Repositories, Tissue Storage, and Data Banks

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CTSA NICHD Workshop on Comparing IRB Models for
Multi-site Pediatric Research StudiesOHRP
PerspectiveApril 23, 2009

• Julie Kaneshiro and Ivor Pritchard
• HHS Office for Human Research Protections

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Topics

• Current regulatory flexibility
• Cooperative review arrangements
• Designation of IRBs
• OHRP co-sponsored meetings on alternative IRB
  models
• Proposal to hold IRBs directly accountable
• Issues to consider

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Current Regulatory Flexibility

• Cooperative review arrangements for multi-site
  research (45 CFR 46.114)
• Joint IRB review
• Facilitated IRB review
• Reliance on external IRB

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Current Regulatory Flexibility

• Designating IRBs on an FWA
• Internal IRB
• External IRB
• - IRB of another institution
• - Independent or commercial IRB
• Internal and external IRB
• IRB composed of members from both inside and
  outside of the institution

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Current Regulatory Flexibility

• Additional points
• IRBs must be registered to be designated on an
  FWA
• When designating an external IRB an IRB
  Authorization Agreement must be developed

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Meetings on Alternative IRB Models

• Secretarys Advisory Committee on Human Research
  Protections recommendation
• OHRP, NIH, and FDA should consider holding a
  workshop focused on central IRB review mechanisms
  and that SACHRP use the workshop experience and
  other processes as a means of gathering
  information and moving forward toward future
  committee action (Fall, 2004).

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Meetings on Alternative IRB Models

• OHRP co-sponsored meetings on alternative IRB
  models in November 2005 and November 2006
• Other sponsors were NIH, the Association of
  American Medical Colleges, and the American
  Society of Clinical Oncology

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Meetings on Alternative IRB Models

• A key conclusion
• Despite existing regulatory flexibilities some
  institutions remain reluctant to designate
  external IRBs and rely on cooperative review
  arrangements.

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Meetings on Alternative IRB Models

• A key factor
• OHRP currently holds institution engaged in
  human subjects research study accountable for
  noncompliance on the part of the external IRB
  designated on FWA to review the research.

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OHRP Proposal to Hold IRBs Accountable

• Should OHRP revise 45 CFR part 46 to enable HHS
  to hold IRBs and IRB organizations (IORGs)
  directly accountable for compliance?
• An Advanced Notice of Proposed Rulemaking
  published March 5, 2009 (see http//edocket.access
  .gpo.gov/2009/pdf/E9-4628.pdf)
• Comments due by June 3, 2009

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Proposal to Hold IRBs Accountable

• Issues to consider
• FDAs IRB regulations explicitly include
  compliance provisions (21 CFR part 56)
• Is there sufficient need for HHS to pursue a
  regulatory change to 45 CFR part 46 to hold IRBs
  directly accountable?

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Proposal to Hold IRBs Accountable

• Would such a regulatory change have the
  unintended effect of making IORGs less willing to
  have their IRB designated on other institutions
  FWAs?
• How should the IRB authorization agreement be
  used to inform OHRPs compliance oversight
  evaluations?

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Proposal to Hold IRBs Accountable

• How should OHRP categorize the responsibilities
  of the IRB/IORG and FWA holding institution?
• Regulatory requirements seem to fall into three
  categories of responsibilities.

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Proposal to Hold IRBs Accountable

• Categories of regulatory responsibilities
• Responsibilities unique to IRBs/IORGs
• Responsibilities unique to institution engaged in
  human subjects research
• Responsibilities that may be fulfilled by either
  IRBs/IORGs or institutions engaged in human
  subjects research.
• Is there a category of responsibilities that are
  inherently shared by the IRBs/IORGs and engaged
  institutions?

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Proposal to Hold IRBs Accountable

• Responsibilities that may be unique to
  IRBs/IORGs a few examples
• Provisions regarding IRB membership (45 CFR
  46.107)
• Provision that identifies criteria for IRB
  approval of research (45 CFR 46.111)
• Provision that permits IRB to alter or waive
  informed consent (45 CFR 46.116(c) and (d))

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Proposal to Hold IRBs Accountable

• Responsibilities that may be unique to engaged
  institutions a few examples
• Requirement that investigator obtain IRB review
  and approval before beginning non-exempt human
  subjects research (45 CFR 46.109(a))
• Requirement that no investigator conduct
  non-exempt human subjects research without
  obtaining and documenting subjects informed
  consent unless an IRB has waived these
  requirements (45 CFR 46.116 and 46.117).

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Proposal to Hold IRBs Accountable

• Responsibilities that may be fulfilled by
  IRB/IORG or engaged institutions a few examples
• Determining applicability of 45 CFR part 46 (e.g.
  exemptions) (45 CFR 46.101(b))
• Developing written IRB procedures which IRB will
  follow (45 CFR 46.103(b)(4))
• Fulfilling documentation and recordkeeping
  requirements associated with IRB activities (45
  CFR 46.115)

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Resources

• OHRP Assurances webpage http//www.hhs.gov/ohrp/
  assurances/assurances_index.html
• OHRP FWA FAQS http//www.hhs.gov/ohrp/FWAfaq.htm
  l
• OHRP IRB registration FAQS http//www.hhs.gov/oh
  rp/IRBfaq.html
• Reports from 2005 and 2006 meetings on
  alternative IRB models
• http//www.dhhs.gov/ohrp/sachrp/documents/AltModIR
  B.pdf
• http//www.aamc.org/research/irbreview/irbconf06rp
  t.pdf