Element II.2.E.

Element II.2.E.1. – Initial review
Element II.2.E.2. – Continuing review
Element II.2.E.3. – Review of proposed modifications to previously approved research

The IRB or EC should have policies and procedures that describe the review of research at convened meetings, including initial review, continuing review, and review of modifications to previously approved research.

The IRB or EC should obtain and review sufficient information to conduct initial review of research, continuing review, and review or modifications to previously reviewed research in accordance with the regulations and the organization’s written materials. When they are scheduled to attend an IRB or EC meeting, all members (including alternate members) should review enough information so that they will be able to determine whether the research meets the regulatory criteria for approval.

Written materials should describe the information provided to all IRB or EC members and the information provided to all primary reviewers with the expectation that IRB or EC members will review the materials and the primary reviewer will conduct an in-depth review. When an organization has an electronic system that provides members access to materials, policies and procedures should describe what information primary reviewers are expected to review and what information all other members are expected to review.

When the convened IRB or EC requires modifications to research to secure approval (sometimes referred to as “approval with conditions” or “conditional approval” or “contingent approval”), verification of those modifications may be made by a staff member or IRB or EC member designated by the IRB or EC chair, or by the IRB or EC chair. Verification of modifications is not considered review using an expedited procedure. When the IRB or EC grants conditional approval, the IRB or EC should provide the researcher specific modifications required to secure approval. For example, “Participants must be 18 years or older” or “Drop the placebo controlled arm of this study.”

The convened IRB or EC should not grant approval contingent upon clarifications or modifications directly relevant to criteria for approval specified in regulations. Such requests include: “Explain why participants younger than 18 years of age will be allowed to participate,” “Provide additional justification for the use of placebo,” or “Clarify whether

participants will be offered counseling services at the end of the study.” The convened IRB or EC should review responses to requests for substantive modifications relevant to the criteria for approval.

An IRB or EC serving as a single IRB for a multi-site study, should have a policy and procedure for reviewing the addition of investigative sites to previously approved protocols. When serving as a single IRB for a multi-site study, the independent the IRB or EC may decide to review these additions as separate protocols or as modifications to previously approved research, and they may decide to handle such modifications using the expedited procedure rather than the convened IRB or EC for review. When the expedited procedure is used, the independent IRB or EC written materials should specify the criteria for when the addition of an investigative site is considered to be a minor modification.

Regulatory and guidance references

DHHS: 45 CFR 46.103, 45 CFR 46.108(b), 45 CFR 46.109, OHRP Guidance on Written Institutional Review Board (IRB) Procedures, OHRP Guidance on Continuing Review, OHRP Guidance on IRB Approval of Research with Conditions
DoD: Instruction 3216.02 4.b.4
FDA: 21 CFR 50.25(b)(5), 21 CFR 56.108(a), 21 CFR 56.109, FDA Information Sheets: Continuing Review After Study Approval, Frequently Asked Questions: IRB Procedures
ICH-GCP: 3.2.2, 3.2.3, 3.3.3, 3.3.4
VA: VHA Directive 1200.05(3) section 5 and 1200.05(3) section 9
AAHRPP Tip Sheet: Following the Guideline of the International Conference on Harmonisation – Good Clinical Practice (E6)
AAHRPP Tip Sheet: Review of Research by the Convened IRB or EC

