for Reform OIG issues follow up to A Time for Reform –Again calls into question the effectiveness of IRB’s –Suggest greater attention to protecting human subject in any trial (not just gene therapy)

7. Human Subjects Protection -Regulatory Guidelines Secretary of Health and Human Services (2000) Secretary of Health and Human Services (2000) –commissions IOM to review human subjects protection Two reports Two reports –“Preserving Public Trust: Accreditation and Human Research Participant Protection Programs” (2001) –“Responsible Research: A Systems Approach to Protecting Research Participants” (2002)

8. Purpose of the IOM Committee 1. Comprehensive assessment of research participant protection 2. Review and consider proposed human research review program performance standards 3. Recommend standards for accreditation of HRPPPs, considering measures of structure, process, and performance, as well as resource sufficiency 4. Recommend steps that the organizations and institutions than conduct research and that the federal government should take to collect and analyze data to monitor and evaluate how well the system for protecting human subjects is operating

9. The Phases of Human Research Research Question Protocol Development Scientific and Conflict of Interest Review Ethical Review Recruitment and Enrollment Data Collection Data Analysis/Study Close-Out Dissemination Individual Participant Participant Perspective Informed ConsentSafety Monitoring

10. Statement of Problem Significant doubt exist regarding the capacity of the current system to meet its core objectives Significant doubt exist regarding the capacity of the current system to meet its core objectives IRBs are “under strain” and “in need of reform” IRBs are “under strain” and “in need of reform” The existing regulatory framework cannot adequate respond to the complex and ever- changing research environment, with weaknesses related to gaps in authority, structure, and resources The existing regulatory framework cannot adequate respond to the complex and ever- changing research environment, with weaknesses related to gaps in authority, structure, and resources

11. Human Research Participant Protection Program Performance Assessment Monitoring and Feedback EducationQuality Improvement Participants Research Organizations IRBsInvestigators Research Involving Human Participants Sponsors

12. Functions of a HRPPP Comprehensive review of protocols Comprehensive review of protocols –Scientific –Financial conflict of interests –Ethical reviews Ethically sound participant-investigator interaction Ethically sound participant-investigator interaction Ongoing and risk-appropriate safety monitoring Ongoing and risk-appropriate safety monitoring Quality improvement and compliance activities Quality improvement and compliance activities –What are the types of quality problems?

13. Common Quality Problems Most common findings in quality assessment of clinical trials Most common findings in quality assessment of clinical trials –Case report forms and study files incomplete, inaccurate, and not appropriate for safety tracking –Failure to distinguish research from standard of care –Failure to submit or amend IND/IDE to FDA –Poorly written protocols and data collection tools –Informed consent form inadequacies/inconsistencies –No study coordinator with defined authority –Post-approval monitoring for data integrity inadequate Source- Sherwin, Research Practitioner, 2002

14. Accreditation of Research Programs: How it Might Affect your Research The problem that accreditation would address The problem that accreditation would address What is accreditation What is accreditation Why is it believed that accreditation might help Why is it believed that accreditation might help Who will accreditation affect Who will accreditation affect

15. What is Accreditation? A process based on self- and peer assessment for public accountability and improvement of performance quality. Peers assess the quality of an institution or academic program and assist the faculty and staff in improvement. A process based on self- and peer assessment for public accountability and improvement of performance quality. Peers assess the quality of an institution or academic program and assist the faculty and staff in improvement. –self-study using the accrediting organization’s set of expectations about quality (standards, criteria) as their guide. “ –A team of peers, selected by the accrediting organization, reviews the evidence, visits the campus to interview the faculty and staff, and writes a report of its assessment including recommendation to the commission of the accrediting organization (group of peer faculty and staff, professionals, and public members). Grounded by a set of expectations about quality and integrity, the commission reviews the evidence and recommendation, makes a judgment, and communicates the decision to the institution and other constituencies if appropriate. Grounded by a set of expectations about quality and integrity, the commission reviews the evidence and recommendation, makes a judgment, and communicates the decision to the institution and other constituencies if appropriate.

