IRB Determinations 1

AAHRPP Site Visit Results Site visitors observed a real commitment to human subject protections Investigator and research staff opinions of the IRB and OPHS are markedly positive Identified 8 areas of concern o All were addressed in a response sent to AAHRPP January 3, 2014 AAHRPP Accreditation Council meets on March 17,

Areas of Concern 1.Technical resources for IRBear platform 2.Quality improvement activities to assess HRPP compliance and quality, efficiency, and effectiveness 3.IRB determinations of serious and/or continuing noncompliance; reports to regulatory agencies 4.Conflicts of interest – Organizational and individual 5.Control of investigational medical devices 6.Clinical trials agreements (contracts) with sponsors 7.Qualifications and knowledge of IRB chair, vice chairs, and members -- Evaluations and feedback 8.Contingent approvals and deferrals of protocols 3

IRB Approval The IRB must determine that all of the approval criteria are satisfied in accordance with the Common Rule and FDA regulations: 1.Risks are minimized 2.Risks are reasonable in relation to anticipated benefits and the importance of the knowledge to be gained 3.Selection of subjects is equitable 4.Informed consent will be sought 5.Informed consent will be appropriately documented 6.Adequate provision for monitoring the data collected to ensure subject safety 7.Adequate provisions to protect subject privacy and maintain confidentiality of the data 8.Additional safeguards for subjects who are vulnerable to coercion or undue influence and relevant subparts (children, pregnant women, prisoners) 4

IRB Approval of Research with Conditions “Contingent Approval” The IRB requests that the investigator either: Make specified changes to the research protocol or consent documents; Confirm specific assumptions or understandings on the part of the IRB regarding how the research will be conducted; or Submit additional documents such that, based on the assumption that the conditions are satisfied, the IRB is able to make all of the determinations required for approval. The IRB chair or her qualified designee may determine by expedited review that the investigator’s response satisfies the IRB’s conditions, i.e., further review by the convened IRB is unnecessary. 5

IRB Deferral The IRB cannot make one or more of the determinations required for approval under the regulations. Information in the research protocol is insufficient for the IRB to determine if one or more approval criteria have been adequately met; and The IRB is unable to specify changes to the research protocol that would allow the IRB to make the required determinations The IRB requires that the investigator either: Make changes to the protocol or consent documents; or Submit clarifications or additional documents The convened IRB must review and approve the revised research project. 6

Contingent Approval or Deferral? What’s your determination? 7 1. The convened IRB requires the investigator to do the following: Re-locate in the informed consent document the statement,“You will receive $500 for participating in this study,” from the Benefits section of the form to a separate section titled Compensation. Should the IRB “approve with contingencies” or “defer” final review?

Contingent Approval or Deferral? 8 2. The convened IRB requires the investigator to do the following: Provide a justification for using a placebo and withholding currently available treatment for a serious medical condition for subjects assigned to the control group. Should the IRB “approve with contingencies” or “defer” final review?

Contingent Approval or Deferral? 9 3. The convened IRB requires the investigator to do the following: Clarify whether individuals who have taken aspirin within 14 days prior to enrollment will be excluded from the study because of concerns about the risks of bleeding. Should the IRB “approve with contingencies” or “defer” final review?

Contingent Approval or Deferral? The convened IRB requires the investigator to do the following: Add “a history of aspirin use in the past 14 days” to the exclusion criteria for subject enrollment in the research protocol. Should the IRB “approve with contingencies” or “defer” final review?

Serious and Continuing Noncompliance Noncompliance – Failure to abide by the regulations, institutional policies and procedures, or IRB requirements or determinations. Serious noncompliance – Noncompliance that may impact subject safety, increase risks to subjects, affect integrity of the data, violate a subject’s rights or welfare, or affect subjects’ willingness to participate in the study. Continuing noncompliance – Series of noncompliant actions or omissions taken by an investigator or study staff, in reasonably close proximity, which indicates the need for evaluation of the methods and systems used to protect human subjects. 11

Examples of Serious Noncompliance 12 Failure to notify the IRB of changes in approved procedures Continuation of research activities following protocol expiration Failure to adequately protect participant privacy and confidentiality of data Failure to conduct research according to the IRB approved protocol Failure to follow proper accountability procedures for an investigational drug

IRB Review of Investigator Noncompliance 13 The fully convened IRB must make a formal determination whether an event constitutes serious and/or continuing noncompliance A motion should be made and a vote taken on the determination The meeting minutes should include the motion and outcome of the vote.

Mandatory Reporting to External Agencies 14 Serious or continuing noncompliance must be reported to the appropriate Federal Department or Agency head if the research is federally funded or involves FDA-regulated products. Other events that must be reported are: o Unanticipated problems that involve risks to subjects or others o Suspension or termination of IRB approval

Guidance for IRB Motions: Noncompliance Determinations 15 Acknowledge or Defer (see handout) If a final determination of serious and/or continuing noncompliance is made, the IRB must specify whether the noncompliance requires reporting to an external agency such as the study sponsor, OHRP, or the FDA The IRB also may defer its final determination and require an additional response or action on the part of the investigator to resolve the issue