SOP #22 Modifications to Previously Approved or Exempt Research

Owner: Vice President of Academic Affairs
Author: CSS IRB
Contact: irb@css.edu
Policy Number: 22
Effective Date: 10/8/2021

Policy

The CSS IRB must follow written procedures for ensuring prompt reporting to the IRB of proposed modifications in a research activity, and ensuring that changes in approved research, during the period for which IRB approval has already been given, may not be initiated without IRB review and approval except where necessary to eliminate apparent immediate hazards to the human subjects (45 CFR 46.108(a)(3)iii), 21 CFR 56.108(a)(3)).

Purpose

The purpose of this Standard Operating Procedure (SOP) is to describe the process and requirements Investigators use when modifications are made to IRB approved research activity.  This SOP also describes the process and requirements that the CSS IRB must follow when reviewing any and all modifications to an already approved research study and/or exempt study.

Definitions

Modification means any change. It encompasses two commonly used terms:

  • A revision is a change in something that exists, such as increasing the number of participants.
  • An amendment adds something new, such as a person who will obtain informed consent. A key determination is whether an amendment is minor, and thus can be reviewed via the expedited mechanism, or substantive, in which case the convened IRB must review and approve it. Unfortunately, the regulations do not provide a definition of minor or major and substantive changes.

Examples of minor changes (generally can be reviewed via Expedited Review) and major substantive changes (generally reviewed by Full Committee pending upon the overall risk level) to previously approved protocols follow:

Minor Changes:

  • Administrative changes
  • Minor consent form changes
  • Minor changes to recruitment procedures, recruitment materials or submission of new recruitment materials to be used in accordance with approved recruitment methods
  • Minor changes to study documents such as surveys, questionnaires or brochures
  • New study documents to be distributed to or seen by subjects that are similar in substance to those previously approved
  • Changes in payment to subjects or the amount subjects are paid or compensated that are not significant enough to affect the risk/benefit ratio of the study
  • Decrease in the number and volume of sample collections as long as they do not negatively alter the risk/benefit ratio of the study
  • Editorial changes that clarify but do not alter the existing meaning of a document
  • Addition of or changes in study personnel
  • Addition of a new study site (in many but not all cases)
  • Translations of materials already reviewed and approved by the IRB.

Major (Substantive) Changes:

  • Changes that adversely affect the risk/benefit ratio of the study or specifically increase the risk to subjects
  • Changes in inclusion/exclusion criteria that impact the risk/benefit ratio of the study
  • Significant changes in study design, such as the addition of a new subject population or the elimination of a study arm
  • New risk information that is substantial or adversely affects the risk/benefit ratio of the study
  • Significant changes to the study documents to be distributed to or seen by subjects
  • New study documents to be distributed to or seen by subjects that include information or questions that are substantively different from materials already approved by the IRB
  • New or revised financial conflict of interest management plans (e.g., change in PI or change to study design).

IMPORTANT NOTE: These examples may be used as guidance for investigators, but the IRB will make the final determination of appropriate review level.

Level of Review and Type of Modification

Full Committee Review:

Amendments that do not meet the criteria for expedited review must be reviewed by the Full Committee at a convened meeting. Researchers should allow approximately a month for a Full Committee review and approval of a major amendment.

Expedited Review:

Amendments that meet the criteria for expedited review will be reviewed by the Chair or Chair designee according the Expedited Review procedures (See, CSS IRB SOP #11, Expedited Review Procedure and Checklist ). Researchers should allow approximately one week for an expedited review and approval of a minor amendment reviewed by the expedited process. Amendments to protocols that were initially reviewed using the Expedited procedures or by Full Committee may be reviewed by Expedited Review if the amendment fulfills the criteria below:

  1. Protocols Initially Approved by Expedited Review process That May Be Reviewed as Expedited
    1. The amendment continues to pose no more than minimal risk to subjects.
    2. The amendments do  not involve any procedures that do not meet Expedited categories 1 through 7 (see below).
  2. Protocols Initially Approved by Full Committee Review that may be reviewed as Expedited
    1. Amendments do not pose an increased risk to subjects; AND
    2. Amendments constitute a minor change to previously approved research (see examples below).
    3. Any added procedure must fall within Categories 1 through 7 or research that may be reviewed using the expedited procedure.
  3. Protocols Determined by the CSS IRB as Exempt
    1. Any modification to an exempt research project must be submitted to the IRB for review and re-determination of exemption status prior to initiating the changes to the research.
    2. In some circumstances, modifications to exempt research may disqualify the research from the exempt status.

Investigator Responsibilities

Investigators who wish to make alterations to an IRB-approved protocol must submit an amendment form to the IRB via the IRBNet system, prior to initiation of the alteration.  The only exception is a change necessary to eliminate apparent immediate hazards to the research subjects. In such a case, the IRB should be promptly informed of the change following its implementation and should review the change to determine that it is consistent with ensuring the subjects' continued welfare. The form must be completed to include a written description of the proposed change(s) and the reason for the change(s). The amendment form must include all new and/or revised study documents that would be affected by the proposed change(s) (i.e., consent form, questionnaires, scripts, etc.).  If the proposed change(s) affects the application, the amendment form must include an uploaded revised application.

