Post-Approval Events

All changes to the planning or conduct of approved studies are considered amendments and must be submitted to the relevant ethics board for review and approval to ensure the research remains ethically sound. The Principal Investigator (PI) must ensure amendments are submitted to the board for review and that written approval is received prior to implementation.

Amendment Review Process

The HSREB/NMREB Chair or designee reviews the Amendment submission to determine the appropriate level of HSREB/NMREB review required. Delegated review may be done when the proposed changes are minor or involve no more than minimal risk. The REB Chair or designee has the authority to direct any delegated review request to the Full Board for review.

HSREB/NMREB Full Board review may be required when the proposed change(s) represents more than minimal risk and is determined by the HSREB/NMREB Chair to require more intense scrutiny by the Full REB, or is required by the regulatory body. Examples that may require full board review may include:

• Proposed changes to the (scientific) intent of the research;
• Reports of any changes that significantly affect the conduct of the research or increase the risk to research participants; and/or
• New information that may adversely affect the safety of the research participants or the conduct of the research.

Amendments that qualify for Full Board review are generally reviewed at the next HSREB Full Board meeting. You will be informed if your Amendment submission requires Full Board review.

When applicable, Health Canada “No Objection” letters (NOLs) or equivalent must be included with Amendment submissions for regulated clinical trials. REB approval for an Amendment will not be granted until the NOL or equivalent Health Canada authorization (ITA, NOA, etc.) is received.

Following the Amendment review, REB recommendations regarding Amendment submissions are communicated to the study team via the WREM system. The PI will have an opportunity to submit additional information and/or a revised study documents that addresses any issues raised in the HSREB review.

Sub-Studies

The HSREB generally does not consider sub-studies, ancillary studies, rollover studies, continuation studies, or extension studies to be Amendments. You are encouraged to consult the Research Ethics Officer responsible for your study prior to preparing a submission for this type of change, to ensure you prepare the correct type of submission. The Ethics Officer will facilitate obtaining a decision from the HSREB Chair/Co-Chair.

The human research ethics team will NOT accept this submission unless:

• It is submitted by the PI.
• All relevant documents are included (if applicable).  If either is missing, the submission will be returned as incomplete to the study team.

Required Documentation (in addition to Amendment Form)

• Separate summary of the changes page detailing what is being changed and why (if available)
• Revised Protocol/Research plan
• New or revised Letter(s) of Information & Consent
• Other study related documents that require changes

Revised Study Document Requirements

All revised study documents must have version dates (e.g., dd/mm/yyyy) in the footer of each page. Version dates identify the latest edition of study documents. A new version date is required each time the document is modified. For example, if a study document requires further modification based on comments received during the REB review process, the version date must be modified to reflect the most recent edition of that study document.

Please also ensure to submit one copy with tracked changes and a clean copy of all revised study document(s), as follows:

• In Microsoft Word: make changes (including version date) to the document using the ‘track changes’ function. This is your “Tracked” copy;
• Save Tracked copy in Word format. Duplicate the Tracked copy and accept all changes. This is your “Clean” copy;
• Attach the Tracked and Clean copies to the submission. PLEASE ENSURE TO INCLUDE A VERSION DATE (e.g., dd/mm/yyyy) in the footer of all study documents; and
• Every time an amendment is made to this document, please remember to revise the version date to reflect the changes made and re-submit the entire document.

Study Personnel Amendments

Change in Principal Investigator (PI) and Co-Investigator (Co-I)

Changes to PI and Co-I require submission of an Amendment sub-form in WREM. The following documentation is required:

• HSREB/NMREB Amendment Form 
• Tracked and Clean copies of any previously approved study documents affected by the change in PI/Co-I

Change in study personnel other than the PI and Co-I

Changes in study personnel (non-PI/Co-I) require submission of an Amendment sub-form in WREM. New study personnel will need to have an active WREM account. The following documentation is required:

• HSREB/NMREB Amendment Form 
• Tracked and Clean copies of any previously approved study documents affected by the change in study personnel

In order for new study team members to access the file, ensure they are updated within the actual WREM system. This can be done by adding the individual into the Roles tile within the specific study. This will give them access to this study which you can customize within the Collaborators tab.

For studies previously approved in the Romeo system you will need to submit an amendment to add or remove study personnel. This amendment requires that the last approved Western Protocol from Romeo be updated. 

Note: If the number of study team members exceed the number of allocated spots in Q1.4 of the WREM initial application OR Q1.7 of the amendment form then a separate document must be submitted listing all study team members. This document must include:

1. All individuals who are a part of the study, including those already listed in Q1.4 or Q1.7.
2. The study team members’ email address.
3. The study team members’ role.
4. The study team members’ duties.
5. The study team members’ faculty/department.

 This study team member document must be included for all Amendments with changes to study team personnel. 

If this study was previously approved in Romeo (or prior to) the previously approved Western Protocol must be updated with all the required information as indicated above.

If you require further instructions please see the WREM Training Materials on our WesternREM Information page or within the WREM system (Help button on top navigation bar then select Help from the drop down menu).  

Western’s HSREB/NMREB approves studies on an annual basis. If your study is ongoing for more than one year, the office will issue an Annual Renewal Approval Notice for one year at a time upon the submission and review of a CER form. Depending on risk, continuing review may be required more than once per year; you will be informed if this is the case.

When your study has ended you are required to submit a Study Closure Form.

The HSREB/NMREB will NOT accept CER Forms unless they are initially signed and submitted by the PI. If recommendations are received, a delegate on the study team can re-submit the form to our office for review on the PI's behalf.

