REB Approval is only one element of Institutional Approval (required to begin a study at UHN).
REB receives the study.
REB triage the incoming study based on several factors including risk.
Review assessment is conducted.
A decision to approve the study is made.
Modifications are requested.
More information is required.
When submitting a study, the REB determines one of the following review paths, depending on the nature and risk profile of the submission. This application is only completed once per study.
CAPCR is an online tool that manages the electronic submission process for clinical research studies by streamlining the approval process. CAPCR compiles and coordinates approvals from different departments (including REB) and allows you to track your progress towards achieving Institutional Approval. To learn more about the CAPCR application, click here . UHN's CAPCR can be accessed internally from the research network, or externally through the Remote login page. *For issues accessing the CAPCR application, please contact the CAPCR team directly.
Is the research study open to accrual/enrolment? | ||||
Renew via CAPCR | Is the research study closed to enrolment but subjects are still participating in research procedures outlined in the protocol? | Close via CAPCR | ||
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Is data clarification, access to patient charts and/or data transfer ongoing? |
For more more information on unanticipated event reporting at UHN, please consult the following PDF document (requires Adobe Acrobat Reader): Unanticipated Problem Reporting Guidance . To report an unanticipated event at UHN, please do so via CAPCR.
All research involving humans or confidential patient information within UHN requires approval of the UHN REB prior to the initiation of a research project.
Investigators from other institutions who wish to carry out research on UHN premises or with UHN patients or patient data must also apply to the UHN REB.
The definition of research is outlined in the Tri-Council Policy Statement . In summary, research involving humans is considered to include any of the following:
If you cannot determine whether an intended investigation constitutes research, contact the Chair of the REB or an Ethics Coordinator for assistance.
In accordance with the Tri-Council Policy Statement , the UHN REB conducts a proportionate review of research protocols: that is, the scale of the review is in accordance with the type of research proposed and with the potential for harm that the research may pose
The decision to delegate a research project is made by the Co-Chairs of the REB. Some criteria by which research may qualify for delegated review are:
The REB is comprised of four panels. The panel to which proposals are directed for review depends on:
Decisions as to which panel reviews each proposal are made by the Co-Chairs of the REB in consultation with REB Coordinators.
The REB examines the budgets of clinical trials in accordance with Tri-Council Policy Statement (TCP) Article 7.3 which states that "REBs shall examine the budgets of clinical trials to assure that ethical duties concerning conflict of interest are respected" and does so from the perspective of :
Inquiries about whether the REB has received your submission, status updates and administrative inquiries should be directed to reb@uhnresearch.ca or to the REB mainline at 416 581-7849.
Mailing Address: 700 Bay Street LuCliff Place, 17th Floor, Suite 1700-1 Toronto, Ontario M5G 1Z6
The REB fee is levied and collected by Research Solutions and Services through Grant and Contract Services and is used to partially offset the costs incurred by Research Solutions and Services in providing support to the REB. For more information, please see the Grant and Contract Services FAQ.
New study applications must be submitted via CAPCR . Currently, all other submissions (e.g. renewals, amendments, unanticipated event forms etc.) must be submitted directly to the REB at rebsubmissions@uhnresearch.ca for review.
A consent form for pregnancy follow up must be submitted in the event of pregnancy. Considering it is rare that research participants (or their partners) become pregnant while participating in a clinical research study, to facilitate review and approval process, the REB does not recommend submitting a consent form for pregnancy follow with the initial submission, unless required by the study objectives.
When revising documents that have been reviewed by the REB, the requested revisions should be tracked and made on a clean copy the REB reviewed document. Please ensure that the version dates of the document are updated. Once all the revisions have been completed, send both a ‘tracked’ copy and a ‘clean’ copy of the document back to the REB. Please note that the REB will not accept documents that include both new revisions and the revisions that were previously reviewed by the REB.
Consent is an ongoing process and participants should be provided with any and all new information that may influence their consent. New information may be provided, verbally or otherwise, to participants prior to receiving REB approval if the Principal Investigator:
It is the nature of research that answers often lead to more questions and the REB review element of research is no different. An REB review is an iterative process between the PI and the REB which continues until such time as all elements have been satisfactorily addressed. In the course of review, information provided by the study team may result in requests from the REB: a) to modify elements of the study b) for more information At the conclusion of the review, the REB will provide one of the following decisions concerning the study: a) Approved b) Not Approved c) Approval Not Required Please see the link http://intranet.uhnresearch.ca/service/understanding-review-process which describes the review process.
*Please note that deadlines are only provided for initial submissions. Should any Amendments or Renewals need to be considered for review during a Full Board meeting, they must be submitted 2 weeks prior to the appropriate Board’s deadline date.
Biomedical A | Monday January 15, 2024 | Wednesday December 27, 2023 | Wednesday December 13, 2023 |
Rehabilitation Medicine Panel D | Wednesday January 24, 2024 | Friday January 05, 2024 | Friday December 29, 2023 |
Oncology | Friday January 26, 2024 | Friday January 12, 2024 | Friday December 29, 2023 |
Biomedical B | Monday January 29, 2024 | Wednesday January 10, 2024 | Wednesday December 27, 2023 |
Biomedical A | Monday February 12, 2024 | Wednesday January 24, 2024 | Wednesday January 10, 2024 |
Oncology | Friday February 23, 2024 | Friday February 09, 2024 | Friday January 26, 2024 |
Biomedical B | Monday February 26, 2024 | Wednesday February 07, 2024 | Wednesday January 24, 2024 |
Rehabilitation Medicine Panel D | Wednesday February 28, 2024 | Friday February 09, 2024 | Friday February 02, 2024 |
Biomedical A | Monday March 04, 2024 | Wednesday February 14, 2024 | Wednesday January 31, 2024 |
Oncology | Friday March 22, 2024 | Friday March 08, 2024 | Friday February 23, 2024 |
Biomedical B | Monday March 25, 2024 | Wednesday March 06, 2024 | Wednesday February 21, 2024 |
Rehabilitation Medicine Panel D | Wednesday March 27, 2024 | Friday March 08, 2024 | Friday March 01, 2024 |
Biomedical A | Monday April 15, 2024 | Wednesday March 27, 2024 | Wednesday March 13, 2024 |
Rehabilitation Medicine Panel D | Wednesday April 24, 2024 | Friday April 05, 2024 | Tuesday April 2nd, 2024 |
Oncology | Friday April 26, 2024 | Friday April 12, 2024 | Tuesday April 2nd, 2024 |
Biomedical B | Monday April 29, 2024 | Wednesday April 10, 2024 | Wednesday March 27, 2024 |
Biomedical A | Monday May 13, 2024 | Wednesday April 24, 2024 | Wednesday April 10, 2024 |
Rehabilitation Medicine Panel D | Wednesday May 15, 2024 | Friday April 26, 2024 | Friday April 19, 2024 |
Oncology | Friday May 24, 2024 | Friday May 10, 2024 | Friday April 26, 2024 |
Biomedical B | Monday May 27, 2024 | Wednesday May 08, 2024 | Wednesday April 24, 2024 |
Biomedical A | Monday June 10, 2024 | Wednesday May 22, 2024 | Wednesday May 08, 2024 |
Oncology | Friday June 21, 2024 | Friday June 07, 2024 | Friday May 24, 2024 |
Biomedical B | Monday June 24, 2024 | Wednesday June 05, 2024 | Wednesday May 22, 2024 |
Rehabilitation Medicine Panel D | Wednesday June 26, 2024 | Friday June 07, 2024 | Friday May 31, 2024 |
Biomedical A | Monday July 08, 2024 | Wednesday June 19, 2024 | Wednesday June 05, 2024 |
Rehabilitation Medicine Panel D | Wednesday July 24, 2024 | Friday July 05, 2024 | Friday June 28, 2024 |
Oncology | Friday July 26, 2024 | Friday July 12, 2024 | Friday June 28, 2024 |
Biomedical B | Monday July 29, 2024 | Wednesday July 10, 2024 | Wednesday June 26, 2024 |
Biomedical A | Monday August 12, 2024 | Wednesday July 24, 2024 | Wednesday July 10, 2024 |
Oncology | Friday August 16, 2024 *Tentative | Friday August 02, 2024 | Friday July 19, 2024 |
Biomedical B | Monday August 26, 2024 | Wednesday August 07, 2024 | Wednesday July 24, 2024 |
Rehabilitation Medicine Panel D | Wednesday August 28, 2024 | Friday August 09, 2024 | Friday August 09, 2024 |
Biomedical A | Monday September 09, 2024 | Wednesday August 21, 2024 | Wednesday August 07, 2024 |
Rehabilitation Medicine Panel D | Wednesday September 18, 2024 | Friday August 30, 2024 | Friday August 23, 2024 |
Biomedical B | Monday September 23, 2024 | Wednesday September 04, 2024 | Wednesday August 21, 2024 |
Oncology | Friday September 27, 2024 | Friday September 13, 2024 | Friday August 30, 2024 |
Biomedical A | Monday October 07, 2024 | Wednesday September 18, 2024 | Wednesday September 04, 2024 |
Rehabilitation Medicine Panel D | Wednesday October 23, 2024 | Friday October 04, 2024 | Friday September 27, 2024 |
Oncology | Friday October 25, 2024 | Friday October 11, 2024 | Friday September 27, 2024 |
Biomedical B | Monday October 28, 2024 | Wednesday October 09, 2024 | Wednesday September 25, 2024 |
Biomedical A | Monday November 11, 2024 | Wednesday October 23, 2024 | Wednesday October 09, 2024 |
Oncology | Friday November 22, 2024 | Friday November 08, 2024 | Friday October 25, 2024 |
Biomedical B | Monday November 25, 2024 | Wednesday November 06, 2024 | Wednesday October 23, 2024 |
Rehabilitation Medicine Panel D | Wednesday November 27, 2024 | Friday November 08, 2024 | Friday November 01, 2024 |
Rehabilitation Medicine Panel D | Wednesday December 11, 2024 | Friday November 22, 2024 | Friday November 15, 2024 |
Oncology | Friday December 13, 2024 | Friday November 29, 2024 | Friday November 15, 2024 |
Biomedical B | Monday December 16, 2024 | Wednesday November 27, 2024 | Wednesday November 13, 2024 |
REB General Inquiries | 416-581-7849 (18-7849) |
Therese Biggs | Administrative Assistant | 416-581-7849 (REB Mainline) |
Vivian Sandoval | Administrative Assistant | 416-581-7849 (REB Mainline) |
Lorraine Baladjay | Research Studies Coordinator | 416-581-7849 (REB Mainline) | Panel A Lead |
Svetlana Tzvetkova | Research Studies Coordinator | 416-581-7849 (REB Mainline) | Panel B Lead |
Larissa Potanina | Research Studies Coordinator | 416-581-7849 (REB Mainline) | Panel C Lead, Retrospective Biospecimens Studies, and Unanticipated Problems |
Jasmin Bico-Ponce | Research Studies Coordinator | 416-581-7849 (REB Mainline) | Panel D Lead |
Anthony Aqui | Research Studies Coordinator | 416-581-7849 (REB Mainline) | Delegated Lead |
Research Studies Coordinator | 416-581-7849 (REB Mainline) | ||
Kristina Commisso | Research Studies Coordinator | 416-581-7849 (REB Mainline) | |
Wesley Ghent | Research Studies Coordinator | 416-581-7849 (REB Mainline) | |
Nadia Reider | Research Studies Coordinator | 416-581-7849 (REB Mainline) |
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Tiffany Ganesh | Research Studies Coordinator | 416-581-7849 (REB Mainline) | |
Elif Cizmeci | Research Studies Coordinator | 416-581-7849 (REB Mainline) | |
Ralph Pastore | Research Analyst | 416-581-7849 (REB Mainline) |
Paul MacPherson | Director, Grants, Contracts and Ethics Review Services | 416-581-8573 (18-8573) |
Anita Sengar | Manager, REB Operations | 416-581-7849 (REB Mainline) |
Alexander Karabanow | Manager, Clinical Research Services | 416-581-7525 |
Dr. Morris Sherman | Chair, Research Ethics Board | 416-586-4800 (17-8495) | Panels A & B: Biomedical |
Dr. David Hogg | Chair, Research Ethics Board | 416-581-7849 (REB Mainline) | Panel C: Oncology |
Dr. Paul Oh | Chair, Research Ethics Board | 416-581-7849 (REB Mainline) | Panel D: Rehabilitation Med |
Dr. Connie Marras | Vice-Chair, Research Ethics Board | 416-603-6422 (13-6422) | Panel A: Biomedical |
Dr. Jean Wang | Vice-Chair, Research Ethics Board | 416-581-7849 (REB Mainline) | Panel B: Biomedical |
Dr. Eitan Amir | Vice-Chair, Research Ethics Board | 416-581-7849 (REB Mainline) | Panel C: Oncology |
Dr. Catriona Steele | Vice-Chair, Research Ethics Board | 416-581-7849 (REB Mainline) | Panel D: Rehabiliation Med |
This template/guidance document aligns with the Clinical Trials Ontario consent form template.
| |
REB-created document to aid in the creation of an addendum to an existing study specific consent form. |
Instructions for writing Case Reports. | |
Guidelines, definitions and instructions on providing new information to participants. Version date: August 22, 2017 | |
UHN Guidance on Pregnancy Prevention | |
UHN-REB Guidance on Submitting an Investigator's Brochure / Product Monograph | |
UHN-REB Guidance on how to advise the REB of a conflict of interest as per management plan issued by UHN Compliance Office | |
Ethical Considerations for Remote Consent Version date: August 6, 2024 | |
Return of Results to Participants- Version date: July 20th, 2022 |
Memo stating the UHN REBs policy on signing the REB Attestation Form | |
Sample Prospective Protocol for guidance. | |
Sample Chart Review Protocol for guidance | |
Sample TIssue Protocol for guidance | |
Pregnancy Prevention Information Sheet | |
Remote Monitoring Participant Notification letter | |
UHN guidance on the options for obtaining research consent remotely as a safety measure due to COVID-19. Version date: March 08, 2021 |
When conducting clinical trials in Canada, a Sponsor must generally possess, for each clinical trial site, a Research Ethics Board Attestation (REBA), which provides administrative information regarding the research ethics board (REB) as well as a certification that its composition, operations and decisions are in compliance with Canadian regulations.
