Submission and Review Procedures for Amendment /Changes to the Previously Approved Study

1.0Introduction

Researchers are obliged to follow the procedures outlined in the protocol/proposal approved by the Research Ethics Board (REB). If the researcher or sponsor recognizes the need for modification to the protocol/proposal he/she is obliged to file a protocol amendment with the REB prior to implementing the change.

The following guideline outlines:

the necessary information that is required of the applicant when submitting a request to the REB;and

details the operating procedures of the Bannatyne Campus REBs review process related to amendments.

3.0Review Procedures

There are three levels of review conducted by the REB when changes to the protocol are made:expedited review, full board review and administrative review.

3.1 Expedited Review

In most cases, the REB Chair will review and, if appropriate, approve an amendment that involves minor changes or changes that are of minimal risk to participants on behalf of the board, provided it is not required by the sponsor to submit the amendment for full board review. The Chair may decide, however, that some major protocol amendments need to be reviewed by the board at the monthly REB meetings or that a particular amendment requires review by a subcommittee of board members prior to implementing the changes. Accordingly, applicants should anticipate the possibility of a full review in the timing of their submission.

In addition and prior to the initial review by the Chair, the REB coordinator reviews/screens all requests for approval of the amendment to ensure compliance with local policies and regulations. The REB coordinator will contact the Principal Investigator (PI) or delegate with recommended suggestions when the amendment and or supporting document(s) clearly do not comply with the policies of the board.

3.1.1 Timelines

Amendments are usually reviewed on a weekly basis by the Chair. The time of submission of an amendment to review will vary according to the volume of submitted amendments and new applications. The approval period is usually within 10 business days provided no clarifications or revisions are requested by the Chair or REB coordinator.

3.1.2 Decisions

Certificates of approval for approved amendments are mailed usually within one business day from the decision of the chair. This certificate is forwarded either tothe Principal Investigator or the individual requesting the information on the submission.

If minor changes are requested the REB coordinator will contact the PI/study coordinator by e-mail or phone. When major changes are requested or the amendment is not approved, the chair will specify the conditions required to grant approval in writing to the PI.

3.1.3 Approval Period of Amendment

The term of approval for the amendment expires at the same time as the initial approval/annual approval renewal for the study. Annual approval implies that the most recent versions of the protocol/amendment and supporting documents are approved. This applies to amendments reviewed by the full board or expedited by the chair.

3.2Full Board Review

3.2.1 Sponsors that require Full Board Review

Some sponsors require full Board review for amendments. Studies funded by the United States Department of Health and Human Services (DHHS)(i.e. NIH, Center for Disease Control) or studies sponsored by other United States Federal Agencies may require full board review. The researcher must familiarize themselves with the requirements of the sponsor to ensure the appropriate review is received.

3.2.2 Amendments Requiring Full Board Review

Major amendments to the study design, inclusion/exclusion criteria or study interventions which involve additional risk(s) tostudy participants generally, will require review at the monthly full board meeting. The Chair will make the final decision as to whether full board review is required.

Examples of amendments, which should be reviewed by the full board, are listed below:

  • An amendment which adds an open label phase to a randomized clinical drug trial
  • Genetic sub-study or collection of blood for genetic analysis
  • Inclusion of children or vulnerable population as a new study group
  • Inclusion of normal healthy volunteers as a new study group in a clinical trial
  • Additional study procedures above minimal risk e.g. bone biopsy, colonoscopy, etc.
  • Any major change in inclusion/exclusion criteria which may affect subject safety
  • Major change in study design i.e. adding new treatment arm to clinical drug/devise trial
  • Revisions to survey and/or interview questions that include unduly, alarming, intrusive, sensitive or potentially embarrassing themes.
  • Any major amendment, judged by the REB Chair as requiring full board review.

3.3Administrative Review and Changes which may not require written approval

The following administrative changes will not receive written approval or written acknowledgement by the REB. The study site must maintain a record of their correspondence to the REB as documentation of the submission. These changes are reviewed on behalf of the committee by the REB coordinator and recorded in the appendices distributed to the REB.

  • Administrative letters which outline administrative aspects of the study (i.e. changes in sponsor personnel; telephone number and addresses changes; formatting or typing errors and other minor clarifications of study documents) or Standard Operating Procedures of the sponsor.A change in sponsor is not regarded as a minor administrative aspect and therefore requires approval by the REB or REB Chair.
  • Changes in local study personal other than the Principal Investigator. Administrative changes such as a change in study nurse or telephone number can be made to the Informed Consent Form without prior written approval. Subsequently, a letter should be submitted to the REB notifying the office of the change with the revised informed consent form(ICF) included. In these cases, the version date of the ICF should not be revised, as there is no change in the actual content of the document. Should the sponsor require a new version date for such administrative changes, the letter to the office must indicate that approval is required by the sponsor for the new version. Note: written approval is required when the ICF is revised to include a new sponsor or PI.

