IRB Determinations

1
IRB Determinations
2

• 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
• All were addressed in a response sent to AAHRPP
  January 3, 2014
• AAHRPP Accreditation Council meets on March 17,
  2014

3
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

4
IRB Approval

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

5
IRB Approval of Research with ConditionsContinge
nt 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
  investigators response satisfies the IRBs
  conditions, i.e., further review by the convened
  IRB is unnecessary.

6
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.

7
Contingent Approval or Deferral?Whats your
determination?

• 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?

8
Contingent Approval or Deferral?

• 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?

9
Contingent Approval or Deferral?

• 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?

10
Contingent Approval or Deferral?

• 4. 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?

11

• 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 subjects 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.
12
Examples of Serious Noncompliance

• 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

13
IRB Review of Investigator Noncompliance

• 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.

14
Mandatory Reporting to External Agencies

• 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
• Unanticipated problems that involve risks to
  subjects or others
• Suspension or termination of IRB approval

15
Guidance for IRB MotionsNoncompliance
Determinations

• 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