A REBA must also be completed for each clinical trial site whenever the clinical trial application is amended (for example when modifications have been incorporated to the Clinical Study Protocol). Therefore the completion, collection, and tracking of the REBAs may represent an administrative challenge in the context of a multicenter trial for both the Sponsor and the Sites.
As part of its commitment to keeping studies on TRACK TM and to reduce the record-keeping burden on Sponsors/CROs and Sites, Veritas IRB has incorporated the Health Canada ‘Research Ethics Board Attestation’ (REBA) text into its Approval Forms. This is permitted by Health Canada , which specifies that the IRB Approval Form ‘does not need to include all the elements contained in Part 1, Part 2 and Part 3 of the REBA Form’.
Veritas IRB incorporates the REBA text into its Approval Forms only for the unconditional approval of a research Site – or for the implementation of a Protocol Amendment at the Site – for research being conducted under a Health Canada No Objection Letter (NOL). There is no equivalent requirement for device research being conducted under a Health Canada Investigational Testing Authorization (ITA).
For multicenter trials, the REBA text is incorporated only into Veritas IRB’s Site-specific Approval Forms, and not into any of the central- or study-level Approval Forms, because the REBA is Site-specific in nature. Section 3 of the REBA text states: ‘… for the trial which is to be conducted by the qualified investigator named above at the specified clinical trial site …’
The Veritas IRB Editorial Board covers questions of research ethics, clinical trial conduct, and human research participant protection primarily for sponsors, CROs and investigators/researchers. // Le blogue de Veritas IRB aborde des questions de l'éthique de la recherche, de la bonne conduite des essais cliniques, et de la protection des participants à la recherche dans une perspective axée sur les promoteurs de la recherche, les organismes de recherche sous contrat (ORCs ou CROs), et les chercheurs.
Country selection
Scope of assessment, regulatory fees, ethics committee, scope of review, ethics committee fees, oversight of ethics committees.
Clinical Trial Lifecycle
Submission content, timeline of review, initiation, agreements & registration, safety reporting, progress reporting.
Sponsorship
Site/investigator selection, insurance & compensation, risk & quality management, data & records management, personal data protection.
Informed Consent
Required elements, participant rights, emergencies, vulnerable populations, children/minors, pregnant women, fetuses & neonates, mentally impaired.
Investigational Products
Manufacturing & import, quality requirements, product management, definition of specimen, specimen import & export, consent for specimen, requirements, additional resources.
Clinical Trials Registries
Ethics Committees
Funding & Institutions
Canada profile updated in clinregs, health canada issues notice for clinical trials impacted by covid-19.
Other Regulatory Databases
Health Canada
As per the CanadaFDA , the CanadaFDR , and the G-CanadaCTApps , Health Canada (HC) is the competent authority responsible for clinical trial approvals, oversight, and inspections in Canada. The G-CanadaCTApps states that the HC grants permission for clinical trials to be conducted in the country, and regulates the sale and importation of drugs for use in clinical trials in accordance with the CanadaFDR provisions.
As per CAN-29 , HC is one (1) of five (5) federal agencies within Canada’s “Health Portfolio” overseen by the Minister of Health. Per CAN-31 , HC assesses clinical trial protocols to evaluate participant protection and safety; reviews drug quality; assures institutional ethics committee review; verifies principal investigator qualifications; and monitors and reviews adverse drug reactions. As delineated in CAN-23 , HC’s Health Products and Food Branch (HPFB) is the national authority that regulates, evaluates, and monitors therapeutic and diagnostic product safety, efficacy, and quality, and reviews the information submitted in the clinical trial application.
Per CAN-16 , HPFB’s activities are carried out by nine (9) Directorates and one (1) office, including the Pharmaceutical Drugs Directorate (PDD) and the Biologic and Radiopharmaceutical Drugs Directorate (BRDD) . Per CAN-18 and CAN-17 , the PDD and the BRDD, respectively, regulate pharmaceutical drugs, and biological drugs and radiopharmaceuticals for human use. In addition, the G-CanadaCTApps indicates that the PDD’s Office of Clinical Trials (OCT) and the BRDD’s Office of Regulatory Affairs (ORA), among others, are directly involved with the clinical trial review and approval process for pharmaceutical, biological, and radiopharmaceutical drugs. Per the G-MDSA , the Therapeutic Products Classification Committee (TPCC) may be consulted when it is not clear whether a product should be classified as a drug or device. The committee makes recommendations on the classification of a product as either a drug, medical device, or combination product. If a product does not readily meet one (1) of the statutory definitions, other regulatory areas of HC are asked to participate in the committee's discussion.
As per CAN-41 , Health Canada has established a regulatory innovation agenda, which aims to provide more regulatory flexibility to support innovative research and health product development. For more details, see CAN-41 .
Per CAN-10 , Canada is an official member of the International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH). HC-implemented ICH guidelines take precedence over other HC guidance when they are not consistent. See HCNotice-CA-ICH-GCP for information on Canada’s implementation of the CA-ICH-GCP . Also see CAN-10 for details on all the ICH guidelines implemented by HC. For any questions or comments, contact HC’s ICH Coordinator via email at [email protected] .
Contact Information
According to the G-DrugApp and CAN-18 , Health Canada PDD contact information is as follows:
Office of Clinical Trials Pharmaceutical Drugs Directorate Health Products and Food Branch Address Locator: 3105A Health Canada Ottawa, Ontario, Canada K1A 0K9
Phone (General Enquiries): 613-957-0368 Fax (General Enquiries): 613-952-7756 Office of Clinical Trials Inquiries: [email protected]
Per CAN-17 , the following is the contact information for biologic clinical trials:
Biologic and Radiopharmaceutical Drugs Directorate Health Products and Food Branch Health Canada Building 6, Address Locator: 0601B 100 Eglantine Driveway Tunney’s Pasture Ottawa, Ontario, Canada K1A 0K9
Phone: 613-863-8405 General Enquiries E-mail: [email protected]
In accordance with the CanadaFDA , Health Canada (HC) reviews, evaluates, and approves applications for clinical trials using authorized therapeutic products. HC also approves the sale or importation of drugs for use in clinical trials. (See the Manufacturing & Import section for additional information on importation.) As delineated in the CanadaFDR and the G-CanadaCTApps , institutional ethics committee (EC) review is required for each clinical trial site and may occur in parallel with HC’s clinical trial application (CTA) review and approval. For HC’s interpretation of the relevant provisions of the CanadaFDR , see the G-FDR-0100 . See CAN-23 and CAN-19 for background information on HC’s scope of assessment.
Per the CanadaFDA , a “therapeutic product” is defined as a drug or device, or any combination of drugs and devices, but does not include natural health products; and “therapeutic product authorization” refers to a license that is approved for the import, sale, advertisement, manufacture, preparation, preservation, packaging, labeling, storage, or testing of a therapeutic product. As per the G-CanadaCTApps , a drug is defined as a pharmaceutical, biologic, gene therapy, blood product, vaccine, and radiopharmaceutical for human use that is to be tested in a clinical trial. HC’s scope of assessment includes clinical trials (Phases I - III) using:
Clinical Trial Review Process
As set forth in the G-CanadaCTApps and CAN-23 , HC’s Health Products and Food Branch (HPFB) coordinates the CTA approval process. The G-CanadaCTApps and CAN-23 state that prior to initiating the trial, the sponsor must file a CTA to the appropriate HPFB Directorate. CTAs involving pharmaceutical drugs should be sent to the Pharmaceutical Drugs Directorate (PDD) , and CTAs involving biologics and/or radiopharmaceuticals should be sent to the Biologic and Radiopharmaceutical Drugs Directorate (BRDD) .
The G-CanadaCTApps and CAN-23 indicate that upon receipt of a CTA, the HPFB Directorate (PDD/BRDD) screens the application package for completeness. If deficiencies are found, the Directorate sends the sponsor a Request for Clarification or a Screening Rejection Letter. If the Directorate finds the application complete, an acknowledgement letter is issued to indicate the 30-day default review period commenced on the date of receipt.
Per the G-CanadaCTApps , once a clinical trial is authorized, the sponsor is allowed to sell or import a drug for use in a trial, if a CTA has been filed with HC and has not received an objection within 30 days. As delineated in the G-CanadaCTApps and CAN-23 , if the clinical trial is authorized, a No Objection Letter (NOL) is issued. If the CTA is rejected, a Not Satisfactory Notice (NSN) is issued. As specified in the G-CanadaCTApps and CAN-23 , during the review period, the Directorate may request additional information from the sponsor, who has two (2) calendar days to provide such information. Please see the G-CanadaCTApps for special requirements regarding reviews of comparative bioavailability studies and joint reviews of clinical trials covering a combination of devices, biologics, and pharmaceuticals. See the Submission Process section for detailed application submission requirements.
Per the G-CanadaCTApps , soon after HC issues an NOL, it will publish the following information about the clinical trial in HC’s publicly accessible database:
The CanadaFDR and the G-CanadaCTApps also delineate that a clinical trial application-amendment (CTA-A) is required for proposed changes to a previously authorized study when the changes to clinical trial drug supplies affect the quality or safety of the drug, or when the changes to an authorized protocol alter the risk to clinical trial participants, or both. CTA-As must be authorized by HC prior to implementation of the changes. However, if the sponsor is required to immediately implement changes because the clinical trial or the use of the clinical trial drug endangers the health of participants or other persons, the sponsor may immediately make the amendment without prior review by HC. Sponsors must notify HC of this change, provide the relevant rationale in support of the immediate implementation, and file a CTA-A that clearly identifies the change and rationale for immediate implementation of the change within 15 days after the amendment implementation date. In addition, sponsors may make the following changes immediately if it notifies HC in writing within 15 days after the date of the change: a change to the chemistry and manufacturing information that does not affect the quality or safety of the drug; or a change to the protocol that does not alter the risk to the health of a participant.
Per the CanadaFDR , HC will suspend the authorization to sell or import a drug for clinical trial purposes if it has reasonable grounds to believe that:
See the CanadaFDR for additional details on HC’s suspension and cancellation responsibilities.
According to CAN-33 , there are no fees to submit a clinical trial application in Canada.
As indicated in the CanadaFDR and the G-CanadaCTApps , Canada has a decentralized process for the ethical review of clinical trial applications, and requires the sponsor to obtain institutional ethics committee (EC) approval for each participating trial site. (Note: institutional ECs are referred to as Research Ethics Boards (REBs) in Canada.) Canadian provinces may have varying requirements, and, therefore, the sponsor should consult with the applicable province(s) for more information.
Per CAN-35 and CAN-13 , all proposed or ongoing research involving human participants carried out by, funded by, or otherwise under the auspices of Health Canada (HC) or the Public Health Agency of Canada (PHAC) must obtain approval from a joint EC representing those two (2) agencies—as well as complying with the CanadaFDR and the CA-ICH-GCP . This joint EC is known as the HC-PHAC REB. Further, if an institution is conducting an HC- or PHAC-funded project, the HC-PHAC REB must review and approve the research even if it has been previously reviewed and approved by another EC. See CAN-35 for details on the HC-PHAC REB’s development, responsibilities, and composition. HC’s operational policy ( CAN-13 ) outlines policies and procedures that the joint HC-PHAC REB must follow when reviewing clinical trials.