Required written materials

Essential requirements:
1. Policies and procedures describe the process the IRB or EC uses to review research for initial review, continuing review, and review of modifications to previously approved research:
  1. The primary reviewer system used, if any.
  2. The process used to supplement the IRB’s or EC’s review.
  3. The range of possible actions that the IRB or EC is allowed to take.
  4. If the IRB approves research with conditions:
    1. Substantive changes or requirements, requests for more information for IRB consideration, and other issues related to the criteria for approval require review and approval by the convened IRB or EC.
    2. Minor or prescriptive changes or requirements may be reviewed for approval by a staff member or IRB or EC member designated by the IRB or EC chair, or by the IRB or EC chair.
    3. Written materials describe how the date of approval is calculated, consistent with applicable law, regulations, and guidance.
  5. Written materials describe a process for the IRB or EC to determine which protocols need review more often than annually. The IRB or EC should consider:
    1. The nature of and any risks posed by the clinical investigation.
    2. The degree of uncertainty regarding the risks involved.
    3. The vulnerability of the participants.
    4. The experience of the clinical investigator in conducting clinical research.
    5. The IRB’s or EC’s previous experience with that researcher or sponsor (e.g., compliance history, previous problems with the researcher obtaining informed consent, prior complaints from participants about the researcher).
    6. The projected rate of enrollment.
    7. Whether the study involve novel therapies.
  6. For initial review of research by a convened IRB, policies and procedures indicate that when they are scheduled to attend an IRB or EC meeting, all members (including attending alternate members) are provided and review:
    1. The full protocol, application, or a protocol summary containing the relevant information to determine whether the proposed research fulfills the criteria for approval.
    2. Proposed consent document.
    3. Recruitment materials.
    4. At least one member is provided and reviews the investigator’s brochure (when one exists).
  7. For continuing review of research by a convened IRB or EC, policies and procedures indicate that, when they are scheduled to attend an IRB or EC meeting, all IRB or EC members (including alternate members) are provided and review:
    1. The full protocol, application, or a protocol summary containing the relevant information necessary to determine whether the proposed research continues to fulfill the criteria for approval.
    2. The current consent document.
    3. Any newly proposed consent document.
    4. A status report on the progress of the research.
  8. For continuing review of research by a convened IRB or EC, policies and procedures indicate that at least one IRB or EC member is provided and reviews the complete protocol including any protocol modifications previously approved by the IRB or EC.
  9. The status report on the progress of the research includes:
    1. The number of participants accrued.
    2. A summary since the last IRB review of:
      1. Adverse events and adverse outcomes experienced by participants.
      2. Unanticipated problems involving risks to participants or others.
      3. Participant withdrawals.
      4. The reasons for withdrawals.
      5. Complaints about the research.
      6. Amendments or modifications.
      7. Any relevant recent literature.
      8. Any interim findings.
    3. Any relevant multi-center trial reports.
    4. The researcher’s current risk-potential benefit assessment based on study results.
  10. Policies and procedures have the IRB or EC use the required criteria for approval for all reviews of research, including initial review, continuing review, and review of a modification to previously approved research (when the modification affects a criterion for approval).
  11. Policies and procedures have the IRB or EC determine whether continuing review should occur at an interval less than one year, when continuing review is required.
  12. Policies and procedures describe:
    1. Whether the expiration date is the last date that the protocol is approved or the first date that the protocol is no longer approved.
    2. The calculation of the expiration date.
  13. If the IRB approves research with conditions:
    1. Substantive changes or requirements, requests for more information for IRB consideration, and other issues related to the criteria for approval require review and approval by the convened IRB or EC.
    2. Minor or prescriptive changes or requirements may be reviewed for approval by a staff member or IRB or EC member designated by the IRB or EC chair, or by the IRB or EC chair.
  14. Written materials describe how the date of approval is calculated, consistent with applicable law, regulations, and guidance.
    1. If the research expires before the conditions are reviewed and approved, written materials:
      1. Have all research activities stop.
      2. Have interventions and interactions on current participants stop, unless the IRB or EC finds an over-riding safety concern or ethical issue involved such that it is in the best interests of individual participants to continue participating.
      3. Do not allow new enrollment of participants to occur.
  15. Policies and procedures describe:
    1. The organizational offices and officials who are notified of the findings of the IRB or EC and the method of notification.
    2. The person or office that is responsible for further approval or disapproval of research that is approved by the IRB or EC.
    3. The process the IRB or EC uses for reporting its findings and actions to researchers in writing, including:
      1. The decision to approve, disapprove, or require modifications to secure approval.
      2. Any modifications or clarifications required by the IRB as a condition for IRB approval.
      3. If an IRB decides to disapprove a research activity, a statement of the reasons for its decision and giving the researcher an opportunity to respond in person or in writing.