4.0 Changes that can be implemented prior to written approval.

An appropriate amendment may be implemented without prior written approval, when in the Investigator’s opinion the amendment is necessary to eliminate immediate hazards to the subjects or when the change involves only logisticor administrative aspects of the trial. If time permits it is suggested that the Investigator contact the REB office for guidance on such matters prior to implementing the changes. At the earliest possible convience the Investigator must notify the REB with a summary of the actions taken and indicate when a formal amendment summary is expected.

5.0 Submission Process

Expedited Review:

When expedited review is appropriate submit one copy of the following applicable documents to P 126 -770 Bannatyne Avenue:

Request for Amendment Form(required for all amendments)

Amendment summary -with changes/additions clearly markedand new version date

Revised Protocol– new version date on document.

Informed Consent(s) - with changes/additions clearly markedand new version date inserted in footer of each page.

Supporting documents such as advertisements, questionnaires, etc - with changes/additions clearly markedand new version date inserted in footer of each page

Health Canada“No Objection Letter” (NOL)or rationale from the sponsor why Health Canada approval is not required( if applicable)

Additional copies may be requested of the investigator’s site if it is determined by the Chair or REB coordinator that full board review is required.

Full Board Review:

Hand deliver or courierto P 126 -770 Bannatyne Avenueby the full board submission deadline date.

15/20 copies(HREB/BREB) of the following applicable documents:

Amendment Form(required for all amendments)

Informed Consent(s) - with changes/additions clearly markedand new version date inserted in footer of each page.

5 copies of the following documents:

Amendment summary -with changes/additions clearly markedand new version date added to document.

Revised Protocol – new version date on document.

Supporting documents such as advertisement, questionnaires, etc - with changes/additions clearly markedand new version date inserted in footer of each page.

Health Canada No Objection Letter (NOL) or rationale from the sponsor why Health Canada approval is not required( if applicable)

5.1What to include in required documents:

  1. Cover Letter:

A cover letter is generally not required and is only suggested if the request is not detailed in the Bannatyne Campus Amendment Form of if you are submitting a request for minor changes to the recruitment plan, advertisements and minor changes to patient information material.

If you are submitting a cover letter, the letter must list the documents (include protocol number and version dates)submitted for review and specify whether full board or expedited review is requested. In the case of expedited review, the PI must indicate whether expedited review is acceptable to the sponsor for the proposed amendment/change to the study and justify that the changes pose no additional risk to participants.

  1. Bannatyne Campus Research Ethics Board Request for Amendment Form:

This form must be completedwhen there are any changesmade to the protocolwith the exception of the following: minor changes to the recruitment plan,requests for approval of advertisements and minor changes to patient information materialsother than the Informed Consent forms. In these cases a cover letter detailing the request can be submitted.

This form must list the documents (include protocol number and version dates) submitted for review and specify whether full board or expedited review is requested. In the case of expedited review, the PI must indicate whether expedited review is acceptable to the sponsor for the proposed amendment/change to the study and justify that the changes are minor and pose no additional risk to participants.

For both full Board and Expedited Review, the REB reviewers require a list and summary of the nature of any previous amendment(s) so that it is easy to track how the study has been amended overtime. The summary should include only those amendments that had been submitted either after the initial approval or subsequent annual renewal.

This form must include a brief overall summary and rational of the major changes, which provides the reviewer with an understanding of the major intent of the amendment.

  1. Protocol Amendments:

This document must include a brief overall summary and rational of the major changes, which provides the reviewer with an understanding of the major intent of the amendment. If this information is not included in the amendment summary, it must be provided on the Bannatyne Campus Research Ethics request for amendment form. In addition, the document must be submitted in such a way that the changes can be clearly identified (i.e. additions bolded or underlined and deletions indicated by strikethrough) and rational provided for each change. If not included in the document provided by a sponsor-initiated trial, the PI must submit an amendment summary/letter that details the changes and rational or include this information on the amendment form.

In the case of a protocol amendment generated by the sponsor, the PI must provide a copy of the signed Investigator agreement page.

  1. Consent Form(s):

Submit the amended consent form, with additions underlined or in bold text and any deletions indicated by strikethrough. This makes it easy for the reviewers to see how the amended consent form was revised. The amended consent form must include an updated version date in the footer or header of each page. The REB office may return the amended consentform to the PI if the changes are not highlighted as indicated above.

One copy of the clean version of the ICF should be included for the REB file.

  1. New Documents/Revised Documents:

Submit any new or revised questionnaires, diaries, recruitment letters, etc. As indicated above, any changes should be clearly highlighted and bolded for ease of review in revised documents. The amended documents must include an updated version date.

  1. Supporting Documents:

If appropriate, submit letters of support from interest groups, school boards or Treaty Band approval, etc.

  1. Health Canada No Objection Letter:

If a “No Objection Letter” (NOL) from Health Canada (HC) was received for the initiation of the clinical trial, then a copy of the”NOL” from HC for the proposed changes to the protocol must be provided before the REB will approve the proposed amendment or an appropriate justification from the sponsor outlining why the amendment was not submitted to HC for review is required.

University of Manitoba Bannatyne Campus REBPage 1 of 5

Submission and Review Procedures for Amendment /Changes to the Study

Version Date January 20, 2007