To help facilitate compliance, the WREM system will issue automatic courtesy reminder notifications when CER forms are due. This will occur 45 days, 30 days and 7 days before the study expiry date. Should an Investigator fail to submit the CER form despite the reminder notifications, a notice that REB approval has expired will be issued and the study will be suspended. If suspended, the Investigator must suspend all study related activities as specified by the REB.

Please note, once a project expires with the REB, the PI’s name will be placed on a Holds List where the office will not accept new projects or forms for review until all outstanding projects are in good standing. If the CER form is still not submitted within two weeks of the study expiry date the REB can assign the project to the next available board meeting for the board to vote to close this project. If the study team would like to continue the project, a CER form will need to be submitted and will be processed at the next applicable Full Board meeting to determine if the project can be re-opened. If the study team would like to close the study, then submission of a study closure form will be required. Once either the CER has been approved or the study closure has been acknowledged the PI will be removed from the Holds list.

Initiating or continuing the conduct of human participant research in the absence of REB approval does not conform to the Tri-Council Policy Statement 2 (TCPS 2) and for regulated studies, is contrary to Health Canada, FDA and OHRP regulations. The HSREB/NMREB may also elect to pursue investigations for serious or continuing non-compliance

Protocol Deviations/Violation Form

Please see the Unanticipated Problem Reporting-Protocol Deviation (PD) guideline document to determine which PDs require reporting to the REB. If the submission does not meet the reporting requirements for events, the submission will be withdrawn. Please submit your report in WREM.

Definition of Protocol Deviation

The term protocol deviation is not well defined by regulations or guidelines. Deviations are identified as any unanticipated or unintentional divergence or departure from the expected conduct of an approved study that is not consistent with the approved Research Ethics Board (REB protocol or protocol procedures). Deviations are different from amendments in that they generally apply to a single occurrence or participant and are not intended at the time to modify the entire protocol. Protocol Deviations are unanticipated issues and they include unauthorized collection, use or disclosure of personal health information that is not in compliance with the approved study protocol, jurisdictional legislation or its regulation.

ICH GCP Requirements

a) Article 4.5.4 of the ICH-GCP:

"The investigator may implement a deviation from, or a change of, the protocol to eliminate an immediate hazard(s) to trial subjects without prior IRB/IEC approval/favourable opinion. As soon as possible, the implemented deviation or change, the reasons for it, and, if appropriate, the proposed protocol amendment(s) should be submitted:

• To the IRB/IEC for review and approval/favourable opinion
• To the sponsor for agreement and, if required,
• To the regulatory authority(ies)."

b) Article 4.5.4 of the ICH-GCP:

"The investigator should not implement any deviation from, or changes of the protocol without agreement by the sponsor and prior review and documented approval/favourable opinion from the IRB/IEC of an amendment, except where necessary to eliminate an immediate hazard(s) to trial subjects or when the change(s) involves only logistical or administrative aspects of the trial (e.g., change in monitor(s), change of telephone number(s))."

Adverse Event Reporting

Please see the Unanticipated Problem Reporting - Adverse Events guideline document to determine which Serious Adverse Events (SAEs) require reporting to the REB. If the submission does not meet the reporting requirements for events that constitute Unanticipated Problem, the submission will be withdrawn. Please submit your report in WREM.

Local Serious Adverse Events:

Only those local (internal) serious adverse events that meet the definition of an unanticipated problem (i.e., unexpected, related and involving greater risk – see guidance document) are required to be reported to the REB. Local serious adverse events that meet the definition of an unanticipated problem should be reported to the REB promptly, but in any case no later than seven (7) days subsequent to the occurrence of the local event.

Non-Local Serious Adverse Events:

Western’s HSREB/NMREB will ONLY accept individual case reports of non-local (external) SAE's if they are unanticipated problems (see guidance document).  In the limited circumstances where an Individual Non-Local (external) SAE constitutes an unanticipated problem the report should be submitted to the REB as soon as reasonably possible, but in any event, no later than within seven (7) days after the Investigator has received the report from the sponsor.

FYI Form (Acknowledgement Request Form)

DO NOT use this form if what you are submitting is making any changes to the approved Application Form (also considered the protocol/research plan) or any supporting documentation.

Updated Investigator Product Documentation

Updated Investigational Product Documentation (e.g., Investigator Brochures, Product Monographs, Device Manuals, etc.) that do not alter the benefit:risk assessment of the study can be submitted as an FYI. If the updated safety information requires a change to the Letter(s) of Information/Consent and/or protocol/research plan, should it be submitted to the office of Human Research Ethics as an Amendment.

Data Safety Monitoring Committee report

Per article 11.7 (TCPS2) A safety monitoring plan may (but need not) include the establishment of a data safety monitoring board (DSMB) or data safety committee (DSC).

A DSMB is normally a multidisciplinary, expert advisory group that is responsible for safeguarding the interests of participants, by reviewing emerging data, assessing the safety and efficacy of trial procedures, and monitoring the overall conduct of a trial. Researchers must indicate, in their proposal for REB review, whether they or a DSMB will be communicating any new information to the REB over the course of the trial. Researchers must ensure that DSMB reports are sent to REBs in a timely manner.

Required Documentation (in addition to the DSMC Form)

• Copy of the Data Safety Monitoring Committee findings/report to the DSMC Form

Submit when a study is completed (no further participant involvement, data collection, chart access, data clarification & data transfer).

The office of human research ethics team will NOT accept this submission unless: it is submitted by the PI and all relevant documents are included (if applicable). If either requirements are missing, the submission will not be accepted for review. Once the file has been closed no sub-forms will be accepted for review and approval/acknowledgement unless the study team re-opens the file. If the study team would like to re-open a project with the HSREB/NMREB please contact the office and they will instruct you on the re-opening process. Note, depending on the length of time the project has been closed some projects may require a new application.