Institutional ECs are required to comply with the provisions delineated in the CanadaFDR , the G-CanadaCTApps , and the CA-ICH-GCP . See HCNotice-CA-ICH-GCP for more information on Canada’s implementation of the CA-ICH-GCP . Note that per HCNotice-CA-ICH-GCP , HC-implemented International Council for Harmonisation (ICH) guidance takes precedence over other HC guidance when they are not consistent. For HC’s interpretation of the relevant provisions of the CanadaFDR , see the G-FDR-0100 . In addition, institutional ECs are guided by the G-TCPS2 . Jointly developed by Canada’s three (3) federal research agencies: the Canadian Institutes of Health Research (CIHR) , the Natural Sciences and Engineering Research Council of Canada (NSERC) , and the Social Sciences and Humanities Research Council (SSHRC) , the G-TCPS2 is a policy that sets the ethical benchmark for all Canadian institutional ECs. However, only CIHR-, NSERC-, and SSHRC-funded institutions are required to comply with this guideline as a condition of funding. According to CAN-14 , the CIHR, the NSERC, and the SSHRC created the Panel on Research Ethics (PRE) to promote the ethical conduct of research involving human participants. The PRE develops, interprets, and implements the G-TCPS2 .
Ethics Committee Composition
As delineated in the CanadaFDR , the G-CanadaCTApps , and the CA-ICH-GCP , institutional ECs must have at least five (5) members representing a mixed gender composition, the majority of which are Canadian citizens or permanent residents, and must include:
The G-TCPS2 mirrors these EC composition requirements. As mentioned earlier, only CIHR-, NSERC-, and SSHRC-funded institutions are required to comply with this guidance as a condition of funding.
Terms of Reference, Review Procedures, and Meeting Schedule
According to the CA-ICH-GCP , institutional ECs must establish written standard operating procedures (SOPs) to cover the entire review process. The SOPs should include EC composition, meeting schedules, notifications, frequency of reviews, protocol deviations, reporting to the EC, and recordkeeping. Further, ECs should make decisions at announced meetings where a quorum is present. Only those members who participate in the EC review and discussion should vote, provide their opinion, or advise. For detailed EC procedures and information on other administrative processes, see the CA-ICH-GCP . For examples of EC SOPs, see CAN-13 for the HC-PHAC REB operational policy.
According to the CanadaFDR , the G-CanadaCTApps , the G-TCPS2 , and the CA-ICH-GCP , the primary scope of information assessed by institutional ethics committees (ECs) (called Research Ethics Boards (REBs) in Canada) relates to maintaining and protecting the dignity and rights of human research participants and ensuring their safety throughout their participation in a clinical trial. ECs must also pay special attention to reviewing informed consent and protecting the welfare of certain classes of participants deemed vulnerable. (See the Vulnerable Populations; Children/Minors; Pregnant Women, Fetuses & Neonates; Prisoners; and Mentally Impaired sections for additional information about these populations.) Note that per HCNotice-CA-ICH-GCP , Health Canada (HC) -implemented International Council for Harmonisation (ICH) guidance takes precedence over other HC guidance when they are not consistent.
The CA-ICH-GCP also state that ECs must ensure an independent, timely, and competent review of all ethical aspects of the clinical trial protocol. They must act in the interests of the potential research participants and the communities involved by evaluating the possible risks and expected benefits to participants, and they must verify the adequacy of confidentiality and privacy safeguards. See the CA-ICH-GCP for detailed ethical review guidelines.
Role in Clinical Trial Approval Process
As per the CanadaFDR and the CA-ICH-GCP , HC must approve a clinical trial application (CTA) and an institutional EC(s) must give ethical clearance prior to a sponsor initiating a clinical trial. In addition, as delineated in the CanadaFDR and the G-CanadaCTApps , institutional EC review for each clinical trial site may occur in parallel with HC’s CTA review and approval. Once HC completes its review, the department issues a No Objection Letter (NOL) if the CTA is approved. However, per the CanadaFDR , the G-CanadaCTApps , CAN-6 , and CAN-30 , HC will not authorize the sponsor to begin the clinical trial until an institutional EC approval for each participating trial site is submitted. The sponsor should use the Clinical Trial Site Information Form ( CAN-6 ) to submit the required information. The CanadaFDR also states that the EC must review and approve any protocol amendments prior to those changes being implemented. For HC’s interpretation of the relevant provisions of CanadaFDR , see the G-FDR-0100 .
The G-TCPS2 , which sets the ethical benchmark for all Canadian institutional ECs, requires EC review and approval of research involving living human participants and human biological materials. Further, ECs must have procedures in place to receive and respond to reports of new information, including, but not limited to, safety data, unanticipated issues, and newly discovered risks.
See TCPS2-InterpReview for the Panel on Research Ethics (PRE) ’s interpretations of the G-TCPS2 , including on the EC’s review of secondary use of non-identifiable information, delegated review of minimal risk studies, and ongoing review.
The G-TCPS2 lays out options, procedures, and considerations for the ethics review of multi-jurisdictional research either entirely within Canada, or in Canada and other countries. An institutional EC may approve alternative review models for research with multiple ECs and/or institutions but remains responsible for the ethics and conduct of research in its jurisdiction or under its auspices regardless of where the research is conducted. See the G-TCPS2 for more information about the various review models for multi-jurisdictional research.
Per CAN-8 , an attestation must be completed by the EC that reviewed and approved the clinical trial. The completed attestation must be retained by the clinical trial sponsor for a period of 15 years. The attestation should not be submitted to HC unless requested. (See the Submission Process section for detailed submission requirements.)
The G-TCPS2 directs the researcher to submit an annual report to enable the EC to evaluate the continued ethical acceptability of the research. Per the G-CanadaCTApps , in the event that an EC terminates or suspends any prior approval or favorable opinion, it must document its views in writing, clearly identifying the trial, the documents reviewed, and the date for the termination or suspension.
Institutional ethics committees (ECs) may independently decide whether to charge fees to conduct protocol reviews. For example, an institutional EC may require industry sponsors or other for-profit organizations to pay a fee. See specific examples of institutional fee requirements in CAN-3 and CAN-1 .
There are no applicable regulations or guidance regarding the registration, auditing, and accreditation of institutional ethics committees (ECs).
In accordance with the CanadaFDR and the G-CanadaCTApps , Canada requires the sponsor to obtain clinical trial authorization from Health Canada (HC) prior to initiating the trial. The sponsor must file a clinical trial application (CTA) to the appropriate Directorate within HC’s Health Products and Food Branch (HPFB) . In addition, as delineated in the CanadaFDR and the G-CanadaCTApps , the sponsor may submit a CTA for clinical trial authorization to the HC in parallel with its submission to an institutional ethics committee (EC) (known as a Research Ethics Board (REB) in Canada) for a favorable ethical opinion. However, per the CanadaFDR , the G-CanadaCTApps , CAN-6 , and CAN-30 , HC will not authorize the sponsor to begin the clinical trial until an institutional EC approval (provided in the required Clinical Trial Site Information (CTSI) form ( CAN-6 )) for each participating trial site is submitted. The HCNotice-CTSIForm indicates that the CTSI form improves efficiencies and supports the submission of CTAs using the electronic Common Technical Document (eCTD) format. See CAN-30 for instructions on filling out and submitting CAN-6 .
CAN-19 provides a full list of HC’s forms for drug-related applications and submissions. For HC’s interpretation of the relevant provisions of the CanadaFDR , see the G-FDR-0100 .
Regulatory Submission
Per the G-CanadaCTApps , CTAs ( CAN-4 ) should be sent directly to the appropriate HPFB Directorate for review—the Pharmaceutical Drugs Directorate (PDD) for pharmaceutical drugs or the Biologic and Radiopharmaceutical Drugs Directorate (BRDD) for biological drugs and radiopharmaceuticals. The outer label should be clearly identified with "Clinical Trial Application." Per CAN-44, applicants must submit CTAs electronically in either eCTD format or non-eCTD format. According to the G-MDSA , HC does not accept paper copies of CTAs, CTA amendments, and CTA notifications.
The G-MDSA and the G-CanadaCTApps indicate that sponsors may request a pre-submission/application meeting with the appropriate Directorate within the HPFB if they have any questions or concerns prior to filing a CTA. Additional details on requesting a meeting and meeting procedures are available in the aforementioned guidance documents. According to CAN-4 , the submission can be in French or English. For CTAs that use pharmacometric approaches, sponsors should consider the policy statements in G-Pharmacometrics . Pharmacometrics is the science of using quantitative analysis and modelling and simulation approaches to inform and enhance drug development and regulatory review. In addition, see the G-CTACell for guidance on preparing CTAs for use of cell therapy products in humans.
Per the CanadaFDR , an application by a sponsor for authorization to sell or import a drug for the purposes of a clinical trial must be submitted to HC, signed and dated by the sponsor’s senior medical or scientific officer in Canada and senior executive officer. The sponsor’s clinical trial attestation must be submitted with the application ( CAN-4 ). For guidance on completing CAN-4 , see the G-DrugApp .
eCTD Electronic Submission
As indicated in the G-eCTD, clinical trial applications in eCTD format are recommended, not mandatory. However, once a sponsor files a regulatory activity in eCTD format, all additional information and subsequent regulatory activities for the same dossier must be filed in eCTD format. CAN-36 explains that prior to filing the first regulatory transaction for a dossier in eCTD format, the sponsor must request a dossier ID using the online dossier ID request. Per the ElecSubms , CAN-20 is the request form for biological clinical trial dossiers and CAN-21 is for pharmaceutical clinical trial dossiers. A request for a dossier ID should be sent a maximum of eight (8) weeks prior to submitting the CTA. In addition, applicants should review the Rules-eCTD for validation rules before submission. (Note: As per ElecSubms , G-eCTD and CAN-36 are only available upon request at [email protected] . Please ensure the text 'Request for eCTD Guidance Document' is in the subject line of the email.)
Per the G-eCTD and CAN-28 , all regulatory transactions in eCTD format must be sent via the Common Electronic Submissions Gateway (CESG) ( CAN-25 ), except for those exceeding 10 gigabytes (GB) in size. The CESG allows users to submit secure regulatory transactions electronically to HC, including CTAs. The G-eCTD and CAN-36 describe how to file CTAs and other clinical trial regulatory transactions (e.g., CTA amendments, responses to requests for information, and other in-scope activities) in eCTD format to CESG. The G-eCTD clarifies that prior to using the CESG for sending transactions, sponsors must register as a trading partner. To access and use CESG, CAN-34 instructs sponsors to follow these steps:
For detailed information on how to become a trading partner and send regulatory transactions, refer to CAN-25 and the FDA User Guide ( CAN-47 ).
As indicated in the G-eCTD, the following media formats are acceptable for eCTD transactions greater than 10 GB: Universal Serial Bus (USB) 2.0 or 3.0 drive; or portable external hard drive with USB 2.0 or 3.0 interfaces. (Contact HC at [email protected] for other media formats that may be acceptable at the time of filing.) A paper copy of the cover letter must accompany the media (unless otherwise indicated), and a pre-paid envelope must be provided if the media is to be returned. The complete regulatory transaction must be provided on a single drive, and the label on the drive should contain the following information:
Media must be mailed to HC at the address below:
Health Canada Finance Building 101 Tunney’s Pasture Driveway Address Locator: 0201A1 Ottawa, Ontario K1A 0K9
See the G-CESG, the G-eCTD, CAN-47 , CAN-34 , CAN-36, CAN-25 , and CAN-28 for details on registering as a trading partner for CESG transactions, how to use CESG, and submitting CTAs in eCTD format. (Note: As per ElecSubms , G-CESG is only available upon request at [email protected] . Please ensure the text 'Request for eCTD Guidance Document' is in the subject line of the email.)
Non-eCTD Electronic Submission
For non-eCTD electronic submissions, G-Non-eCTD indicates that HC requires both PDF and MS-Word formats for the CTA ( CAN-4 ). The PDF documents must be generated from electronic sources (not scanned material), except when access to an electronic source document is unavailable or where a signature is required. It is important that PDF files be properly bookmarked and hyperlinked. Documents that legally require signatures may be signed with an electronic signature, or the signature page can be printed, signed, scanned, and saved as a PDF file. The cover letter does not require a signature, but should include a printed name, phone number, and email address. All regulatory submissions should be validated prior to transmitting to HC. For validation rules, see the Rules-Non-eCTD . The ElecSubms contains a zip file of the folder structure for clinical trial non-eCTD submissions. (Note: As per ElecSubms , G-Non-eCTD is only available upon request at [email protected] . Please ensure the text 'non eCTD Guidance Document' is in the subject line of the email.)
Per the G-Non-eCTD , CTA submissions to the appropriate Directorate within HC’s HPFB must be in one (1) of these accepted media formats:
All media should be labelled and contain the following information:
Subsequent to burning the CD/DVD or transferring data to a drive, applicants should ensure that all files can be opened, files are not corrupted, and that "Thumb.db" files are removed.
As per the G-Non-eCTD , CAN-18 , and CAN-17 , non-eCTD CTAs involving pharmaceutical drugs should be sent to PDD, and CTAs involving biologics and/or radiopharmaceuticals should be sent to BRDD at the addresses listed below.
