Review of Modifications to Previously Approved Research- PRO148   

Modification means proposed changes in the conduct of the study that may affect the protection of human subjects. A minor modification is a modification that involves no more than minimal risk and which all added procedures fall into categories one through seven of the categories of research allowing review using the expedited procedure. (See PRO150 Procedure for Continuing Review of Research by the Expedited Procedure.) Minor modifications proposed for previously approved research may be reviewed in an expedited procedure by the IRB in accordance with 45 CFR 46.110 and 21 CFR 56.110. When a proposed change in a research study is not minor, the IRB must review and approve changes at a convened meeting before the change can be implemented. The only exception is when a change is necessary to eliminate apparent immediate hazards to the research subjects. Problems or new information that may affect the risk-benefit assessment must be promptly reported to, and reviewed by, the IRB to ensure adequate protection of human subjects per POL006 UAB Policy to Ensure Prompt Reporting of Unanticipated Problems Involving Risks to Subjects or Others to the IRB and PRO106 Procedure To Ensure Prompt Reporting Of Unanticipated Problems Involving Risks to Subjects or Others.

Procedure
 

Investigator’s Responsibilities

Investigator:

• Refrains from initiating modifications (changes to the research) without IRB review and approval of those modifications in approved research during a period for which IRB approval has been given, except when necessary to eliminate apparent immediate hazards to the subjects;
• Submits FOR200 IRB application eForm with the amendment request section completed for approval of proposed modifications (changes) in the approved research and any proposed plans to re-consent previously enrolled subjects;
• Submits with amendment request all modified documents related to the modification (e.g., informed consent document(s), recruitment material, or advertisements, and PORF if DoD sponsored study;
• Submits additional information related to applicable special populations by completing the appropriate section(s) of the IRB application eForm when a modification affects participants from populations protected under subparts B, C, or D;
• Reports modifications (changes) taken prior to IRB approval to eliminate an apparent immediate hazard to subjects by completing the amendment section of the IRB application eForm and submitting it within 5 working days of initiating the change.

OIRB Responsibilities

Administrative Staff:

• Routes all amendment submissions to a reviewing staff member;
• Distributes amendment materials to IRB in accordance with (see PRO145 Procedure for Timing of Document Distribution for IRB Meetings);
• Prepares a list of protocol amendments approved through the expedited procedure for convened IRB confirmation.
• For modifications referred to the convened IRB:
  • Drafts letter of IRB action to principal investigator for review by management staff and/or Chair;
  • Assures entry of protocols scheduled for IRB review into electronic research administration system;
  • Enters final actions into the electronic research administration system;
  • Once final approval is issued, enters date issued into electronic system and sends the approval form and stamped approved informed consent document(s);
  • Includes information in the draft minutes of the IRB meeting for review by the management staff.

Reviewing Staff:

• For all modifications:
  • Reviews all amendment submission materials for completeness;
  • Requests additional information from research team, as needed;
  • Reviews modification for effect on data safety monitoring plan;
  • Marks minor modifications in amendment and all modified document(s) for review by the IRB Chair (or designee);
  • Forwards amendment submission materials to either the IRB Chair (or designee) for review and either approval or referral to the convened IRB.
• For modifications referred to the convened IRB:
  • Refers submissions for entry into electronic research administration system;
  • Reviews modifications prior to meeting;
  • Takes notes on IRB actions for each protocol during convened meeting along with technical writer;
  • Reviews a draft of the letter being issued on behalf of the IRB to the principal investigator.

