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Continuing Review Process

Federal Requirements for Continuing Review

Except for human research studies that have been granted Exempt registration, DHHS and FDA regulations requires the IRB to continually review ongoing research at intervals appropriate to the potential risk to participants, but at least annually.

While initial IRB review is based on the researcher's best assessment of the anticipated benefits, risk, and procedures, the continuing review process is important because it is based on the conduct of the study; actual risk can be evaluated and preliminary results used to assess the risk/benefit ratio. In addition, the risk/benefit ratio may change not only because of unexpected results and effects of the research intervention itself, but because new knowledge resulting from related research may affect the balance.

Per OHRP, continuing review must be substantive and meaningful. The criteria to grant continuing IRB approval are the same criteria required for initial IRB approval of the research (45 CFR 46.111 and 21 CFR 56.111)

  • Risks to subjects are minimized.
  • Risks to subjects are reasonable in relation to anticipated benefits.
  • Selection of subjects is equitable.
  • Informed consent will be sought.
  • Informed consent will be appropriately documented.
  • When appropriate... adequate provision for monitoring the data.
  • When appropriate... adequate provisions to protect the privacy and confidentiality.
  • Appropriate safeguards have been included to protect vulnerable subjects.

Per OHRP and FDA, when conducting continuing review of the research the IRB must be provided with the following information:

  • The number of participants enrolled;
  • A summary of adverse events and any unanticipated problems involving risks to participants
  • The number of participants that have withdrawn including the reasons;
  • A summary of any complaints about the research;
  • A summary of any relevant recent literature, interim findings, and modifications to the research since the last review;
  • A current risk/benefit assessment based on the existing study results;
  • Any other relevant information, especially information about risks associated with the research; and
  • A copy of the current informed consent document.

After reassessment of the research at Continuing review, 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 participants [45 CFR 46.113 and 21 CFR Part 56.113].

If approval of the research 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 additional precautions or reassess special requirements it had previously imposed on the research. For example, the IRB has authority to observe, or have a third party observe, the consent process as well as the research itself. The IRB determines the frequency of continuing review (at least annually) for each study based on the complexity and risk involves in the study adequate to assure the continued protection of the rights and welfare of research participants.

Continuing Review of Studies Meeting Expedited Criteria

In general, studies that qualify for expedited review will receive annual continuing review; however, some studies may qualify for Extended IRB Approval and would undergo continuing review every three years. For more information on Extended IRB Approval please see the following: Extended IRB Approval.

Under category 45 CFR 46.110(F)(8), an expedited review procedure may be used for the continuing review of research previously approved by the convened IRB as follows:

  • the research is permanently closed to the enrollment of new subjects;
  • all subjects have completed all research-related interventions; and
  • the research remains active only for long-term follow-up of subjects;

OR

  • no subjects have been enrolled; and
  • no additional risks have been identified;

OR

  • the remaining research activities are limited to data analysis.

Under category 45 CFR 46.110(F)(9), an expedited review procedure may also be used for the continuing review of research previously approved by the full Committee when the research is not conducted under an investigational new drug application (IND) or investigational device exemption (IDE) where categories two (2) through eight (8) do not apply but the IRB has determined and documented at a convened meeting that the research involves no greater than minimal risk and no additional risks have been identified.

IRB Approval Period

Federal regulations make no provision for any grace period extending the conduct of research beyond the expiration of IRB approval. Therefore, continuing review and re-approval of research must occur on or before the date when IRB approval expires. Investigators are responsible for submitting a continuing protocol application and maintaining current IRB approval (or exempt registration) until all of the following occur:

  • Subject recruitment has concluded (i.e., no subject recruitment is in progress or anticipated)
  • All subject specimens, records, data have been collected (i.e., no further collection of data/information from or about living individuals is needed)
  • All interactions or interventions with subjects are completed (i.e., no further contact with subjects is necessary or anticipated)
  • Analyses of subject identifiable data, records, specimens are finished (i.e., use or access to subject identifiable data is no longer necessary.

Note: Investigators performing industry-sponsored research should discuss study closure with the study sponsor or Clinical Research Organization before formally closing human research studies with the IRB. Once a study is closed all data collection and analysis of subject identifiable data and review of source documentation must stop.

Expiration and Lapses in IRB Approval

Investigators must plan ahead to meet required continuing review dates. If an investigator fails to submit an electronic Continuing Protocol Application (CPA) to the IRB or the IRB does not approve continuation of the research before the date of expiration, the research must stop. All of the following research procedures must stop:

  • Subject recruitment or enrollment
  • Collection of data/information from or about living individuals
  • All research-related interventions or interactions with currently enrolled subjects*
  • Data analyses involving subject identifiable data

*Exception: Research-related interventions or interactions with currently enrolled subjects can continue only if stopping the research would jeopardize the rights or welfare of current subjects. The IRB must make this determination and decide which subjects should continue with the intervention during the lapse. A request for such an exception must be made in the writing to the IRB by the Lead Researcher.