Office of Clinical Trials Pharmaceutical Drugs Directorate Health Canada 5th Floor, Holland Cross, Tower B 1600 Scott Street Address Locator: 3105A Ottawa, Ontario, Canada K1A 0K9 General Inquiries E-mail: [email protected]
Office of Regulatory Affairs Biologic and Radiopharmaceutical Drugs Directorate Ground Floor, Health Canada Building 6 100 Eglantine Driveway Address Locator: 0601C Ottawa, Ontario, Canada K1A 0K9 General Enquiries E-mail: [email protected]
Per the HCNotice-CTSIForm , questions related to pharmaceutical CTSI forms should be sent to: [email protected] and questions related to biologic CTSI forms should be sent to [email protected] .
Per the G-Non-eCTD , if an applicant submits a non-eCTD CTA via email, they should meet the following requirements:
The G-Non-eCTD provides additional information on emailing other clinical trial submissions, including responses to a clarification request, responses to a no objection letter, notifications, and development safety update reports.
Ethics Review Submission
As indicated in the CanadaFDR and the G-CanadaCTApps , all research involving human participants in Canada must be reviewed by an institutional ethics committee (EC). (Note: institutional ECs are referred to as Research Ethics Boards (REBs) in Canada.) Because the submission process at individual institutional ECs will vary, applicants should review and follow their institution’s specific requirements. Further, Canadian provinces may have varying requirements, and, therefore, the sponsor should consult with the applicable province(s) for more information. See CAN-35 for submission requirements to the joint HC- Public Health Agency of Canada (PHAC) ’s REB. This joint EC reviews all research involving human subjects that is carried out by HC or PHAC researchers, on the premises, or in collaboration with external researchers.
Regulatory Authority Requirements
As set forth in the CanadaFDR , the G-CanadaCTApps , and CAN-31 , Health Canada (HC) requires the sponsor to apply for clinical trial authorization by submitting a clinical trial application (CTA) to HC. As specified in the G-CanadaCTApps and the G-QCM-PharmCTAs , the CTA should be organized into three (3) modules in Common Technical Document (CTD) format:
Per the CanadaFDR , the clinical trial application form ( CAN-4 ) and the following information and documents must be submitted:
Refer to the CanadaFDR , the G-CanadaCTApps , the G-DrugApp , the G-QltyBioCTs , and the G-QCM-PharmCTAs for detailed submission information.
Ethics Committee Requirements
Each institutional EC has its own application form and clearance requirements, which can differ significantly regarding the number of copies to be supplied and application format requirements. However, the following requirements comply with the CA-ICH-GCP and are basically consistent across all Canadian ECs:
See section 3.1.2 of CA-ICH-GCP for additional submission content requirements.
The G-TCPS2 , which sets the ethical benchmark for all Canadian institutional ECs, requires clinical trial researchers to include a plan for monitoring safety, efficacy/effectiveness (where feasible), and validity in their proposal for EC review. See the G-TCPS2 for additional details on the plan’s required contents.
See CAN-35 for submission requirements to the joint HC- Public Health Agency of Canada (PHAC) 's REB. This joint EC reviews all research involving human subjects that is carried out by HC or PHAC researchers, on the premises, or in collaboration with external researchers.
Clinical Protocol
As delineated in the CA-ICH-GCP , the clinical protocol should include the following elements:
For complete protocol requirements, see section 6 of CA-ICH-GCP .
As delineated in the CanadaFDR and the G-CanadaCTApps , the review and approval of a clinical trial application (CTA) by Health Canada (HC) and an institutional ethics committee (EC) (known as Research Ethics Board (REB) in Canada) may be conducted in parallel. However, per the CanadaFDR , the G-CanadaCTApps , CAN-6 , and CAN-30 , HC will not authorize the sponsor to begin the clinical trial until an institutional EC approval (provided in the required Clinical Trial Site Information (CTSI) form) for each participating trial site is submitted. For HC’s interpretation of the relevant provisions of the CanadaFDR , see the G-FDR-0100 .
Regulatory Authority Approval
According to the CanadaFDR and the G-CanadaCTApps , an authorized clinical trial is one that has been filed with HC and has not received an objection within 30 days. All CTAs are subject to the 30-day default period from the date of receipt of the completed application at the appropriate Directorate within HC’s Health Products and Food Branch (HPFB) . While the Directorates can establish shorter administrative targets of seven (7) days for the review of bioequivalence trials, the 30-day default system remains the regulatory requirement. Applications to conduct Phase I clinical trials using somatic cell therapies, xenografts, gene therapies, prophylactic vaccines, or reproductive and genetic technologies are not included in the seven-day target system. Please see the G-CanadaCTApps for special requirements regarding reviews of comparative bioavailability studies and joint reviews of clinical trials covering a combination of devices, biologics, and pharmaceuticals.
As specified in the G-CanadaCTApps and the G-MDSA , during the review period, the Directorate may request additional information from the sponsor, who has two (2) calendar days to provide such information. The G-MDSA clarifies that, where warranted, HC can adjust the timelines to be longer or shorter based on the complexity of the request, dialogue with the sponsor, and/or circumstances of the review, including pausing the clock during the scientific review. According to the G-CanadaCTApps and the G-MDSA , if HC authorizes the CTA, then it issues a No Objection Letter (NOL). If HC rejects the CTA, it sends a Not Satisfactory Notice (NSN). HC will issue an NSN if it identifies significant deficiencies, or, if a timely response to requested information has not been provided. The sponsor may resubmit the information and material at a future time, and it will be processed as a new CTA.
Ethics Committee Approval
The EC review and approval process timeline varies by institution. However, according to the CA-ICH-GCP , the institutional EC should review a proposed clinical trial within a reasonable time. The G-TCPS2 , which sets the ethical benchmark for all Canadian institutional ECs, recommends a proportionate approach to ethics review—the lower the level of risk, the lower the level of scrutiny (delegated review); the higher the level of risk, the higher the level of scrutiny (full board review). In either case, pursuant to the G-TCPS2 , the institutional EC should make its decisions in an efficient and timely manner. See CAN-35 for ethics review timelines with the joint HC- Public Health Agency of Canada (PHAC) 's REB. This joint EC reviews all research involving human subjects that is carried out by HC or PHAC researchers, on the premises, or in collaboration with external researchers.
In accordance with the CanadaFDR and the G-CanadaCTApps , a clinical trial can only commence after the sponsor receives authorization from both Health Canada (HC) and an institutional ethics committee (EC) (known as Research Ethics Board (REB) in Canada). No waiting period is required following the applicant’s receipt of these approvals. CAN-30 specifies that for purposes of the Clinical Trial Site Information (CTSI) Form ( CAN-6 ), the trial commencement date is the date when the clinical trial site is ready to enroll participants. The commencement date is a date after which the sponsor has both the HC authorization from the appropriate Directorate (date on the No Objection Letter (NOL)) and approval from the relevant EC. Further, the commencement date would be the date when the sponsor implements the protocol, which includes the screening period that occurs prior to the check-in date. See the Scope of Review section for detailed institutional EC requirements, and the Submission Content section for additional HC approval information. For HC’s interpretation of the relevant provisions of the CanadaFDR , see the G-FDR-0100 .
In addition, per the G-CanadaCTApps , if a sponsor (Canadian or foreign) wants to import a drug into Canada to conduct a clinical trial, a copy of HC’s clinical trial authorization (i.e., the NOL) must be included with the drug shipment. According to the G-CanadaCTApps and CAN-32 , if a sponsor plans to import investigational drugs directly to each trial site, then the sponsor must also authorize the importer (i.e., the clinical trial site) when submitting the clinical trial application using Appendix I of HC’s Drug Submission Application Form ( CAN-4 ). See the Manufacturing & Import section for detailed import requirements.
Clinical Trial Agreement
Prior to initiating the trial, as delineated in the G-FDR-0100 and the CA-ICH-GCP , the sponsor must sign an agreement between all involved parties, including ECs, Qualified Investigators (QIs), contract research organizations, and others, to ensure full compliance with the regulatory requirements. Further, the sponsor should obtain the investigator’s/institution's agreement:
The sponsor and the investigator/institution should sign the protocol, or an alternative document, to confirm this agreement.
In accordance with the G-CanadaCTApps , prior to initiating a clinical trial, the sponsor must ensure that a Qualified Investigator Undertaking (QIU) form ( CAN-37 or similar documentation that meets the CanadaFDR requirements) has been completed and is kept on file by the sponsor. Per the CanadaFDR , the form certifies that the QI will conduct the clinical trial in accordance with good clinical practice and will immediately inform trial participants and the institutional EC of trial discontinuance and the reason for this discontinuance. If there is a change in the QI at a site, a new CTSI Form must be submitted to HC, and a new QIU form must be maintained by the sponsor.
See CAN-6 , CAN-8 , and CAN-19 for additional clinical trial forms.
Clinical Trial Registration
As per the G-CanadaCTApps , sponsors should register their clinical trials on one (1) of two (2) publicly accessible registries accepting international clinical trial information and recognized by the World Health Organization (WHO) , ClinicalTrials.gov ( CAN-45 ), and the International Standardized Randomized Controlled Trial Number (ISRCTN) Registry ( CAN-46 ). According to HCNotice-CTRegDisc , clinical trial registration is not a mandatory requirement at this time. However, per the G-TCPS2 , which sets the ethical benchmark for all Canadian institutional ECs, clinical trials must be registered before recruitment of the first trial participant in a publicly accessible registry that is acceptable to the WHO or the International Committee of Medical Journal Editors (ICMJE) . In addition, following registration, researchers are responsible for ensuring that the registry is updated in a timely manner with: new information; safety and, where feasible, efficacy reports; reasons for stopping a trial early; and the location of findings.
Safety Reporting Definitions
According to the CanadaFDR and G-CanadaCTApps , and the CA-ICH-GCP , the following definitions provide a basis for a common understanding of Canada’s safety reporting requirements:
The G-TCPS2 , which sets the ethical benchmark for all Canadian institutional ethics committees (ECs), requires researchers to promptly report new information revealed during the conduct of the trial that might affect the welfare or consent of participants to the EC, to a publicly accessible registry, and to other appropriate regulatory or advisory bodies. In addition, when new information is relevant to participants’ welfare, researchers must promptly inform all participants to whom the information applies (including former participants). Researchers must work with their ECs to determine which participants must be informed, and how the information should be conveyed.
For Health Canada (HC) ’s interpretation of the relevant provisions of the CanadaFDR , see the G-FDR-0100 .
Safety Reporting Requirements
Investigator Responsibilities
Per the CA-ICH-GCP , all SAEs should be reported immediately to the sponsor except for those SAEs that the protocol or other document (e.g., Investigator's Brochure) identifies as not needing immediate reporting. The immediate reports should be followed promptly by detailed, written reports. The immediate and follow-up reports should identify participants by unique code numbers assigned to the trial subjects rather than by their names, personal identification numbers, and/or addresses. The investigator should also comply with the applicable regulatory requirement(s) related to the reporting of unexpected serious ADRs to the regulatory authority(ies) and the EC. AEs and/or laboratory abnormalities identified in the protocol as critical to safety evaluations should be reported to the sponsor according to the reporting requirements and within the time periods specified by the sponsor in the protocol. For reported deaths, the investigator should supply the sponsor and the EC with any additional requested information (e.g., autopsy reports and terminal medical reports).
Sponsor Responsibilities
As delineated in the CanadaFDR , the G-CanadaCTApps , the HCNotice-E2A , and CAN-22 , the sponsor is required to expedite reports of ADRs to HC that meet these three (3) criteria: serious, unexpected, and having a suspected causal relationship. ADR reports that are expected or unexpected, but not serious, should not be reported to HC, but rather monitored and tracked by the sponsor. Further detail and clarifications on AE/ADR reporting criteria can be found in the HCNotice-E2A and CAN-22 . As specified in the G-CanadaCTApps and the HCNotice-E2A , when evaluating whether an AE is serious and unexpected, the Qualified Investigator’s (QI) and sponsor’s determination of causality is important. Only serious and unexpected ADRs found to have a reasonable suspected causal relationship to the drug should be reported by the sponsor to HC.
Per the CanadaFDR and the G-CanadaCTApps , during a clinical trial, the sponsor is required to inform HC of any serious, unexpected ADR that has occurred inside or outside Canada. An ADR report must be filed in the following specified timelines:
Other Safety Reports
The G-DSUR delineates that the development safety update report (DSUR) and the DSUR Checklist ( CAN-38 ) should be provided when requested by HC. A DSUR may be submitted voluntarily to HC when important new safety information on a drug needs to be conveyed by a clinical trial sponsor. In these cases, a rationale/justification for the filing of the DSUR should be included in the cover letter. For additional details, see the G-DSUR .
The G-DSUR-CanUK describes the region-specific requirements for DSURs submitted to the regulatory authorities of Canada and the United Kingdom. This guidance applies to both marketed and non-marketed drugs that are used in clinical trials and applies to DSURs prepared by the manufacturer and/or marketing authorization holder of the investigational drug.
