Copyright © 2009 AAHRPP ® All rights reserved Update on AAHRPP – Revised Standards and Procedures Marjorie A. Speers, Ph.D. President and CEO

AAHRPP  Non-profit organization founded in 2001 –Association of American Medical Colleges –Association of American Universities –Association of Public and Land-grant Universities –Consortium of Social Science Associations –Federation of American Societies for Experimental Biology –National Health Council –Public Responsibility in Medicine and Research  Sole accrediting body in the United States  Offer accreditation worldwide

What is Accreditation of a Human Research Protection Program?  Accreditation of an Organization: –is voluntary –is flexible –is based on outcome-based standards consistent regulatory, legal, and ethical requirements allows a proportionate risk management approach –evaluates structures, processes, and outcomes –is not an audit of ethics decisions –is not an audit of individual studies –focuses on quality

How Does Accreditation Work? Council on Accreditation Determines accreditation category On-site evaluation Tailored to setting Expert Site Visitors Self-assessment Self-study that leads to application

The Accreditation Process – Step 1/2 Self Assessment Submit Application Draft Site Visit Report Accreditation Determination Council on Accreditation Response Evaluation Prepare Response Evaluation of Written Materials Submit Revised and Additional Materials Site Visit – Evaluation of Practices Element by Element Feedback Feedback as Needed

Council on Accreditation Determinations  New applicants –Full accreditation –Qualified accreditation –Pending –Withheld  Renewing applicants –Full accreditation –Pending –Probation –Revoked

Accredited Organizations  As of September 2009, 194 organizations representing more than 930 entities: –Contract research organizations, hospitals, independent IRBs, research institutes, universities and government agencies –Small (fewer than 20 protocols) and large (greater than 6,000 protocols) institutions –Clinical and non-clinical research programs –International programs: Canada, Singapore, and South Korea

Who’s Accredited  95% VA facilities that conduct research involving humans  42% American medical schools  38% teaching hospitals  45% research-intensive universities  36% central IRBs  Pfizer phase 1 clinical research units

Standards Development  First Set of Standards (Current Standards) –May 2001 – AAMC working group PRIMR standards NCQA standards for VA program IOM Report – Preserving Public Trust –October 1 – Board of Directors and CEO Interim standards –Public Comment Period –February Released Standards and Launched Program  Board of Directors adopted a procedure to review the accreditation standards approximately every 10 years

Current Standards  Five Domains Organization IRB Investigator Sponsored Research Participant Outreach  22 Standards  77 Elements

Experience with Current Standards  Some minor revisions made in 2004  Comprehensive  Initially, organizations were not prepared to meet the accreditation standards Accreditation was a new concept and process Federal regulatory requirements Additional requirements  AAHRPP’s emphasis was on written documents rather than practice

Major accreditation findings  Of the 77 elements, 21 pose challenges –Domain I –Domain II –Domains III - V

Accreditation Findings – Domain I  Definition of research involving human subjects –Missing FDA definitions –Definitions inconsistent with federal regulations  Criteria for exemptions –Do not take into account FDA regulations –Do not take into account OHRP guidance  Definitions of legally authorized representative, child, guardian –Which individuals within your state meet the federal definitions

Accreditation Findings – Domain I  Investigator conflict of interest –Missing FDA and PHS disclosures –Missing a procedure that the IRB has the final authority to decide whether the research is approvable  Non-compliance –Definitions, determinations, actions, reporting  Unanticipated problems involving risks to participants or others (I.3.J) –Process to determine whether a problem is an “unanticipated problem involving risks to participants or others” –Reporting  INDs and IDEs –Missing process to determine whether IND or IDE is required –Missing process to verify that the IND or IDE is correct

Accreditation Findings – Domain II  IRB composition and evaluation –Missing an evaluation process for the IRB chair and members –Missing a requirement to include someone on the IRB who represents the views of participants  Procedures for review using the expedited procedure Missing applicability criteria Missing definition of “minor”  Continuing review Missing a status report or status report is incomplete  Missing documentation of required determinations

Accreditation Findings – Domain II  Evaluation of risks and potential benefits –Missing the three regulatory criteria  Evaluation of data and safety monitoring plan –Missing an evaluation component  Suspension and termination of IRB approval –Definitions of suspension and termination –Consider consequences of suspension or termination for enrolled participants –Reporting

Accreditation Findings – Domain II  Protection of privacy interests –Understanding the difference between privacy and confidentiality –Missing as a criterion for approval of research  Consent process –Missing evaluation of the consent process –Missing required disclosure elements –Missing FDA requirements pertaining to consent –Confusion between waiver of the consent process and waiver of documentation of the consent process –Confusion of requirements for implementing the exception to obtain consent in emergency situations

High-Quality Human Research Protection Programs  Distinctions –Strong integrated plan for human research protection –Strong program for scientific review –Strong and highly motivated organizational leader –Program for review of resources for the HRPP –Research specific IRBs –Strong network of communication among units –Policy and procedure to identify and manage organizational conflict of interest –Strong quality improvement programs –Strong education programs for researchers and staff –Highly competent IRB chairs, members, or staff –Impressive educational materials for the community

