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Continuing Review

Introduction

DHHS and FDA regulations authorize the IRB to conduct continuing review of research at intervals appropriate to the degree of risk, but not less than once per year [45 CFR Part 46.109(e) and 21 CFR Part 56.109(f)]. At UCI, some minimal risk research that does not require federal oversight may be granted a three year approval.

Initial IRB review is based on the researcher′s best assessment about anticipated results, risk, and procedures. The IRB uses its expertise to judge whether this estimate is reasonable and supportable. The continuing review process is as important as the initial review process. It is only after research has begun that the real risks can be evaluated and the preliminary results used to evaluate the actual risk/benefit ratio.

The risk/benefit ratio may change over time; not only because of unexpected results and effects of the research intervention itself, but because new knowledge resulting from other research may affect the balance. After reassessment, the IRB has the authority to approve, require modifications, suspend, or terminate approval of research that is not being conducted in accordance with the IRB's requirements or that has been associated with unexpected serious harm to subjects [45 CFR Part 46.113]. If approval of a protocol is suspended or terminated, the IRB is required to report its decision promptly to the researcher, the Department Chair, the institutional official, and the appropriate federal department or agency head (or designated office, such as FDA and OHRP). Alternatively, the IRB may impose special precautions or relax special requirements it had previously imposed on the research protocol. For example, the IRB has authority to observe, or have a third party observe, the consent process as well as the research itself [45 CFR Part 46.109(e)].

Before the Full Committee Meeting

As previously discussed in How to Review a New IRB Protocol, HHS regulations 45 CFR 46.111 sets forth the criteria that must be satisfied in order for the IRB to approve research; These criteria include determinations by the IRB regarding risks, potential benefits, informed consent, and safeguards for human subjects. The IRB must ensure that these criteria are satisfied at the time of initial and continuing review. UCI′s IRB uses a primary reviewer system to review Continuing Protocol applications. One IRB member is assigned to review the Continuing Protocol Application and ancillary documents, and present his/her recommendations and concerns to the full Committee.

The Continuing Protocol Application (CPA), essentially a status report on the progress of the research.

All IRB members receive the following:

The CPA includes:

  • The number of subjects enrolled since initial IRB approval and since the last IRB approval;
  • A gender and ethnic breakdown of subject enrollment;
  • A summary of any unanticipated problems involving risks to subjects or others and any withdrawal of subjects from the research or complaints about the research since the last IRB approval;
  • A summary of any UCI adverse events not yet reported to the IRB and a summary of any unanticipated problems that occurred at UCI since last IRB approval;
  • A summary of any relevant recent literature, interim findings, and amendments or modifications to the research since the last approval;
  • Any other relevant information, especially information about risks associated with the research.
  • A copy of the most recent IRB approved informed consent document(s) and assent form(s), if applicable;
  • A copy of the most recent IRB approved protocol narrative;
  • An Adverse Event Report listing all previously reported adverse events (AEs and SAEs) that occurred at UCI and SAEs that occurred at other multi-center locations since initial IRB approval; and
  • A copy of the master protocol, for sponsored clinical research;
  • A summary report of FDA Safety Reports received since initial IRB approval.

In addition, the primary reviewer receives:

  • A copy of the master protocol, for sponsored clinical research and
  • A multi-center trial report and/or Data Safety Monitoring Report, if applicable.

Review the assigned materials at least 2-3 days in advance of the meeting. The primary reviewer is required to thoroughly review the Continuing Protocol Application and all ancillary reports and documents.

Get all questions answered before the meeting. IRB Members are not expected to be the absolute experts about the protocols they are assigned to review. Talk with others as needed. Feel free to contact the:

  • IRB Chair
  • Informal Consultant* (e.g., colleague w/ expertise)
  • Research Protections staff (Administrator, Coordinator)
  • Furthermore, contact the Lead Researcher if you have questions. Collegial interaction between researchers and IRB members facilitates the IRB review process and research compliance as well as fosters respect for human subjects protection and the IRB process.
  • Contact the IRB Chair and Administrator if you have serious concerns about the protocol.

* Informal verbal consultation is encouraged. However, IRB members must uphold the Members Standards by maintaining all committee proceedings and documents that contain personal, confidential and proprietary information in strict confidence. Such information may not be used for any purpose other than the IRB review and may not be disclosed to anyone outside of the IRB unless permission is granted in writing by the Vice Chancellor for Research.

The Process of Reviewing a Continuing Review Application

  • Read the consent document first. The consent document should be in lay language and therefore, should provide a good introduction to the research.
  • Read the Continuing Protocol Application. The continuing application gives a status report of the protocol. Consider the following:
    • Equitable selection of subjects: Is the sample distribution appropriate given the purposes of the research and the setting in which the research is being conducted?
    • Should women, minorities, and children be included in the sample distribution? If yes, are they appropriately represented?
    • Risk/Benefit analysis: Does the updated status report alter the study′s risk/benefit ratio?
    • Based on the risk/benefit assessment determine whether the research may continue, be temporarily suspended or terminated.
    • Did the researcher report any significant new findings that may relate to the subject's willingness to continue participation? This information should be provided to the subject in accordance with HHS regulations at 45 CFR 46.116(b)(5).
    • Data Monitoring: Are there adequate provisions in place for monitoring the data collection to ensure the safety of subjects?
    • Privacy and Confidentiality: Are there adequate provisions in place to protect the privacy of subjects and to maintain the confidentiality of data?
  • Review the ancillary reports (e.g., Adverse Event report, Multi-site report, DSMB report). Does the information provided in the report alter the risk/benefits assessment?
  • Review the protocol narrative. Should the narrative be updated?
  • Read the Consent form again.
    • Does the consent form require updating or change to remain in compliance?
    • Does the updated status report prompt notification of subjects already enrolled (i.e. revised consent process, information sheets, etc.)?
  • Read the Reviewer Checklist: Write comments and recommendations on the Reviewer′s checklist, provide justification, and be prepared to present them to the Committee. Also, review the Administrator′s Comments section and indicate your response to any questions posed to the Committee.

* Adapted from "Institutional Review Board Member Handbook" by Robert Amdur, MD
Jones and Bartlett Publishers, 2003

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