Form Completion & Delivery Requirements
As per the G-CanadaCTApps , the HCNotice-E2A , and CAN-22 , all serious and unexpected ADRs should be reported individually to HC. According to HC-ICH-E2A (which Canada adopted pursuant to the HCNotice-E2A ), at a minimum, the report should include an identifiable patient, the name of a suspect medicinal product, an identifiable reporting source, and an event or outcome that can be identified as serious and unexpected and for which, in clinical investigation cases, there is a reasonable suspected causal relationship. The G-CanadaCTApps requires the sponsor to complete the expedited reporting form ( CAN-5 ) and the CIOMS Form I ( CAN-7 ) and fax them to the appropriate HC Directorate: BRDD Fax: 613-957-0364; PDD Fax: 613-941-2121.
Additionally, the G-DSUR indicates that HC recommends that DSURs in electronic Common Technical Document (eCTD) format be submitted via the Common Electronic Submission Gateway (CESG). For information on eCTD format, refer to t he ElecSubms . For technical questions on eCTD filings, contact [email protected] as instructed in t he G-DSUR .
Interim and Annual Progress Reports
Pursuant to the CanadaFDR , the G-CanadaCTApps , CAN-22 , and the CA-ICH-GCP , investigators and sponsors share responsibility for submitting interim and annual reports on the status of a clinical trial. The investigator is required to provide annual progress reports to the institutional ethics committee (EC) and submit interim progress reports to the EC and Health Canada (HC) if there are any significant changes affecting the trial or risk to participants. The sponsor is required to submit annual reports (in the form of an updated Investigator’s Brochure (IB)) to HC. Note that per HCNotice-CA-ICH-GCP , HC-implemented International Council for Harmonisation (ICH) guidance takes precedence over other HC guidance when they are not consistent. For HC’s interpretation of the relevant provisions of the CanadaFDR , see the G-FDR-0100 .
As per the CA-ICH-GCP , the investigator should promptly provide written reports to the sponsor and the institutional EC on any changes significantly affecting the conduct of the trial, and/or increasing the risk to participants.
According to the G-TCPS2 , investigators must report new information that may affect the welfare or consent of participants to the institutional EC, HC, and other appropriate regulatory or advisory entities. When new information is relevant to participants’ welfare, researchers must promptly inform all participants to whom the information applies (including former participants). Researchers should work with their ECs to determine which participants must be informed, and how the information should be conveyed. New information may comprise a range of issues, including, but not limited to:
Pursuant to the CA-ICH-GCP , the investigator should submit written summaries of the trial status to the institutional EC annually, or more frequently, if requested.
Final Report
Upon completion of the trial, as delineated in CA-ICH-GCP , the investigator is required to submit a final report to the institutional EC summarizing the trial’s outcome. The CanadaFDR does not require submission of a final study report to HC.
Per the G-CanadaCTApps , the sponsor should notify the HC Directorate when a clinical trial is completed or a clinical trial site is closed. A study is considered to be completed after the last participant globally completes the "end of study" visit as defined in the protocol. The "end of study visit" is the final visit for study-related tests and procedures, including the capture of any final potential study-related adverse events, and usually occurs after the participant has completed/discontinued study drug administration. The "end of study visit" is normally an in-person visit, but for some studies it can also be carried out over the telephone. There may be certain scenarios (e.g., gene therapies, drugs with very long half-lives) where a study may be considered to be ongoing well beyond the period of study treatment, i.e., where long-term safety monitoring and reporting would be required. The reporting requirements with regards to such long-term follow-up of safety are normally specified in the study protocol and agreed to between the sponsor and HC prior to the authorization of the clinical trial in Canada.
As per the CanadaFDR and the G-CanadaCTApps , a sponsor is defined as an individual, corporate body, institution, or organization that conducts a clinical trial. The CA-ICH-GCP expands on this definition to include individuals, companies, institutions, or organizations that take responsibility for the initiation, management, and/or financing of a clinical trial.
In accordance with the CA-ICH-GCP , Canada also permits a sponsor to transfer any or all of its trial-related duties and functions to a contract research organization (CRO) and/or institutional site(s). However, the ultimate responsibility for the trial data’s quality and integrity always resides with the sponsor. Any trial-related responsibilities transferred to a CRO should be specified in a written agreement. The CRO should implement quality assurance and quality control. Note that per HCNotice-CA-ICH-GCP , Health Canada (HC) -implemented International Council for Harmonisation (ICH) guidance takes precedence over other HC guidance when they are not consistent.
According to the CanadaFDR and G-CanadaCTApps , a sponsor may be domestic or foreign. A foreign sponsor is required to have a senior medical or scientific officer who is residing in Canada who will represent the sponsor, and sign and date the application and the clinical trial attestation form.
For HC’s interpretation of the relevant provisions of the CanadaFDR , see the G-FDR-0100 .
As set forth in the CA-ICH-GCP , the sponsor should select the investigator(s) and the institution(s) for the clinical trial, taking into account the appropriateness and availability of the study site and facilities. The sponsor must also ensure that the investigator(s) are qualified by training and experience. Furthermore, the sponsor must sign an agreement or contract with the participating institution(s). Note that per HCNotice-CA-ICH-GCP , Health Canada (HC) -implemented International Council for Harmonisation (ICH) guidance takes precedence over other HC guidance when they are not consistent.
In accordance with the G-CanadaCTApps , prior to initiating a clinical trial, the sponsor must ensure that a Qualified Investigator Undertaking (QIU) form ( CAN-37 ) (or similar documentation that meets the CanadaFDR requirements) has been completed and kept on file by the sponsor; it should be retained by the sponsor for 15 years. Per the CanadaFDR , the form certifies that the qualified investigator will conduct the clinical trial in accordance with good clinical practice, and will immediately inform trial participants and the institutional ethics committee (EC) (known as Research Ethics Boards in Canada) of trial discontinuance, and the reason for this discontinuance. (See the Submission Content section for additional information on clinical trial application requirements). For HC’s interpretation of the relevant provisions of the CanadaFDR , see the G-FDR-0100 .
Per CAN-11 , the Canadian Clinical Trials Asset Map (CCTAM) ( CAN-26 ) is a pan-Canadian research inventory of investigators, clinical research sites, and other resources across the country. Sponsors can use CCTAM to identify potential sites and investigators, which may expedite study feasibility and start-up timelines. To view the CCTAM, the user must register and create an account.
Foreign Sponsor Responsibilities
According to the CanadaFDR and the G-CanadaCTApps , a sponsor may be domestic or foreign. A foreign sponsor is required to have a senior medical or scientific officer residing in Canada to represent the sponsor, and sign and date the application and the clinical trial attestation form.
Data and Safety Monitoring Board
Although not specified as a sponsor requirement, the CA-ICH-GCP states that a Data and Safety Monitoring Board (DSMB) (known as an Independent Data-Monitoring Committee in Canada) may be established to assess the progress of a clinical trial, including the safety data and the critical efficacy endpoints at intervals, and to recommend to the sponsor whether to continue, modify, or stop a trial.
The G-TCPS2 provides the following considerations to help researchers and ECs determine whether a DSMB is needed:
Multicenter Studies
Per the CA-ICH-GCP , if a multicenter trial will be conducted, the sponsor must organize a coordinating committee or select coordinating investigators. In addition, the sponsor must ensure that:
The CanadaFDR and the G-CanadaCTApps , require the sponsor to complete and retain the Research Ethics Board (REB) Attestation ( CAN-8 ) and Qualified Investigator Undertaking (QIU) ( CAN-37 ) forms at each trial site, while submitting in electronic format the Clinical Trial Site Information Form ( CAN-6 ) to the appropriate HC Directorate for each trial site.
The G-TCPS2 , which sets the ethical benchmark for all Canadian institutional ECs, provides that in multi-site clinical trials, a lead principal investigator (PI) is a designated PI who is responsible for the ethical conduct of the study for all sites. The lead PI is responsible for communicating any changes to the study, new information, and/or unanticipated events to the EC, to the sponsor, and to local site PIs.
Per HCNotice-ICH-E17 , HC announced the implementation of CAN-40 , which describes general principles for the planning and design of multi-regional clinical trials with the aim of increasing the acceptability of these trials in global regulatory submissions. HC recognizes that the scope and subject matter of current HC guidance may not be entirely consistent with ICH guidance. In such circumstances, HC-implemented ICH guidance takes precedence.
The CanadaFDR does not require the sponsor to provide insurance coverage to investigators, institutions, or trial participants. However, the CA-ICH-GCP guides sponsors on providing insurance. Note that per HCNotice-CA-ICH-GCP , Health Canada (HC) -implemented International Council for Harmonisation (ICH) guidance takes precedence over other HC guidance when they are not consistent.
Compensation
Injury or Death
The Canadian regulations do not require compensation for trial participants in the event of trial-related injuries or death. However, the CA-ICH-GCP indicates that the sponsor must explain to participants the compensation and/or treatment available to them in the event of trial-related injuries. Note that per HCNotice-CA-ICH-GCP , HC-implemented ICH guidance takes precedence over other HC guidance when they are not consistent.
Trial Participation
The Canadian regulations do not require compensation for trial participation. However, as per the G-TCPS2 and the CA-ICH-GCP , the informed consent form (ICF) should contain a statement with a description of the anticipated prorated payment to the participant(s) that is reasonably expected for participation in the trial. Any compensation or incentive to participants must not be so excessive that it may unfairly influence participants or cause them to overlook important facts and risks. CAN-35 further states that the ICF should describe any compensation, incentives, or reimbursements to be paid or given to participants and how participant withdrawal will affect the offered compensation (e.g., prorated remuneration). If no compensation will be provided, this should be stated.
Quality Assurance/Quality Control
Per the CA-ICH-GCP , the sponsor should implement a system to manage quality throughout all stages of the trial process, focusing on trial activities essential to ensuring participant protection and the reliability of trial results. Per HCNotice-ICH-E8R1 , Canada implements the International Council for Harmonisation (ICH) of Technical Requirements of Pharmaceuticals for Human Use (ICH) Guidance E8(R1): General Considerations for Clinical Studies ( CAN-49 ), which provides guidance on conduct during the clinical trial. Note that per HCNotice-CA-ICH-GCP , Health Canada (HC) -implemented ICH guidance takes precedence over other HC guidance when they are not consistent.
As indicated in the CA-ICH-GCP , the quality management system should use a risk-based approach that includes:
As stated in the CanadaFDR and the CA-ICH-GCP , the sponsor is responsible for implementing and maintaining quality assurance (QA) and quality control (QC) systems with written standard operating procedures (SOPs) to ensure that trials are conducted and data generated, recorded, and reported in compliance with the protocol, the CA-ICH-GCP , and the applicable regulatory requirements. The sponsor is responsible for obtaining agreement from all involved parties to ensure direct access to all trial related sites, source data/documents, reports for monitoring and auditing purposes, and inspection by domestic and foreign regulatory authorities. QC should be applied to each stage of data handling to ensure that all data are reliable and have been correctly processed. A written agreement must be signed by both the sponsor and the investigator or any other parties involved with the clinical trial, verifying that both parties agree to the trial protocol, the monitoring and auditing practices, the SOPs, and their respective duties.
Per the HCNotice-ICH-E9 , HC adopted and implements the ICH guidance on statistical principles for clinical trials ( HC-ICH-E9 ), as well as the ICH addendum on estimands and sensitivity analysis ( CAN-39 ), which presents a framework for defining an appropriate estimand for a clinical trial and conducting sensitivity analyses.
Monitoring Requirements
As part of its QA system, the CA-ICH-GCP notes that the sponsor should ensure the trial is monitored and audited. The purpose of the audit should be to evaluate trial conduct and compliance with the protocol, SOPs, the CA-ICH-GCP , and other applicable regulatory requirements. The sponsor should appoint auditors to review the clinical trial. The sponsor should ensure that the auditors are qualified by training and experience, and the auditors’ qualifications should be documented. The sponsor must also ensure that the audit is conducted in accordance with their own SOPs and the auditor observations are documented. The sponsor should develop a systematic, prioritized, risk-based approach to monitoring clinical trials. The extent and nature of monitoring is flexible and permits varied approaches that improve effectiveness and efficiency. The sponsor may choose on-site monitoring, a combination of on-site and centralized monitoring, or, where justified, centralized monitoring. The sponsor should document the rationale for the chosen monitoring strategy (e.g., in the monitoring plan).
Per the HCNotice-ICH-E19 , HC adopted and implements ICH guidance on selective safety data collection in specific late stage pre-approval or post-approval clinical trials ( CAN-15 ). Selective safety data collection refers to the recording of certain data by investigators in case report forms. It does not affect the monitoring and clinical care of individual trial participants or documentation of their adverse events in medical records. See the HCNotice-ICH-E19 and the CAN-15 for more information.
