Continuing Review

Major Modifications

Major modifications on protocols presenting greater than minimal risk to participants are reviewed and approved by the full Board (e.g., scientific and therapy changes, substantive changes to the informed consent document).

• Documentation regarding major study modifications should be submitted to the Board using Romeo (log-in to Romeo using your username and password), using the same deadlines outlined for initial protocol review.
• Major modifications to clinical drug trials that fall under Division 5 of the Food and Drugs Act require a Health Canada Non-Objection Letter for the amendment. The REB will only approve major modifications of this type after the NOL has been received. Under limited circumstances, the REB can waive the requirement for the Amendment Health Canada Non-Objection letter prior to activation of the protocol modification. The waiver is based on section C.050.008 of the Division 5 Food and Drugs Act, which allows safety-based protocol modifications to be activated immediately providing that the sponsor notifies Health Canada of such changes.

Major modifications to minimal risk protocols (those reviewed under the delegated stream) are reviewed by the Chair only. These are submitted using Romeo.

All modifications should be clearly identified in bold lettering or track changes in the protocol or in an accompanying letter. If changes to the informed consent document are required, these should also be clearly identified in bold lettering or by track changes. Clean copies with version dates, and version numbers on all documents will be required for final approval.  

Minor Modifications

• Reviewed and approved by the Chair
• Minor modifications do not involve significant changes to the design of the project. There are submitted using Romeo. The following are examples of minor modifications that fall under the delegated review process: minor Informed Consent Changes; minor scientific changes (e.g., changes in targeted sample size, accrual objectives, minor changes to inclusion/exclusion criteria). 
• If a minor modification requires changes to the informed consent document, one bolded or tracked changes copy and one clean copy of the modified consent form must be submitted to the Board.

Additional Co-Investigators &/or Research Staff

The addition of a co-investigator and/or research staff that does not modify any study specific documents (i.e., consent forms contact section), does not require submission to the REB office.  Please send an email to [email protected] that indicates the CHEO REB study number, the name of the individual, their role on the study and indicate that there are no changes to study documents.  Please ensure that the additional staff has the appropriate training certificates as well as a ROMEO account; if they do not, the staff will not be added to the study.

Renewals must be filed with the Board yearly. Investigators should use an REB report in Romeo developed for this purpose.

A research project involving human participants will require annual re-approval from the REB as long as the investigator conducting the research continues to collect data about the participants of the research; which includes, entering, collecting and verifying data.

Approval of an annual renewal event form must be obtained prior to the expiry date of approval. A lapse in approval requires that recruitment into the study and all study activities must be discontinued.  Should the investigator wish to continue the research, the study must be re-activated. This requires both a protocol deviation event along with a duly completed annual renewal report.

The Board will force close a study 30 days after the study expiry date. Under these circumstances, a notice will be sent to the investigator and the CHEO Research Institute Administration Office who will suspend access to the study funds.

The date of final approval of a protocol will be determined following the procedures outlined in CHEO REB SOP 408.

The REB follows a procedure for maintaining fixed anniversary dates for the expiration of annual REB approvals. This anniversary date appears on the final approval letter. The final approval letter also specifies the date at which investigators should submit to the Board an annual renewal report. The determination of the expiry (anniversary) dates follows the procedures outlined in the CHEO REB SOP 408.

A research project involving human participants no longer requires annual re-approval when the investigator (1) is no longer collecting data about the participants which includes entering, collecting and verifying data and (2) indicates there is no longer a need to obtain more data for the research project.  

A study is normally conducted in compliance with the most recent version of the protocol, which has been previously approved by the REB. At times, study procedures can deviate from the approved protocol. The investigator can implement a protocol deviation without the approval of the REB when necessary to eliminate an immediate risk or hazard to the research participant. As soon as possible, however, after the implemented deviation or change, this form and, if appropriate, the proposed protocol amendment(s) should be submitted to the Board for review in Romeo.
Protocol deviations  may impact the participant’s rights, safety or welfare, or that can affect the integrity of the study data; as such should be reported to the REB using in Romeo. Please note that the following are examples of deviations, however, not limited to those listed below: 

Examples:

• Failure to obtain informed consent;
• Enrolment of a patient not meeting inclusion criteria;
• Failure to report a serious adverse event;
• Study medication dispensing or dosing error;
• Study procedure omitted;
• Failure to file REB Annual Renewal and/or Modifications
• Study procedures conducted out of sequence, but with no impact on participant safety or welfare;
• The use of the same recruitment materials in a new venue (community vs. local newspaper). 

Investigators must promptly report to the REB all adverse events that are both serious and unexpected, and any new information regarding the safety of research participants that becomes available during the course of the study. Based on international guidance documents, the following circumstances constitute SAEs: congenital anomalies, significant disability or incapacity, prolonged hospitalization, and any other life-threatening or medically-important events. Occasionally, changes to the study documentation are required as a result of these events.

The Chair and the Director of Pharmacy regularly review the SAE reports. These SAEs are also presented to the REB members for their review. A signed copy of the report will be returned to the Research Assistant/Coordinator or Primary CHEO Site Investigator. Submit an original plus one copy of the Serious Adverse Events form (with appropriate documentation). Reports prepared by the Study Sponsor are also accepted by the Board.

The investigator must verify the dose and administration of all study medications associated with SAEs having occurred at CHEO.  See Policy with respect to considering Medication Error in the Differential Diagnosis of Severe Adverse Events (SAE).

The REB must be advised of all study closures (to accrual permanently or temporarily, and permanently closed).  A study closure report should be submitted in ROMEO.

Study Closed to Accrual

The REB must be advised if a study closes to accrual permanently or if accrual is temporarily suspended.  A change in study status report should be submitted in ROMEO. 

Permanent Study Closure

A study should be permanently closed, if:

• The study was never initiated and there are no plans to do so in the future.
• The research project is no longer collecting data about research participants, which includes entering, collecting and verifying data, and there is no longer a need to obtain more data for the research project.
• The study is interrupted unexpectedly (e.g., the sponsor withdraws support, the investigational agent is no longer available, etc.).

 A study closure report should be submitted in ROMEO.