Ongoing Maintenance of your Protocol
Post-Approval/Reportable Event Forms Available on WREM
All post-approval (any submission completed following initial approval of a research study) forms are available on, and must be submitted via, WREM. The Office of Human Research Ethics will not accept online submissions (initial and post-approval forms) unless:
- They are submitted by the PI; and
- All relevant documents are included (if applicable).
The submission will not be accepted for review if these conditions are not met. These guidelines are in conformity with requirements for continuing ethical review as set out in the Tri-Council Policy Statement, and in compliance with regulations governing clinical trials (Health Canada regulations for the investigational use of drugs, radiopharmaceuticals, biologics, natural health products and medical devices), ICH GCP E6, and where relevant, the U.S. Code of Federal Regulations.
- Changes in Study Personnel
- Letter of Attestation
- Unanticipated Problem Reporting
- Continuing Ethics Review (CER) Form
- Amendment Form (Previously “Revision Form”)
- Acknowledgement Request Form (FYI Form)
- Data Safety Monitoring Committee Form
- Updated Approval Form
- End of Study Form
- Protocol Deviation/Violation Form
A formal approval letter will only be issued for the following post approval submissions:
- Amendment Forms
- Updated Approval Forms
- Continuing Ethics Review (CER) Forms
An Acknowledgment of Receipt email will be issued for the following submissions:
- Change in Study Personnel (other than PI and CoI)
- Acknowledgement Request Form (FYI Form)
- Data Safety Monitoring Committee Form
- End-of-Study Report Form
Letter of Attestation
Any post-approval form that is not submitted directly by the PI requires a separate Letter of Attestation if not being submitted within the WREM system. A Letter of Attestation is completed by the PI authorizing the submission. An Attestation Letter must be included as an attachment. All Letters of Attestation must include the following information:
- HSREB/NMREB file number
- Study Title
- PI Name
- Name of post-approval form being accompanied with the attestation letter
- Statement of acknowledgment from the PI authorizing the post-approval submission (ensure to state what type of submission it is)
- PI signature
Note: All submissions within the WREM system require PI sign off
Study Personnel Amendments
Changes to PI and Co-I require submission of an Amendment 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
Changes in study personnel (non-PI/Co-I) will need to be completed by the Project Owner within the WREM system. This can be done by adding the individual into the Roles tile within the specific study. This individual will need to have an active WREM account to be added to the study. Please note this does not list them in the protocol but will give them access to this study which you can customize within the Collaborators tab.
You do not need to submit an amendment for the addition of research staff however, in the next amendment that is submitted to the OHRE please ensure the personnel listed in the protocol is up to date.
If you require further instructions plesase 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).
When your study has ended you are required to submit an End-of-Study Form.
The office of Human Research Ethics will NOT accept CER Forms unless they are submitted by the PI, or have an accompanying Letter of Attestation authorizing this submission. If a Letter of Attestation is used, please see the ‘Letter of Attestation’ section above for more details, including Attestation Letter requirements)
To help facilitate compliance, the office will issue reminder notifications for when CER forms are due. This will occur two months and one month before the due date. If a CER form is not submitted by the due date the office will send a third and final notification just before your study will expire. Should an Investigator fail to submit the CER form despite the reminder/follow-up notifications, a notice that REB approval has expired will be issued and the study will be suspended. When suspended, the Investigator must suspend all study related activities as specified by the REB. If the CER form is still not submitted within two weeks of the study expiry date the REB may close the file and the Investigator will be required to submit a new study application. If the CER form is submitted after the expiry date, but before file closure, this will result in a lapse in REB approval. The REB may also elect to pursue investigations for serious or continuing non-compliance.
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.
All changes to the planning or conduct of approved studies are considered amendments and must be submitted to the relevant ethics board for prior review and approval to ensure the research remains ethically sound. The Principal Investigator (PI) must ensure that amendments are submitted to the board for review and that written approval is received prior to implementation.
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 Full Board review may be required when the proposed change(s) represents more than minimal risk and is determined by the HSREB 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 significantly affect the conduct of the research or increasing 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.
Health Canada “No Objection” letters (NOLs) or equivalent must be included with Amendment submissions for regulated clinical trials when applicable. When applicable, 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 PI (and study staff listed in ROMEO as “research support staff) in writing. 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.
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 Office of 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 Office of Research Ethics 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 not be accepted for reviewed.
Required Documentation (in addition to Amendment Form)
- Separate summary of the changes page detailing what is being changed and why (if available)
- Revised Application Form (see below for instructions)
- 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/mmm/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). If changes are required for the Application Form (also considered the “Western Protocol”):
- 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. Save in PDF format. This is your “Clean” copy;
- Attach the Tracked and Clean copies to the submission. PLEASE ENSURE TO INCLUDE A VERSION DATE (e.g., dd/mmm/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.
Unanticipated Problem Reporting
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))."
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 ROMEO.
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 University’s REBs 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.
DO NOT use this form if what you are submitting is making any changes to the approved Application Form (also considered the “Western Protocol”) 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 should not be submitted. Only if the updated safety information requires a change to the Letter(s) of Information/Consent and/or protocol, should it be submitted to the office of Human Research Ethics as an Amendment.
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.
- Copy of the Data Safety Monitoring Committee findings/report to the DSMC Form
The office of Human Research Ethics will NOT accept this submission unless: (1) it is submitted by the PI or have an accompanying Attestation Letter authorizing this submission. If a Letter of Attestation is used, please see the ‘Attestation Form’ section above for more details, including Attestation Letter requirements); and (2) all relevant documents are included (if applicable). If (1) or (2) are missing, the submission will not be accepted for review.