Premature Study Termination/Suspension
The CanadaFDR and the G-CanadaCTApps state that if a trial is prematurely terminated or suspended, the sponsor should inform HC no later than 15 days after the termination or suspension. In addition, the sponsor should provide HC with the reason(s) for the termination or suspension and its impact on the proposed or ongoing clinical trials related to the drug in Canada by the sponsor. The sponsor should also promptly notify the qualified investigators of the termination or suspension and advise them in writing of any potential risks to the participants’ health. Further, the G-CanadaCTApps states that the sponsor’s notification to HC should include c onfirmation that the sale or importation of the drug to the discontinued sites has been stopped and that reasonable measures to ensure the return of all unused quantities of the drug will be taken. This notification must also be submitted for premature discontinuation of a clinical trial or clinical trial site outside Canada where there are ongoing trials with the drug in Canada.
According to the CA-ICH-GCP , if it is discovered that noncompliance significantly affects or has the potential to significantly affect participant protection or reliability of trial results, the sponsor should perform a root cause analysis and implement appropriate corrective and preventive actions. Further, the ethics committee (EC) should also be informed promptly and provided the reason(s) for the termination or suspension by the sponsor.
Electronic Data Processing System
Per the CA-ICH-GCP , when using electronic trial data handling processing systems, the sponsor must ensure and document that the electronic data processing system conforms to the sponsor’s established requirements for completeness, accuracy, reliability, and consistency of intended performance. To validate such systems, the sponsor should use a risk assessment approach that takes into consideration the system’s intended use and potential to affect human subject protection and reliability of trial results. In addition, the sponsor must maintain standard operation procedures (SOPs) that cover system setup, installation, and use. The SOPs should describe system validation and functionality testing, data collection and handling, system maintenance, system security measures, change control, data backup, recovery, contingency planning, and decommissioning. With respect to the use of these computerized systems, the responsibilities of the sponsor, investigator, and other parties should be clear, and the users should receive relevant training. Refer to the CA-ICH-GCP for additional information.
The G-FDR-0100 provides that if electronic records are generated during a clinical trial, then the electronic system must be validated to confirm that the system’s specifications meet the goals and requirements for the clinical trial. This evidence of validation should be kept for the required record retention period and available for inspection by Health Canada (HC) inspectors. See the G-FDR-0100 for additional details.
Records Management
As set forth in the CanadaFDR and the CanadaFDR1024 , the sponsor must record, handle, and store all trial-related information to allow complete and accurate reporting, interpretation, and verification. The CanadaFDR requires the sponsor to maintain all trial-related records for a period of 15 years. Per the G-FDR-0100 , sponsors may also be required to maintain records under provincial law, institutional policies, and contractual agreements with investigators, ethics committees (ECs), or others. Where it is not possible to comply with both sets of requirements, the CanadaFDR would govern and the records must be maintained for 15 years.
Pursuant to CanadaFDR1024 , the sponsor must submit requested records to HC within 48 hours if safety concerns arise. Additionally, to facilitate inspection of a site, the sponsor must submit information to HC within seven (7) days of a request. Per CAN-8 , an attestation must be completed by the EC that reviewed and approved the clinical trial. The completed attestation must be retained by the clinical trial sponsor for a period of 15 years. The attestation should not be submitted to HC unless requested.
In addition, the CA-ICH-GCP states that the sponsor and investigator/institution should maintain a record of the location(s) of their respective essential documents including source documents. The storage system used during the trial and for archiving (irrespective of the type of media used) should allow for document identification, version history, search, and retrieval. The sponsor should ensure that the investigator has control of and continuous access to the data reported to the sponsor. The investigator/institution should have control of all essential documents and records generated by the investigator/institution before, during, and after the trial.
Responsible Parties
The G-TCPS2 , which sets the ethical benchmark for all Canadian institutional ethics committees (ECs), states that where researchers seek to collect, use, share, and access different types of information or data about participants, they should determine whether the information or data proposed in research may reasonably be expected to identify an individual. Researchers and ECs must consider whether information is identifiable or non-identifiable.
Data Protection
Per CAN-42 , the Office of the Privacy Commissioner of Canada provides advice and information for individuals about protecting personal information, and enforces the two (2) federal privacy laws that set out the rules for how federal government institutions and certain businesses must handle personal information, including health data. The PrivAct covers the personal information-handling practices of federal government departments and agencies in Canada, and the PIPEDA regulates private businesses’ data protection practices. In addition, some provinces and territories have laws that deal specifically with protection of personal health information. See CAN-43 for a list of provincial and territorial privacy laws and webpages.
Per the G-TCPS2 , in the research context, the most simplified method to protect participants is through the collection and use of anonymous or anonymized data. When anonymized data is not possible or desirable, a next best alternative is to use de-identified data, which is provided to the researcher in de-identified form and the existing key code is accessible only to a custodian or trusted third party who is independent of the researcher. Where it is not feasible to use anonymous or anonymized data for research, the ethical duty of confidentiality and the use of appropriate measures to safeguard information become paramount. Researchers should consult their ECs if they are uncertain about whether information proposed for use in research is identifiable (e.g., when proposing to link anonymized or coded data sets).
Consent for Processing Personal Data
Both PIPEDA and the PrivAct require consent for the use of personal data, including health data, except under prescribed conditions, such as for research or during emergencies. Also see CAN-43 for provincial and territorial privacy laws.
Obtaining Consent
In all Canadian clinical trials, a freely given informed consent is required from each participant in accordance with the requirements set forth in the CanadaFDR , the G-TCPS2 , the CA-ICH-GCP , and CAN-35 . Note that per HCNotice-CA-ICH-GCP , Health Canada (HC) -implemented International Council for Harmonisation (ICH) guidance takes precedence over other HC guidance when they are not consistent. For HC’s interpretation of the relevant provisions of the CanadaFDR , see the G-FDR-0100 .
As per the CanadaFDR , the G-TCPS2 , and the CA-ICH-GCP , the informed consent form (ICF) is viewed as an essential document that must be reviewed and approved by an institutional ethics committee (EC) (known as a Research Ethics Board (REB) in Canada) and provided to HC with the clinical trial application (CTA). (See the Required Elements section for details on what should be included in the form.)
The G-TCPS2 and the CA-ICH-GCP state that the qualified investigator (QI) must provide detailed research study information to the participant or legal representative/guardian. As delineated in the G-TCPS2 , CAN-35 , and the CA-ICH-GCP , the ICF content should be in plain language (i.e., non-technical and easy to understand) and provided in a format that facilitates understanding. For example, written documentation may be supplemented with audio and/or visual aids. The participant and legal representative/guardian should also be given adequate time to consider whether to participate. CAN-35 notes that the person obtaining consent may also need to explain the consent form verbally to ensure that the participant fully understands the information. See CAN-35 for informed consent and assent templates and sample forms.
According to the CA-ICH-GCP , any change in the ICF that is relevant to the participant’s consent should be approved by the institutional EC prior to implementing any changes. The participant or legal representative/guardian should also be informed in a timely manner if new information becomes available that may be relevant to the participant’s willingness to continue participation in the trial. The communication of this information should be documented.
Per the G-TCPS2 , consent must be maintained throughout the research project. Researchers have a continuous duty to provide participants with all information relevant to their ongoing consent to participate in the research. Consent begins with the initial contact (e.g., recruitment) and carries through to the end of participation in the study. Throughout the clinical trial, researchers have a continuous responsibility to provide participants and ECs with all information relevant to participants’ ongoing consent to participate in the research. The researcher also must notify participants of any changes to the research project that may affect them. These changes may have ethical implications, may be relevant to their decision to continue in the study, or may be unique to the particular circumstances of individual participants. Specifically, researchers must disclose changes to the risks or potential benefits of the research. Change in participant capacity is an important element of ongoing consent. Rather than an age-based approach to consent, researchers should use an approach based on decision-making capacity in compliance with any laws governing research participation. This includes those whose decision-making capacity is in the process of development, those whose decision-making capacity is diminishing or fluctuating, and those whose decision-making capacity remains only partially developed. Mechanisms should be in place from the outset to identify and address any changes that could affect consent. Further, within the limits of consent provided by the participant, researchers should disclose to the participant any material incidental findings discovered in the course of research. Incidental findings are considered to be material incidental findings if they are reasonably determined to have significant welfare implications for the participant or prospective participant. Where material incidental findings are foreseeable, researchers should inform participants during the initial consent process. In addition, researchers should develop a management plan for review by the EC. For more information on how to address material incidental findings, see G-ConsentMatIncFindings .
Language Requirements
CAN-35 further specifies that consent forms should be provided in the language that participants are most comfortable with. The G-TCPS2 and the CA-ICH-GCP require the ICF to be presented in plain language that the participant is able to understand. Per CAN-35 , ICFs should be translated where it is relevant to particular communities. If there is a language barrier, the G-TCPS2 indicates that the qualified investigator should select an intermediary who has the necessary language skills to ensure effective communication. Further, per CAN-35 , the level of language used should be appropriate to the age and comprehension/reading level of the participant population, generally at approximately a grade 6-8 reading level.
Documenting Consent
As per the G-TCPS2 , the CA-ICH-GCP , and CAN-35 , the participant or legal representative/guardian, as well as the qualified investigator, must sign and date the ICF. The CA-ICH-GCP and the G-FDR-0100 state that the QI should retain the signed ICF. CAN-35 indicates that information letters and ICFs must be presented on institutional/department letterhead.
According to the CA-ICH-GCP , where the participant is illiterate and/or the legal representative/guardian is illiterate, an impartial witness should be present during the entire informed consent discussion. The witness should sign and date the ICF after the following steps have occurred:
Before participating in the study, the participant or legal representative/guardian should receive a copy of the signed and dated ICF.
As per the G-TCPS2 and the CA-ICH-GCP , none of the oral and written information concerning the research study, including the written ICF, should contain any language that causes the participant or legal representative/guardian to waive or appear to waive the participant’s legal rights, or that releases or appears to release the investigator(s), the institution, the sponsor, or their representative(s) from their liabilities for any negligence.
Per CAN-35 , in some situations, written consent is not be feasible or desirable, for example due to logistical issues or because of the preferences of the participants. In addition, some individuals may perceive written consent as an attempt to legalize the consent process, thereby creating mistrust. It is also important to recognize that in some cultures written consent is not consistent with community traditions. In these cases, it may be more appropriate to use a handshake, a verbal agreement, or oral consent. Article 10.2 of the G-TCPS2 further indicates that researchers can use a range of procedures to seek and document consent, including oral consent documented in field notes, and other forms of recording (e.g., a consent log, audio or video recordings, or other electronic means). Evidence of consent may also be documented via completed questionnaires (in person, by mail, or by email or other electronic means). ECs should consider the power relationship that might exist between researchers and participants, and whether a waiver of the requirement for signed written consent may affect the welfare of the participants. If researchers plan to obtain non-written consent, they must explain their strategy to the EC.
Waiver of Consent
As explained in the G-TCPS2 , there are research situations that call for alterations of consent. The EC may approve research that involves an alteration to the consent requirements if the EC is satisfied, and documents, that all of the following apply:
Based on the G-TCPS2 , the CA-ICH-GCP , and CAN-35 , the informed consent form (ICF) should include the following statements or descriptions in plain language, as applicable (Note: Each of the items listed below will not necessarily be found in all sources, which provide overlapping and unique elements):
Per CAN-35 , if blood is taken, indicate total volume (e.g., teaspoons and milliliter equivalent) and note the possibility of bruising or swelling while giving blood, or other possible discomforts at the site where blood is drawn. Further, state that there may be minimal chance of infection and that discomforts experienced will be brief and transient.
CAN-35 also indicates that participants should not be told if an EC has approved the study, since this may appear to offer a guarantee of safety. Further, no clause or language should be used to excuse or appear to excuse investigators or other persons or institutions involved from liability for their negligence or other faults. Sample consent forms can be found in CAN-35 .
See the Vulnerable Populations and Consent for Specimen sections for further information.
In accordance with the CanadaFDR , the G-TCPS2 , and the CA-ICH-GCP , Canada’s ethical standards promote respect for all human beings and safeguard the rights of research participants. The G-TCPS2 and the CA-ICH-GCP state that a participant’s rights must also be clearly addressed in the informed consent form (ICF) and during the informed consent process. Note that per HCNotice-CA-ICH-GCP , Health Canada (HC) -implemented International Council for Harmonisation (ICH) guidance takes precedence over other HC guidance when they are not consistent. For HC’s interpretation of the relevant provisions of the CanadaFDR , see the G-FDR-0100 .
The informed consent template in CAN-35 provides that if a participant has any questions about their rights, they should contact:
Health Canada-PHAC Research Ethics Board Secretariat 70 Colombine Driveway, Room 941C, PL: 0909C Brooke Claxton Building, Tunney's Pasture Ottawa, ON K1A 0K9 Telephone: 613-941-5199 Fax: 613-941-9093 [email protected]
The Right to Participate, Abstain, or Withdraw
As stated in the G-TCPS2 and the CA-ICH-GCP , the participant or legal representative/guardian should be informed that participation is voluntary, that they may withdraw from the research study at any time, and that refusal to participate will not involve any penalty or loss of benefits to which the participant is otherwise entitled.