Failure to maintain current approval may disqualify data intended for submission to the FDA (e.g., studies of investigational drugs and devices), other federal agencies, and sponsors. It may also result in embargo of data collected during a lapse of approval. Performance of study procedures during lapses in approval also may result in regulatory committee (IRB) sanctions.

Timing to Avoid Expiration of Approval

As a courtesy, the Human Research Protection Program sends the Lead Researcher and Administrative Contact an e-mail reminder to submit for continuing approval. The e-mail reminder is sent 90 days prior to the expiration date for full committee studies and 60 days prior to expiration for expedited studies.

It is strongly recommended that investigators submit their CPA and the required hard copy documentation to ORA at least 60 - 90 days prior to expiration for full Committee studies and 30 days prior to expiration for expedited studies.

Continuing Review Submission Process

All Continuing Protocol Applications must be submitted to the IRB online using the protocol application module (CPA). To complete the CPA, go to http://apps.research.uci.edu/irbcpa. Make sure to upload all required documentation. The protocol narrative and consent/assent forms do not need to be submitted with the CPA. The Human Research Protections staff will provide the latest approved versions of these documents to the IRB.

Your CPA will not be considered for IRB review until the following documents are provided to UCI IRB:

  • If the CPA submission requires additional documentation, make sure to electronically upload all relevant documentation. Additional documentation that may be submitted at the time of renewal includes, but is not limited to, offsite IRB approval letters, updated letters of permission, AE summary reports, multi-site progress report, data safety monitoring report, etc.
  • A signed CPA (electronic or hard copy). Print the PDF of the CPA. Obtain signatures of the Lead Researcher, Department Chair or ORU Director, and Faculty Sponsor (if applicable). Please note that the signed CPA may be delivered to the Office of Research, 141 Innovation Drive, Suite 250, Irvine, CA 92697-7600 (Zot Code 7600), sent via email to: irb@rgs.uci.edu or faxed to: 949-824-3400.

Other Considerations:

  • All prerequisite UCI Reviews must be completed before the CPA will be reviewed.
  • There are no formal submission deadlines for Expedited Review. They are reviewed on a rolling basis; usually within 2-4 weeks. Investigators should plan their submissions accordingly to avoid expiration of IRB approval.
  • There are submission deadlines for Full Committee Reviews. All required hard copy documentation must be received by 5 pm on the deadline day to be considered for the IRB meeting agenda. Investigators should plan their submissions accordingly to avoid expiration of IRB approval.

Seven-Year De Novo Review Requirement

In order to ensure that research protocols continue to meet current regulatory and institutional standards, for protocols involving greater than minimal risk, every seven years, protocols will be required to undergo a "Seven-Year De Novo Review."

This will include the following:

  • An updated protocol narrative – Complete the most current version of the protocol narrative template form available at the IRB Forms page and submit electronically with the CPA; and
  • Updated consent/assent and/or study information sheet(s) – review the most recently approved consent/study information sheet(s) to ensure that they meet the most current document requirements and submit them electronically with the CPA. The templates are available at the IRB Forms page and requirements are available at the Drafting the Informed Consent Form page.
  • The most recent Sponsor/Master Protocol (clinical investigations only).
  • All documentation for the protocol review such as any data collection instruments, recruitment materials, etc. This includes re-submission of any applicable IRB appendices. The appendices are available for downloading under Applications and Forms. These documents should be submitted electronically with the CPA.

The Lead Researcher and Administrative Contact listed on the protocol will receive an auto-generated seven-year reminder memo explaining the Seven-Year De Novo review requirement via email approximately 90 days prior to the expiration date.

During the IRB’s Seven-Year De Novo review(s), the IRB will require that all documents be incorporated into the CURRENT UCI templates. This may involve providing new information that has not been previously requested and therefore, not previously reviewed by the IRB. As with any review, studies are subject to meet all current regulatory requirements, UC/ UCI policies and procedures. As per any Continuing Review, Lead Researchers should not assume that a Seven-Year De Novo continuing review will receive automatic approval. Accordingly, Lead Researchers are asked to follow the submission timeline guidelines especially for Seven-Year De Novo reviews to help avoid a lapse in IRB approval.

Exceptions to the Seven-Year De Novo Review Requirement:

Protocols that do not require Seven-Year De Novo Review:

  1. Research that involves no greater than minimal risk (e.g., protocols that underwent an expedited review)
  2. Continuing review of greater than minimal risk research where:
    • the research is permanently closed to the enrollment of new subjects;
    • all subjects have completed all research-related interventions; and
    • the research remains active only for long-term follow-up of subjects; or
  3. Continuing review of greater than minimal risk research where the remaining research activities are limited to data analysis.

Important Information Regarding Modification Requests

  • If changes need to be made to the research study the investigators must submit a Mod Request.
  • If a modification request is received after submission of the CPA, it will not be reviewed by the IRB until continuing IRB approval is granted.
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