IRB Responsibilities

The Chair or designee:

• Reviews the proposal and verifies that the modifications to the research represent minor modifications.
• Reviews all modified documents;
• Uses GUI329 Criteria for Approval Tool to determine whether the research meets the criteria at 45 CFR 46.111, and Subpart D if applicable, and 21 CFR 56.111 if applicable, and 21 CFR 56 Subpart D if applicable.
• Reviews and determines if the requirements of PRO125, if applicable, are satisfied; in addition to 46 CFR 46 Subparts B and D, if applicable, and 21 CFR 56 Subpart D, if applicable for minor modifications related to vulnerable populations.
• Approves the research study or approves research following modifications to receive approval, if the below criteria are satisfied and returns to reviewing staff memeber to review approval status.
• Refers the protocols that cannot be reviewed by the above procedure to management staff to schedule for convened IRB review.
• Reviews and may approve proposed modifications that are:
  • Minor modifications—modifications that involve no more than minimal risk and in which all added procedures fall into categories one through seven of the categories of research allowing review using the expedited procedure;
  • Reduce the risks/discomforts to the subject;
  • Study staff changes (e.g., subinvestigators or research nurses);
  • Advertisements of previously approved research.
• Refers all modifications not approved under criteria above to the next available convened IRB meeting.

Each Primary IRB reviewer:

• Receives and reviews in depth all of the following assigned materials for amendment submissions for presentation at convened IRB meeting:
  • IRB application eForm with amendment request section;
  • Revised informed consent document(s), if applicable;
  • Revised sponsor’s protocol;
  • Revised Investigator’s Brochure or package insert, if applicable;
  • Recruitment materials, advertisements, or questionnaires, if applicable;
  • Change in protocol status.

The IRB:

• Takes action on all amendment submission materials referred by the Chair in accordance with 45 CFR §§46.103, 46.109, 46.111, and 46.116; with 21 CFR §§56.103, 56.109, 56.111, and 56.116, and any other funding agency, as applicable;
• Review and makes a determination whether the requirements of PRO125, if applicable are satisfied; in addition to 45 CFR 46 Subparts B, C, and D, if applicable, and 21 CFR 56 Subpart D, if applicable when the research involves vulnerable populations;
• Decides whether the modifications require the investigators to provide information relating to protocol changes that may affect a participant’s willingness to continue to take part in the research;
• Reviews and makes a determination on modifications for change in the data safety monitoring plan;
• Takes action and assigns one of the following classifications to the modification:
  • Approved—No modifications required. Research activity meets 45 CFR 46.111 or 21 CFR 56.111;
  • Additional Information Required—May be used when there are specific modifications required by the IRB to be reviewed by one experienced IRB member by the expedited procedure before formal approval can be issued. Cannot be used for modifications or clarifications that are related to the regulatory criteria for approval;
  • Deferred for Response—IRB requested clarification to the human subjects protocol. The response to the IRB and/or informed consent document will be reviewed at a convened meeting of the IRB before formal approval can be issued;
  • Disapproved—The research did not meet 45 CFR 46.111 or 21 CFR 56.111;
  • Sponsor-Imposed Interruption—The IRB receives written notification from the investigator that the sponsor has interrupted the research study. This will be acknowledged by the IRB Committee, Chair or his/her Designee when the appropriate level of review determines the interruption is appropriate. The IRB may take additional action, if needed, to protect the participants from potential harm. This determination may be made for interim data analysis, inadequate drug availability, in response to a DSMB report/recommendation, or a planned stopping point;
  • Suspension of IRB Approval—IRB made a determination to temporarily suspend or withdraw approval of all or some specific research activities indicating that the specified activities must cease immediately. The only exception will be for the continuation of IRB approved follow-up activities necessary to protect the participants’ safety.
  • Termination of IRB Approval—The IRB made a determination to permanently withdraw approval of all research activities, indicating that the specified activities must stop immediately. The only exception will be for the continuation of IRB approved follow-up activities necessary to protect the participants’ safety.
• Provides written communication to the principal investigator of IRB action within 10 working days. If a protocol is deferred or disapproved for any reason, the committee includes reasons for the action and an invitation to respond to the IRB in writing or in person. Any suspension or termination of IRB approval or sponsor-imposed suspension will be processed according to POL038 UAB Policy on Suspension or Termination of IRB-Approved Research and Administrative Hold and PRO140 Procedure for Suspension or Termination of IRB-Approved Research and Administrative Hold.