Per CAN-35 , participants should be assured that their participation is completely voluntary, they are under no obligation to participate, and they are free to withdraw at any time without consequence. It should be made clear that their decision to withdraw will not influence their relationship with the researcher in any way. The researcher should explain what will happen to participant samples or data if they choose to withdraw. If applicable, clearly state the point in the study at which removal of samples or data becomes difficult or impossible.
The Right to Information
As per the G-TCPS2 and the CA-ICH-GCP , a potential research participant or legal representative/guardian has the right to be informed about the nature and purpose of the research study, its anticipated duration, study procedures, any potential benefits or risks, any compensation or treatment in the case of injury, and any significant new information regarding the research study.
The Right to Privacy and Confidentiality
According to the G-TCPS2 and the CA-ICH-GCP , all participants must be afforded the right to privacy and confidentiality, and the ICF must provide a statement that recognizes this right.
Per CAN-35 , the ICF should explain what information will be collected about participants and for what purpose, including the type of information that will be collected (e.g., will it be coded or de-identified?) and how it will be stored. Further, the ICF should state who will have access to the collected information and describe the efforts that will be made to prevent the risk of participant re-identification. Limits to confidentiality and additional requirements for projects led by HC or the Public Health Agency of Canada (PHAC) are provided in CAN-35 .
The Right of Inquiry/Appeal
The G-TCPS2 and the CA-ICH-GCP state that the research participant or legal representative/guardian should be provided with contact information for the individual responsible for addressing trial-related inquiries and/or the participant’s rights.
The Right to Safety and Welfare
The CA-ICH-GCP , which upholds the Declaration of Helsinki, clearly state that a research participant’s right to safety and the protection of their health and welfare must take precedence over the interests of science and society.
See the Required Elements and Vulnerable Populations sections for additional information regarding requirements for participant rights.
The G-TCPS2 and the CA-ICH-GCP make provisions to protect the rights of a research participant during the informed consent process when the procedure is complicated by medical emergencies. Note that per HCNotice-CA-ICH-GCP , Health Canada (HC) -implemented International Council for Harmonisation (ICH) guidance takes precedence over other HC guidance when they are not consistent. As per the CA-ICH-GCP , in an emergency, if the signed informed consent form (ICF) has not been obtained from the research participant or legal representative/guardian, or, if an effective treatment is lacking but the investigational product could address the participant’s emergency needs, the clinical trial may be conducted. However, the method used on the participant must be explained clearly in the trial protocol, and the ethics committee (EC) (known as Research Ethics Board (REB) in Canada) must approve the protocol in advance. The participant or legal representative/guardian should be informed about the trial as soon as possible, and consent to continue and other consent should be requested, as appropriate.
Per G-TCPS2 , research involving medical emergencies must be conducted only if it addresses the emergency needs of the individuals involved, and then only in accordance with criteria established in advance of such research by the EC. The EC may allow research that involves medical emergencies to be carried out without the consent of participants, or legal representatives/guardians, if all of the following apply:
As per the G-TCPS2 , in all Canadian clinical trials, research participants selected from vulnerable populations must be provided additional protections to safeguard their health and welfare during the informed consent process. The CA-ICH-GCP characterizes vulnerable populations as those who may be unduly influenced by the expectation, whether justified or not, of benefits associated with participation, or of a retaliatory response from not participating. Examples are members of a group with a hierarchical structure, such as medical, pharmacy, dental, and nursing students; subordinate hospital and laboratory personnel; employees of the pharmaceutical industry; members of the armed forces; and persons kept in detention. Other vulnerable subjects include patients with incurable diseases, persons in nursing homes, unemployed or impoverished persons, patients in emergency situations, ethnic minority groups, homeless persons, nomads, refugees, minors, and those incapable of giving consent.
The CA-ICH-GCP specify that ethics committees (ECs) (known as Research Ethics Boards in Canada) must pay special attention to protecting participants who are from vulnerable populations. Note that per HCNotice-CA-ICH-GCP , Health Canada (HC) -implemented International Council for Harmonisation (ICH) guidance takes precedence over other HC guidance when they are not consistent.
See the Children/Minors; Pregnant Women, Fetuses & Neonates; and Mentally Impaired sections for additional information about these vulnerable populations.
Per CAN-35 , because the G-TCPS2 does not specify an age of consent for children, the decision on whether to seek consent from children is based on whether they have the capacity to understand the research and the risks and benefits of their participation. Youth who have not reached the age of majority (either 18 or 19 depending on the province or territory) may still be old enough to provide their own consent. For children who are not sufficiently mature to provide consent but are able to understand the nature of study participation, researchers must obtain the child’s assent in addition to the consent of an authorized third party. The decision of a child not to assent must be respected regardless of whether third-party consent was obtained.
CAN-35 provides the following criteria for determining whether participants can provide their own consent, or whether an authorized third party should be involved:
CAN-35 states that it is generally accepted that youth can consent to minimal risk studies at 16 years of age, and that assent should be sought from children beginning at approximately seven (7) years of age. However, it is ultimately up to the researcher to determine whether to obtain assent or consent from children, and to provide the rationale for this decision to the ethics committee (EC) (known as a Research Ethics Board in Canada). Researchers should also consider that within a single research project, some minors may be capable of consenting while others may not. See CAN-35 for additional details regarding obtaining consent from minors.
As per the G-TCPS2 and the CA-ICH-GCP , when the research participant is a child, the informed consent form (ICF) must be signed by the child’s parent/legal guardian. All pediatric participants, however, should be informed to the extent compatible with the child’s understanding, and if capable, the pediatric participant should sign and personally date the ICF. Note that per HCNotice-CA-ICH-GCP , Health Canada (HC) -implemented International Council for Harmonisation (ICH) guidance takes precedence over other HC guidance when they are not consistent.
As stated in G-TCPS2 , children should only participate in clinical studies when the research objective cannot be achieved with adult participants only. When considering the inclusion of children in research, the investigators and ECs must consider a child’s stage of physical, physiological, psychological, and social development to ensure adequate protections for the child’s welfare.
Assent Requirements
Per G-TCPS2 and TCPS2-InterpCnsnt , where a child has some ability to understand the significance of the research, the researcher must ascertain the wishes of that individual with respect to participation. Children—whose decision-making capacity is in the process of development—may be capable of verbally or physically assenting to, or dissenting from, participation in research. While their assent would not be sufficient to permit them to participate in the absence of consent by the child’s parent/legal guardian, their expression of dissent must be respected.
Further, according to CAN-12 , which offers best practices and guidance to researchers and ECs in pediatric research and complements the G-TCPS2 , provincial laws in Canada vary as to when a child is presumed to be legally competent to provide informed consent. Some provinces use age while others use a competence-based evaluation.
As per CAN-12 , if the pediatric participant has the capacity for assent, then affirmative assent is required to participate in a study according to the participant’s level of development and capacities. When the child develops the legal capacity to provide informed consent or attains the legal age of majority (which depends on the province), researchers should obtain an informed consent. Regarding dissent, CAN-12 states that the researchers must respect the dissent of a child who is capable of understanding.
CAN-35 provides sample assent forms and templates. For more detail and guidance about best practices for research involving pediatric participants, see CAN-12 .
As per the G-TCPS2 , studies involving women of childbearing age, or who are pregnant, require additional safeguards to ensure that the research assesses the risks to the women and the fetuses. The following guidance applies to research involving materials related to human reproduction:
Per the G-TCPS2 , research on in vitro embryos already created and intended for implantation to achieve pregnancy is acceptable if:
According to the G-TCPS2 , research involving embryos that have been created for reproductive or other purposes permitted by law, but are no longer required for these purposes, may be ethically acceptable if:
Per the G-TCPS2 , research involving a fetus or fetal tissue:
In accordance with the CA-ICH-GCP , informed consent requirements for conducting clinical trials with pregnant or nursing women or fetuses follow the general requirements listed in the Required Elements section . Specifically, the informed consent form should include a statement on the reasonably foreseeable risks or inconveniences to the participant, and when applicable, to an embryo, fetus, or nursing infant. Note that per HCNotice-CA-ICH-GCP , Health Canada (HC) -implemented International Council for Harmonisation (ICH) guidance takes precedence over other HC guidance when they are not consistent.
According to the G-TCPS2 and the CA-ICH-GCP , prisoners are considered vulnerable because incarceration could affect their ability to make a voluntary decision regarding participation in research. A research study involving prisoners should ensure that these prospective participants are informed and are given the opportunity to make their own decisions without any interference from a higher authority. Note that per HCNotice-CA-ICH-GCP , Health Canada (HC) -implemented International Council for Harmonisation (ICH) guidance takes precedence over other HC guidance when they are not consistent.
According to the G-TCPS2 and the CA-ICH-GCP , the ethics committee (EC) (known as Research Ethics Board in Canada) must approve the participation of research participants who are mentally or physically incapable of giving consent.
Per CAN-35 , adults with diminished decision-making capacity include:
Per CAN-35 , as is the case for any vulnerable population, care must be taken to ensure that adults with diminished decision-making capacity are not inappropriately included in research because of their situation, and neither should they be excluded from participating in research that may benefit them.
The G-TCPS2 indicates that for research involving individuals who lack the capacity, either permanently or temporarily, to decide for themselves whether to participate, the EC must ensure that, at a minimum, the following conditions are met:
Per CAN-35 and the G-TCPS2 , the participant’s legal representative/guardian can provide consent for adults who lack the capacity to decide on their own behalf in accordance with the best interests of the persons concerned. In such cases, participants should still be involved to the greatest extent possible in the decision-making process, and their assent to participate must be obtained if they are capable of expressing their wishes in a meaningful way (whether verbally or physically). Importantly, when authorization for participation was granted by the participant’s legal representative/guardian and a participant acquires or regains decision-making capacity during the course of the research, the researcher must promptly seek the participant’s consent as a condition of continuing participation.
Note that per HCNotice-CA-ICH-GCP , Health Canada (HC) -implemented International Council for Harmonisation (ICH) guidance takes precedence over other HC guidance when they are not consistent.
As delineated in the CanadaFDR , the G-GMP-Annex13 , and the CA-ICH-GCP , an investigational product is defined as a pharmaceutical form of an active ingredient or placebo being tested or used as a reference in a clinical trial, including a product with a marketing authorization when used or assembled (formulated or packaged) in a way different from the approved form. Note that per HCNotice-CA-ICH-GCP , Health Canada (HC) -implemented International Council for Harmonisation (ICH) guidance takes precedence over other HC guidance when they are not consistent.
Manufacturing
As specified in the CanadaFDR , the G-CanadaCTApps , and the CA-ICH-GCP , Health Canada (HC) authorizes the manufacture of investigational products (IPs) in Canada. HC approves the manufacture of IPs as part of the clinical trial application (CTA) approval. Note that per HCNotice-CA-ICH-GCP , HC-implemented International Council for Harmonisation (ICH) guidance takes precedence over other HC guidance when they are not consistent. The G-QCM-PharmCTAs provides guidance and templates to assist sponsors in completing the quality portion of the CTA, which in turn, enables HC to assess IP characteristics adequately. The G-GMP-Annex13 requires the sponsor to ensure that IPs for clinical trials are manufactured and imported in accordance with its provisions and with CanadaFDR requirements. Per the G-CanadaCTApps , sponsors must file amendments or notifications to a previously authorized CTA when manufacturing changes are proposed that may affect the quality or safety of the clinical trial drug or biologic supplies.
Per the CanadaFDR and the G-FDR-0100 , HC authorizes the sponsor to import an IP. A sponsor who is not based in Canada must have a Canadian representative who is responsible for the import of the IP and demonstrates compliance with the applicable regulatory requirements. This representative should be the sponsor’s senior medical or scientific officer residing in Canada and is responsible for providing an attestation with respect to the CTA at the time of filing. Per the G-CanadaCTApps , the G-DrugApp , and CAN-4 , if clinical trial drugs are to be imported into Canada, the authorization template (Appendix 1) in CAN-4 should be completed and submitted for each importer in Canada. The G-DrugApp states that Canadian importer(s) must be located within Canada. As additional importers are identified, additional copies of the authorization template in CAN-4 should be provided to HC. The G-FDR-0100 , provides additional guidance on requirements if a sponsor plans to send the clinical trial IP(s) directly to each trial site:
The G-CanadaCTApps , the G-HlthProdImprtExptReqs , the G-FDR-0100 , and CAN-32 state that if a sponsor wants to import a drug into Canada for a clinical trial, a copy of HC’s authorization (i.e., the No Objection Letter (NOL)) issued by either the Pharmaceutical Drugs Directorate (PDD) or the Biologic and Radiopharmaceutical Drugs Directorate (BRDD) must be included for the applicable trial with the shipment. A copy of this authorization must be provided at the port of entry. The G-HlthProdImprtExptReqs states that drugs without a Drug Identification Number may be imported where authorized for a Canadian clinical trial and a NOL was issued. The G-FDR-0100 further states that if 30 days have passed and the NOL was not issued, specific requests to import IPs should be directed to the Health Product Border Compliance Program at the following email account: [email protected] . Note that a sponsor does not have to submit a CTA for authorization to import an IP used in a Phase IV clinical trial.