16. Why Accreditation Accreditation versus regulation Accreditation versus regulation –Benefits »Reduces cost of government oversight »More flexible and responsive to change that federal agencies »More responsive to the “regulated” –Disadvantages »Less accountable “fox is guarding the henhouse” “fox is guarding the henhouse”

17. Proposed Accreditation Agencies –National Committee on Quality Assurance (NCQA) »Contracted by the VA »Undergoing pilot testing »Centers poorly prepared –Association for the Accreditation of Human Research Protection Programs, Inc (AAHRPP) »Few institutions already on board

18. Who is advocating accreditation? –Institute of Medicine –Department of Veterans Affairs –National Bioethics Advisory Commission –Inspector General of the Department of Health and Human Services –American Association of Medical Colleges –Members of Congress –Office of Human Research Protection (OHRP)

19. Accreditation of Research Programs: How it Might Affect your Research The problem that accreditation would address The problem that accreditation would address What is accreditation What is accreditation Why is it believed that accreditation might help Why is it believed that accreditation might help Who will accreditation affect Who will accreditation affect

20. How accreditation should improve quality and safety Grounded in continuous quality improvement theories Grounded in continuous quality improvement theories Requires measuring of processes and outcomes, introducing changes, and re- measuring Requires measuring of processes and outcomes, introducing changes, and re- measuring –Statistical process control

21. “If you always do what you always did, you will always get what you always got”

22. Definitions: Quality Quality –IOM definition: »“degree to which health services for individuals and populations increase the likelihood of desired health outcomes and are consistent with current professional knowledge” Quality Assurance Quality Assurance »“The policy, procedures, and systematic actions established in an enterprise for the purpose of providing and maintaining a specified degree of confidence in data integrity and accuracy throughout the lifecycle of the data, which includes input, update, manipulation, and output.”

23. Model of Continuous Quality Improvement PlanAct StudyDo

24. Barriers to a Quality Assurance Approach What’s the evidence? What’s the evidence? What outcomes? What outcomes? What methods? What methods? What resources? What resources? Local buy-in Local buy-in

25. Accreditation of Research Programs: How it Might Affect your Research The problem that accreditation would address The problem that accreditation would address What is accreditation What is accreditation Why is it believed that accreditation might help Why is it believed that accreditation might help Who will accreditation affect Who will accreditation affect

26. Who will be evaluated in accreditation programs? Institutions Institutional Review Boards Investigators

27. Investigators VA’s GCP Checklist VA’s GCP Checklist –Paperwork to be completed documenting compliance with protocol Investigator performance measures Investigator performance measures –Using only trained individuals to gather consent –Documentation of consent –AE reporting Investigator Responsibilities for Reporting to IRB –Reporting of unanticipated problems –Submission of protocol changes –Reporting of protocol deviations Obtaining informed consent –When and where –Opportunity to consider to participate –Comprehension

28. General Recommendations of IOM 1. Protect Every Research Participant 2. Refocus the mission of the IRB on the thorough ethical review and oversight of research protocols 3. Recognize research participants’ contribution and integrate them into the system 4. Maintain high standards for the continuing review of HRPPP performance

29. Protect Every Research Participant Establish accountability within an ethical research culture Establish accountability within an ethical research culture –Accountability –Adequate resources –Ethics education programs –Transparency Provide sufficient funds Provide sufficient funds

30. Refocus IRB mission on ethical review of protocols Distinguish scientific, conflict of interest, and ethics review mechanisms Distinguish scientific, conflict of interest, and ethics review mechanisms Emphasize risk-appropriate protection Emphasize risk-appropriate protection Increase program productivity Increase program productivity

31. Recognize and Integrate Participant Contributions Revitalize informed consent Revitalize informed consent Increase system accessibility Increase system accessibility Compensate participants for research- related injury Compensate participants for research- related injury

32. Maintain Vigilance Collect national level data about the system Collect national level data about the system Enhance safety monitoring Enhance safety monitoring Continuously improve quality Continuously improve quality Manage potential conflicts of interest Manage potential conflicts of interest Periodically assess the national system Periodically assess the national system