OHRP’s Compliance Oversight Procedures Kristina C. Borror, Ph.D. Division of Compliance Oversight Office for Human Research Protections

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

OHRP’s Jurisdiction Research conducted or supported by HHS Research conducted at an institution holding an applicable Assurance of Compliance

OHRP Compliance Oversight Activities

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

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

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

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

For-Cause Site Visits Findings Meet with the signatory officials on the Assurance, or their designees on last day to describe OHRP’s findings

Compliance Oversight Investigation Possible Determinations/Outcomes (1) Protections under an institution’s Assurance are in compliance Protections under an institution’s 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

Compliance Oversight Investigation Possible Determinations/Outcomes (2) Noncompliance identified, and OHRP approval of Assurance withdrawn OHRP may recommend to appropriate HHS Officials or PHS agency heads that: an institution or investigator be temporarily suspended or permanently removed from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 institution’s or an investigator’s past noncompliance prior to review of new projects

Compliance Oversight Investigation Possible 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.

Common Areas of Noncompliance Identified by OHRP

Common Areas of Noncompliance (1) OHRP Compliance Activities: Common Findings and Guidance - 7/10/02 http://ohrp.osophs.dhhs.gov/references/findings.pdf Borror et al, “A Review of OHRP Compliance Oversight Letters.” IRB: Ethics and Human Research. Sept-Oct 2003; Vol 25 No 5: 1-4.

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

Common OHRP Findings Initial 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

Common OHRP Findings Expedited 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

Common OHRP Findings Informed 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

Common OHRP Findings IRB 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

Common OHRP Finding IRB 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

Common OHRP Finding IRB 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

Underlying Causes of Noncompliance

Underlying Causes of Noncompliance Inadequate education of IRB members, IRB staff, and investigators Inadequate staff and resources for the IRB Overburdened IRBs

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