The IRB will reassess the balance of risks to benefits in light of the proposed change and may require the research to be modified or terminated. Only those individuals noted as Principal  Investigator or Co-Investigator have the authority to submit change requests on his or her protocol.

The investigator must determine if the amendment significantly alters the basic design of the study or changes the risk/benefit ratio for participants.  Amendments that alter the research method design that increases the risk/benefit ratio will be reviewed by the convened IRB.  If the risk/benefit ratio has changed, the investigator must also determine whether participants currently and/or previously enrolled on the study will be re-consented. The investigator will need to amend the currently approved informed consent document(s) to reflect the change. In addition, when reviewing information relating to protocol changes, the IRB is required to assess whether the information should be provided to the participants, when such information might affect their willingness to continue to take part in the research.

The investigator must also assure that any change to conflict of interest has been disclosed and reviewed.

IRB Responsibilities

Requests for change(s) are reviewed by the IRB to determine whether the research, if modified, still meets the regulatory criteria for approval.  The same criteria for approval apply to reviews conducted via expedited review as to those conducted by the convened board.

The IRB Chair or experienced designated IRB member may utilize expedited procedures to review a proposed change(s) to previously approved research if it represents a minor change to be implemented during the previously authorized approval period. The IRB defines a minor change to be one that makes no substantial alteration in any of the following:

  1. The probability or magnitude of risks to participants.
  2. The research design or methodology.
  3. The number of participants enrolled in the research.
  4. The qualifications of the research team.
  5. The facilities available to support safe conduct of the research.
  6. The likelihood of participants’ willingness to participate.
  7. Any factor that might warrant convened IRB review.

When reviewing amendments using the expedited procedure, the reviewer will receive and review the same information, outlined above, provided to the  primary reviewer.  The IRB requires that all amendments approved by expedited review are documented and reviewed at the next convened IRB meeting.  If the IRB Chair or expedited reviewer determines that the proposed change to previously approved research represents more than a minor change to be implemented during the previously authorized approval period, the request will be reviewed by the convened IRB.

All amendments that significantly alter the basic design of a study or increase the risk/benefit ratio must be reviewed and approved by a convened IRB.  The amendment should appear as a formal item for discussion on the agenda. The reviewer will receive and conduct an in-depth review of the amendment application (investigator checklist), all modified documents with the changes highlighted, all relevant currently IRB approved documents (approved consent, research plan), the investigator’s written explanation for the changes, and a clean copy of the revised documents.

All other IRB members will have access to and review the amendment application (investigator checklist), all modified documents, and all relevant currently IRB approved documents (approved consent, current protocol) in enough depth to be familiar with them and be prepared to discuss them at the convened IRB meeting.  During the meeting, IRB members may ask the IRB Chair or designee for a copy of the protocol file, meeting minutes, and information provided to the primary reviewers. The IRB Chair will make these items available.

The Convened IRB or IRB Member(s) conducting expedited review may take any of the following actions:

  1. Approval
  2. Approval with Conditions
  3. Deferred for substantive issues

Additionally, the convened IRB may vote to disapprove the proposed changes.  If an IRB member conducting expedited review believes that the proposed modifications should be disapproved, they will refer the amendment to the convened board for review.  If the proposed changes raise significant concerns on the part of the IRB, the IRB may vote to suspend or terminate the research.

The IRB will determine whether re-consenting of currently enrolled participants is necessary.  This determination should be based on new information regarding a change in the risk/benefit ratio that would possibly affect the participant’s decision to continue with the research activities. The IRB will also decide whether participants who have completed the study should be contacted and provided with additional information.

The minutes should reflect the IRBs determinations regarding whether the amendment has changed the risk/benefit ratio of the study and whether the approval period is appropriate to the level of risk.

Approval of an amendment to a protocol does not change the date of the protocol Continuing Review unless the IRB assigns an earlier review date based on the amended information.

When the convened IRB reviews an amendment the discussion, decision and controverted issues (See, CSS IRB SOP #28, Controverted Issues) must be documented just like any other review by the IRB. Likewise, pertinent information and  decisions for an expedited review of amendments must be documented in the IRB records. Proper classification and approval of amendments is as important as the initial and continuing review of research and should be handled appropriately by IRB in the IRB Minutes.

Resources

Case Western Reserve University IRB SOP Amendments

https://case.edu/research/sites/case.edu.research/files/2018-04/CWRU-IRB-SOPs-Amendments.docx

Mayo Clinic - Modification to Previously Approved or Exempt Research

https://www.mayo.edu/research/documents/21-mods-to-approved-researchpdf/doc-10027408

UCLA - Amendments Made to Previously Approved Research

http://ora.research.ucla.edu/OHRPP/Documents/Policy/4/Amendments.pdf

IRB EasyEd. Minor Versus Substantive Amendments. Volume 2 Number 5.  © 2017 Apex Ethical

This is a new policy per the 2018 Common Rule Requirements.

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