OHRPs Compliance Oversight Procedures

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OHRPs Compliance Oversight Procedures

Kristina C. Borror, Ph.D. Division of Compliance
Oversight Office for Human Research Protections
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Presentation Overview

• OHRP compliance oversight activities
• Common areas of noncompliance identified by OHRP
• Underlying causes of noncompliance
• Solutions to correct/prevent noncompliance

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OHRPs Jurisdiction

• Research conducted or supported by HHS
• Research conducted at an institution holding an
  applicable Assurance of Compliance

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OHRP Compliance Oversight Activities
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Compliance Oversight Investigation

• Receive allegation of noncompliance
• Determine OHRP jurisdiction
• Written inquiry to appropriate institutional
  officials
• Review of institution report and relevant IRB
  documents
• Additional correspondence/telephone
  interviews/site visit as needed
• Issue final determinations

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For-Cause Site Visits

• When does OHRP conduct a site visit? Based on
• nature and severity of the allegations
• evidence of systemic problems
• appropriateness of any corrective actions taken
• perceived need for more in-depth discussions with
  institution staff

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For-Cause Site Visits

• Interviews with--
• institutional administrator(s)
• IRB Chairperson(s)
• IRB members
• IRB staff
• investigators who conduct human subjects research
  
• others as appropriate

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For-Cause Site Visits

• Record Reviews
• OHRP selects 50-75 active protocols for review of
  entire IRB record on-site
• last 25 protocols approved by the IRB under an
  expedited review procedures
• last 25 amendments approved by the IRB under an
  expedited review procedure
• Protocols determined to be exempt during the past
  6 months
• minutes for all IRB meetings for last 4 years

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For-Cause Site Visits

• Findings
• Meet with the signatory officials on the
  Assurance, or their designees on last day to
  describe OHRPs findings

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Compliance Oversight InvestigationPossible
Determinations/Outcomes (1)

• Protections under an institutions Assurance are
  in compliance
• Protections under an institutions Assurance are
  in compliance, but recommended improvements have
  been identified
• Noncompliance identified, and corrective actions
  required
• Noncompliance identified, and Assurance
  restricted pending required corrective actions

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Compliance Oversight InvestigationPossible
Determinations/Outcomes (2)

• Noncompliance identified, and OHRP approval of
  Assurance withdrawn
• OHRP may recommend to appropriate HHS Officials
  or PHS agency heads that
• an institution or investigator be temporarily
  suspended or permanently removed from
  participation in specific project
• peer review groups be notified of an
  institutions or an investigators past
  noncompliance prior to review of new projects

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Compliance Oversight InvestigationPossible
Determinations/Outcomes (3)

• OHRP may recommend that institutions or
  investigators be declared ineligible to
  participate in HHS-supported research
  (Debarment). Debarment will be initiated in
  accordance with procedures specified at 45 CFR
  Part 76.

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Common Areas of Noncompliance Identified by OHRP
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Common Areas of Noncompliance (1)

• OHRP Compliance Activities Common Findings and
  Guidance - 7/10/02
• http//ohrp.osophs.dhhs.gov/references/findings.pd
  f
• Borror et al, A Review of OHRP Compliance
  Oversight Letters. IRB Ethics and Human
  Research. Sept-Oct 2003 Vol 25 No 5 1-4.

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Common Areas of Noncompliance (2)

• Initial and continuing IRB review
• Expedited IRB review procedures
• Reporting of unanticipated problems
• IRB review of protocol changes
• Informed consent
• IRB membership, expertise, staff, support, and
  workload
• Documentation of IRB procedures, activities, and
  findings

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Common OHRP FindingsInitial and Continuing IRB
Review

• Insufficient information to make determinations
  required under 45 CFR 46.111
• Inadequate review at convened meetings
• No substantive continuing review
• Failure to conduct continuing review at least
  annually
• Lack of quorum at convened meetings
• Research conducted without IRB review

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Common OHRP FindingsExpedited Review

• Inappropriate use of expedited review for initial
  and continuing review
• Inappropriate use of expedited review for
  protocol modifications
• Failure to advise full IRB of expedited approvals

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Common OHRP FindingsInformed Consent

• Failure to include all required elements of
  informed consent 45 CFR 46.116(a)
• Failure to include additional elements of
  informed consent when appropriate 45 CFR
  46.116(b)
• Underestimation of risks/overestimation of
  potential benefits
• Language too complex
• Exculpatory language

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Common OHRP FindingsIRB Membership, Expertise,
Support

• Lack of diversity of IRB membership
• Lack of IRB expertise regarding research with
  children
• Lack of prisoner/prisoner representative on IRB
  for review of research with prisoners
• IRB Chair/members lack sufficient understanding
  of HHS regulations
• Inadequate resources

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Common OHRP FindingIRB Policies, Procedures and
Findings (1)

• Inadequate IRB records
• Inadequate IRB minutes
• Failure of IRB to consider additional safeguards
  for vulnerable subjects
• Failure of IRB to make required findings when
  reviewing research involving children

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Common OHRP FindingIRB Policies, Procedures and
Findings (2)

• Failure of IRB to make and document required
  findings for waiver of informed consent
• Failure to make required findings for IRB waiver
  of a signed informed consent document
• Lack of appropriate written IRB policies and
  procedures

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Underlying Causes of Noncompliance
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Underlying Causes of Noncompliance

• Inadequate education of IRB members, IRB staff,
  and investigators
• Inadequate staff and resources for the IRB
• Overburdened IRBs

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Solutions to Correct/Prevent Noncompliance

• Education
• Adequate IRB staff and resources
• Adequate number of IRBs
• Adequate IRB documentation (in particular,
  adequate minutes of IRB meetings)
• Periodic self-assessment of institutional system
  for protecting human subjects