Standards Review Process  2008 –Standards Revision Committee formed and reviewed the standards, made recommendations  2009 –Council on Accreditation reviewed the recommendations –Board of Directors reviewed the recommendations and approved the proposed revised accreditation standards for public comment –Public comment period – 60 days

Standards Review Process  Staff, Council on Accreditation, and Board of Directors reviewed the comments and recommendations  Board of Directors approved the Final Revised Accreditation Standards  Final Revised Accreditation Standards published on October 1 –Effective March 1 –Organizations may apply under the Final Revised Accreditation Standards now  Evaluation Instrument for Accreditation for use with the Final Revised Accreditation Standards also published

What’s New in the Revised Standards  Organization of the Standards –Grouped into three Domains More logical framework for a human research protection program Better definition of the primary roles and responsibilities of the entities that comprise a human research protection program

Three Domains  Human Research Protection Program Domain 1: Organization Domain 2: IRB or Ethics Committee Domain 3: Researcher and Research Staff

Domain I: Organization  Standard I-1: The Organization has a systematic and comprehensive Human Research Protection Program that affords protections for all research participants. Individuals within the Organization are knowledgeable about and follow the policies and procedures of the Human Research Protection Program.  Standard I-2: The Organization ensures that the Human Research Protection Program has resources sufficient to protect the rights and welfare of research participants for the research activities that the Organization conducts or oversees.  Standard I-3: The Organization’s transnational research activities are consistent with the ethical principles set forth in its Human Research Protection Program and meet equivalent levels of participant protection as research conducted in the Organization’s principal location while complying with local laws and taking into account cultural context.

Domain I: Organization  Standard I-4: The Organization responds to the concerns of research participants.  Standard I-5: The Organization measures and improves, when necessary, compliance with organizational policies and procedures and applicable laws, regulations, codes, and guidance. The Organization also measures and improves, when necessary, the quality, effectiveness, and efficiency of the Human Research Protection Program.  Standard I-6: The Organization has and follows written policies and procedures to ensure that research is conducted so that financial conflicts of interest are identified, managed, and minimized or eliminated.  Standard I-7: The Organization has and follows written policies and procedures to ensure that the use of any investigational or unlicensed test article complies with all applicable legal and regulatory requirements.  Standard I-8: The Organization works with public, industry, and private Sponsors to apply the requirements of the Human Research Protection Program to all participants.

Domain II: IRB or EC  Standard II-1: The structure and composition of the IRB or EC are appropriate to the amount and nature of the research reviewed and in accordance with requirements of applicable laws, regulations, codes, and guidance.  Standard II-2: The IRB or EC evaluates each research protocol or plan to ensure the protection of participants.  Standard II-3: The IRB or EC approves each research protocol or plan according to criteria based on applicable laws, regulations, codes, and guidance.  Standard II-4: The IRB or EC provides additional protections for individuals who are vulnerable to coercion or undue influence and participate in research.  Standard II-5: The IRB or EC maintains documentation of its activities.

Domain III: Researchers and Research Staff  Standard III-1: In addition to following applicable laws and regulations, Researchers and Research Staff adhere to ethical principles and standards appropriate for their discipline. In designing and conducting research studies, Researchers and Research Staff have the protection of the rights and welfare of research participants as a primary concern.  Standard III-2: Researchers and Research Staff meet requirements for conducting research with participants and comply with all applicable laws, regulations, codes, and guidance; the Organization’s policies and procedures for protecting research participants; and the IRB’s or EC’s determinations.

Summary: Revised Accreditation Standards  Strengthen identification and management of financial conflict of interest  Emphasize international research  Recognize the role of the community  Focus on data and safety monitoring  Elevate importance of resources for the HRPP  Emphasize continuous quality improvement

Is Accreditation Making a Difference?  Quality  Improve protection for research participants  Competency of researchers and research staff  Competency of IRB staff and members  Better relationships between IRB and researcher

Is Accreditation Making a Difference?  Recognition  Peers  OHRP factors accreditation into selection of institutions for not-for-cause oversight evaluations  Sponsor preference for accredited organizations  Collaborations and multi-site research

Is Accreditation Making a Difference?  Compliance  DHHS, FDA, and VA regulations  DoD, DOE, ED, EPA, and DOJ rules  ICH-GCP Guidance (E6)

Analysis of Inspections of Clinical Investigators  January 1, 2008 – December 31, 2008 –219 inspections –Calculated percent of no action indicated, voluntary action indicated, and ordered action indicated by accredited/in process and non-accredited organizations

Clinical Investigator Findings TypeNo Action Indicated Voluntary Action Indicated Ordered Action Indicated N Accredited or in process 73%27%0%30 Non-accredited53%46%<1%

Conclusions  Difference in inspections findings between investigators at accredited and non- accredited organizations is statistically significant (p <.042)  Accreditation is a marker of a higher quality research program

Closing Thoughts  Complimentary functions of accreditation and federal oversight  Reasonable expectations of accreditation  Working together to identify outcomes and quality indicators