      4. The review of researchers’ responses.
  16. For continuing review of research, policies and procedures have the IRB or EC determine:
    1. That the protocol needs verification from sources other than the researchers that no material changes had occurred since previous IRB or EC review.
    2. That the current consent document is still accurate and complete.
    3. That any significant new findings that arise from the review process and that might relate to participants’ willingness to continue participation will be provided to participants.
  17. If a researcher does not provide continuing review information to the IRB or EC or the IRB or EC has not approved a protocol by the expiration date, written materials:
    1. Have all research activities stop.
    2. Have interventions and interactions on current participants stop, unless the IRB or EC finds an over-riding safety concern or ethical issue involved such that it is in the best interests of individual participants to continue participating.
    3. Do not allow new enrollment of participants to occur.
  18. For review of modifications to previously approved research by a convened IRB or EC, policies and procedures indicate that, when they are scheduled to attend a meeting, all members (including alternate members) receive and review all modified documents.
  19. Policies and procedures have:
    1. The IRB or EC use the criteria to approve modifications to previously approved research when the modifications affect one or more criteria.
    2. The IRB or EC determine that any significant new findings that arise from the review process and that might relate to participants’ willingness to continue participation are provided to participants.
    3. Changes in approved research that are initiated without IRB or EC approval to eliminate apparent immediate hazards to the participant:
      1. Are promptly reported to the IRB or EC.
      2. Are reviewed by the IRB or EC to determine whether each change was consistent with ensuring the participants’ continued welfare.
    4. Researchers report to the IRB or EC proposed changes in a research study.
    5. Researchers report to the IRB or EC the premature completion of a study.
  20. Policies and procedures describe actions taken to ensure that proposed changes in approved research during the period for which IRB or EC approval had already been given cannot be initiated without IRB approval.
When following DoD requirements:
1. Surveys performed on DoD personnel must be submitted, reviewed, and approved by the DoD Information Management Control Officer (IMCO) after the research protocol is reviewed and approved by the IRB. When a survey crosses DoD components, additional review is required.
  1. Policies and procedures must specifically indicate whether the organization conducts research on DoD personnel, and if such research is allowed, describe who in the organization is responsible for obtaining approval and the process they go through.
2. For DoD-supported research, the following must be promptly (AAHRPP defines “promptly” as within 30 days) reported to the COHRP:
  1. When significant changes to the research protocol are approved by the IRB or EC:
    1. Changes to key investigators or institutions.
    2. Decreased benefit or increased risk to participants in greater than minimal risk research.
    3. Addition of vulnerable populations as participants.
    4. Addition of DoD-affiliated personnel as participants.
  2. Change of reviewing IRB.
  3. When the organization is notified by any federal body, state agency, official governing body of a Native American or Alaskan native tribe, other entity, or foreign government that any part of an HRPP is under investigation for cause involving a DoD-supported research protocol.
  4. Any problems involving risks to participants or others, suspension or termination of IRB approval, or any serious or continuing noncompliance pertaining to DoD-supported human participant research.
  5. The results of the IRB’s continuing review, if required.
  6. Change in status when a previously enrolled participant becomes pregnant, or when the researcher learns that a previously enrolled participant is pregnant, and the protocol was not reviewed and approved by the IRB in accordance with 45 CFR 46, Subpart B.
  7. Change in status when a previously enrolled participant becomes a prisoner, and the protocol was not reviewed and approved by the IRB in accordance with 32 CFR 219, Subpart C.
  8. Closure of a DoD-supported study.
When following VA requirements:
1. Policies and procedures indicate that if a researcher does not provide continuing review information to the IRB or the IRB has not approved a protocol by the expiration date:
  1. The researcher must stop all research activities including, but not limited to, enrollment of new participants, analysis of individually identifiable data, and research interventions or interactions with currently enrolled participants, except where stopping such interventions or interactions could be harmful to participants.
  2. The researcher must immediately submit to the IRB chair a list of research participants who could be harmed by stopping study procedures.
  3. The IRB chair, with appropriate consultation with the VA facility chief of staff, determines within two business days whether participants on the list may continue participating in the research interventions or interactions.

Common types of materials that may be used to meet the element

Reviewer checklist
Template letters for notifications

Outcomes

All IRB or EC members (including alternate members) review materials in enough depth to discuss the information when they are present at the convened meeting.
At least one IRB or EC member conducts an in-depth review of all submitted materials.
IRB or EC members can obtain information provided to any individual reviewer.
Each approved research protocol or plan meets the required criteria for approval.
The approval period for research is no longer than one year, when continuing review is required.
The IRB or EC communicates its findings to the organization and researchers.

Proceed To: Element II.2.F.

Resources: For Accreditation - Evaluation Instrument

Evaluation Instrument for Accreditation

Table of Contents

Element II.2.E.