Per CanadaFDR , the sponsor can make the following changes to the authorized use or importation of drugs if the sponsor notifies HC in writing within 15 days after the date of the change:
Other changes must follow the amendment requirements delineated in the CanadaFDR . See the G-FDR-0100 for additional HC interpretations of the relevant provisions of the CanadaFDR .
Investigator’s Brochure
In accordance with the CanadaFDR and the CA-ICH-GCP , the sponsor is responsible for providing the investigators with an Investigator’s Brochure (IB). The CanadaFDR and the CA-ICH-GCP specify that the IB must contain all of the relevant information on the investigational product(s) (IPs), including significant physical, chemical, pharmaceutical, pharmacological, toxicological, pharmacokinetic, metabolic, and clinical information. The sponsor must ensure that an up-to-date IB is made available to the investigator(s), and the investigator(s) must provide an up-to-date IB to the ethics committee. Note that per HCNotice-CA-ICH-GCP , Health Canada (HC) -implemented International Council for Harmonisation (ICH) guidance takes precedence over other HC guidance when they are not consistent. For HC’s interpretation of the relevant provisions of the CanadaFDR , see the G-FDR-0100 .
The CanadaFDR and the CA-ICH-GCP require the IB to provide coverage of the following areas:
See Section 7.3 of the CA-ICH-GCP for detailed content guidelines.
In accordance with the G-CanadaCTApps and CAN-22 , the sponsor must submit annually to HC an updated IB, which serves as the annual report, including all safety information and global status. Revisions that are more frequent may be appropriate depending on the stage of development and the generation of relevant new information.
Quality Management
Pursuant to the CA-ICH-GCP , the sponsor must maintain a Certificate of Analysis to document the identity, purity, and strength of the IP(s) to be used in the clinical trial. As specified in the CA-ICH-GCP , G-GMP-CAN , and G-GMP-Annex13 , the sponsor must ensure that the products are manufactured in accordance with Good Manufacturing Practice (GMP). The G-GMP-CAN requires a quality management system, incorporating GMP, to ensure that IPs are of the quality required for their intended use. Per the G-GMP-Annex13 , the manufacturer’s quality system should be described in written procedures and available to the sponsor, taking into account GMP principles and guidelines.
Investigational product (IP) labeling in Canada must comply with the requirements set forth in the CanadaFDR , the G-CanadaCTApps , the G-GMP-Annex13 , and the CA-ICH-GCP . The CanadaFDR and the G-CanadaCTApps state that for an IP to be used in a clinical trial, it must be properly labeled in both official languages: English and French. The CanadaFDR requires that IPs be packaged and labelled under the supervision of personnel who have had satisfactory technical, academic, and other training. The packager and/or labeler must have written procedures and ensure that the IP is packaged, labelled, and tested in compliance with those procedures. For Health Canada (HC) ’s interpretation of the relevant provisions of the CanadaFDR , see the G-FDR-0100 .
As delineated in the CanadaFDR and the G-GMP-Annex13 , the following information must be included on the IP label:
With regard to the expiration date, the G-GMP-Annex13 further states that if it becomes necessary to change the expiration date, an additional label should be affixed to the IP. This additional label should state the new expiration date and repeat the batch number. It may be superimposed on the previous expiration date, but for quality control reasons, not on the original batch number. This operation should be performed at an appropriately authorized manufacturing site. However, when justified, it may be performed at the investigational site by or under the supervision of the clinical trial site pharmacist, or other health care professional in accordance with national regulations and with the sponsor’s requirements. Where this is not possible, it may be performed by the clinical trial monitor(s) who should be appropriately trained. The operation should be performed in accordance with good manufacturing practice (GMP) principles, specific and standard operating procedures and under contract, if applicable, and should be checked by a second person. This additional labelling should be properly documented in both the trial documentation and in the packaging records.
In addition, the CA-ICH-GCP state that the IP must be coded and labeled in a manner that protects the blinding, if applicable.
Supply, Storage, and Handling Requirements
Per CanadaFDR , drugs must be manufactured, handled, and stored in accordance with good manufacturing practice (GMP). As defined in the CA-ICH-GCP , the sponsor must supply the investigator(s) with the investigational products (IP(s)), including the comparator and placebo, if applicable. The sponsor should not supply the IP(s) until approvals from Health Canada (HC) and the institutional ethics committee (EC) are obtained. The CA-ICH-GCP specify that the sponsor must ensure the following:
For IP packaging, the G-GMP-Annex13 provides the following guidance:
The G-Storage provides principles and interpretations on the environmental control of clinical trial drugs during storage and transportation, including packaging. See G-Storage for information regarding compliance with the CanadaFDA and the CanadaFDR , as it relates to packaging clinical trial drugs for human use, such as the role of environmental controls, quality risk management, and special considerations for active pharmaceutical ingredients. In addition, the CA-ICH-GCP state that the IP must be packaged in a manner that will prevent contamination and unacceptable deterioration during transport and storage. Refer to the CA-ICH-GCP for detailed sponsor-related IP requirements.
Record Requirements
As set forth in the CanadaFDR , the G-FDR-0100 , and the CanadaFDR1024 , the sponsor must record, handle, and store all trial-related information to allow complete and accurate reporting, interpretation, and verification. The CanadaFDR states that the sponsor should maintain all trial-related records for a period of 15 years. Pursuant to CanadaFDR1024 , the sponsor must submit requested records to HC within 48 hours if safety concerns arise. Additionally, to facilitate inspection of a site, the sponsor must submit information to HC within seven (7) days of a request.
The G-Storage provides that when contracted parties, such as warehouses or commercial carriers, store or transport drugs, there should be a written agreement that outlines all relevant conditions.
In Canada, a specimen is referred to as “human biological material” or “biological material.” According to the G-TCPS2 , human biological materials include tissues, organs, blood, plasma, skin, serum, DNA, RNA, proteins, cells, hair, nail clippings, urine, saliva, and other body fluids. The term also comprises materials related to human reproduction, including embryos, fetuses, fetal tissues, and human reproductive materials. The G-TCPS2 breaks down human biological material further into the following categories: anonymized, anonymous, coded, and identified human biological materials. Refer to the G-TCPS2 for more detailed information on these categories.
In addition, CAN-2 defines biological material as pathogenic and non-pathogenic microorganisms, proteins, and nucleic acids, as well as any biological matter that may contain microorganisms, proteins, nucleic acids, or parts thereof. Examples include, but are not limited to, bacteria, viruses, fungi, prions, toxins, genetically modified organisms, nucleic acids, tissue samples, diagnostic specimens, live vaccines, and isolates of a pathogen (e.g., pure culture, suspension, purified spores).
Import/Export
According to the G-HlthProdImprtExptReqs , Health Canada (HC) does not have jurisdiction over human biological materials to be imported for testing or research purposes. The G-HlthProdImprtExptReqs further states that all blood samples as well as cultures, diagnostic specimens, or research tissue are considered to be potential carriers of human or animal pathogens, and are regulated by the Public Health Agency of Canada (PHAC) and the Canadian Food Inspection Agency (CFIA) . Per CAN-24 , CAN-2 , and CAN-9 , the PHAC’s Centre for Biosecurity oversees the licensing process under the authority of the HPTA and the HPTR . The HPTA states that a license must be issued by the Minister that authorizes the import or export of human pathogens or toxins.
As specified in the HPTA , the HPTR , and CAN-2 , individuals planning to conduct controlled activities (including producing, possessing, handling, using, storing, providing access to, transferring, disposing of, releasing, abandoning, or importing/exporting) with a human pathogen or toxin, whether imported or domestically acquired, must obtain a license. Per CAN-2 , because all human biological materials are potential carriers of human pathogens, the PHAC has categorized these materials by risk group based on risk to the individual/animal and risk to the community. Risk Group 1 consists of microorganisms, nucleic acids, or proteins that are unable or unlikely to cause human or animal disease so they are generally not considered to be pathogens, and are therefore exempt from the HPTA and the HPTR licensing requirements. Risk groups 2 through 4 are considered to be pathogens or toxins with moderate to high individual risk and low to high community risk, and are subject to the HPTA and the HPTR licensing requirements. See CAN-2 and CAN-9 for detailed information and instructions on how to obtain a license for activities associated with Risk Groups 2 through 4.
In accordance with the G-TCPS2 , prior to collecting, storing, or using a research participant’s biological specimen(s), consent from the participant and/or the legal representative(s) and review/approval from the institutional ethics committee (EC) (known as Research Ethics Board (REB) in Canada) must be obtained. Specifically, consent is required from the following:
In addition, the G-TCPS2 states that in order to seek participant consent to use the participant’s biological materials in research, the investigator(s) must provide the prospective participant or authorized third party with the following information:
Per CAN-35 , if there is a possibility of secondary future use of biological materials, researchers should consider describing this possibility in the consent form and obtaining permission from participants to retain their data or biological materials for future use. If consent for future use is not obtained initially then researchers may be required to obtain re-consent from individuals in the future. Researchers should be as specific as possible when describing the potential future uses. For example, if future uses include possible genetic or genomic studies, this must be stated. The EC may not approve future uses that are too open-ended or too dissimilar from the initial use. It is generally preferable to give participants the opportunity to opt out of future use. If this option is not provided, researchers should be prepared to explain their decision to the EC. When seeking consent, researchers may wish to give participants different options for how their samples or data can be used, to accommodate differences in comfort levels among participants. In rare cases, it may be possible to use identifiable information for secondary use without the consent of the participants who provided that information. While the possibility of an exception may exist, the EC generally expects that researchers will make every reasonable effort to seek the consent of participants. Thus, the best practice is for researchers to always obtain consent for future use at the time of initial recruitment if there is any possibility of secondary use of data or biological materials. Also see the G-TCPS2 and the TCPS2-InterpCnsnt for additional details on confidentiality, future use of information, broad consent for the storage of data and human biological materials for future unspecified research, biobanks, and stem cell consent.
Uottawa rebs.
The mandate of the REBs is to assess and sanction the ethical aspects of all research projects involving human participants conducted under their jurisdiction by their professors and students, prior to their inception and during their execution. The REBs also verify how researchers plan to take on their ethical responsibilities. The REBs must also approve all projects in which students, professors or support staff of the University of Ottawa serve as research participants.
There are two Research Ethics Boards (REB) at the University of Ottawa.
Research projects taking place at any of the regional affiliated hospitals (recruitment or data collection) must also be reviewed by the REB of that hospital. It is generally recommended that researchers submit their applications to the hospital REB first, and once approval is obtained, submit to the uOttawa REB for expedited review. We recommend that researchers contact both REBs before beginning this process to ensure the correct steps are being followed.
Information on the affiliated hospital REBs can be found at the following links:
Ottawa Health Science Network REB
(Ottawa Hospital and Heart Institute)
Children’s Hospital of Eastern Ontario REB
Royal REB (Institute of Mental Health Research)
Bruyère Continuing Care REB
The Hôpital Montfort REB
Social sciences and humanities reb arrow_drop_down.
The University of Ottawa has signed agreements with the following affiliated hospitals and their respective REBs:
Tabaret Hall 550 Cumberland St Room 154 Ottawa, ON, Canada K1N 6N5
Tel.: 613-562-5800 ext. 5387 Fax.: 613-562-5338
[email protected]
Mathieu Laflamme Work E-mail : [email protected]
Riana Marcotte Work E-mail : [email protected]
Germain Zongo Work E-mail : [email protected]
HREBA Departmental or Site Approval Form – version April 2018
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Initial submissions
REB Application for Prospective Studies (TAHSN) (DOC)
REB Application for Retrospective Access to Health Records (DOC)
REB Application for Use of Tissue/Blood/Body Fluid (DOC)
Sample Consent Template (DOC)
Consent Form Summary (DOC)
Ongoing submissions
Amendment/Administrative Change Form (DOC)
Change in Study Personnel Form (DOC)
Annual Renewal/Termination Report Form (DOC)
Protocol Deviation Report Form (DOC )
External SAE/Unanticipated Problem Report Form (DOC)
Internal SAE/Unanticipated Problem Report Form (DOC)
Guidelines for REB Application for Prospective Studies (TAHSN) (DOC)
Guidelines for writing proposals and consent forms (DOC)
Guidelines for recruitment materials (DOC)
Guidelines for Amendments/Administrative Changes (DOC)
Guidelines on Annual Renewals (DOC)
Guidelines on Study Completion (DOC)
Guidelines for Reporting Protocol Deviations (DOC)
Guidelines for Reporting SAEs/Unanticipated Problems (DOC)
When constructing a consent form, please choose the Confidentiality section that best fits your study type:
Sponsored, Health Canada registered study (DOC) Sponsored study, not registered with Health Canada (DOC) Non-sponsored, Health Canada registered, multi-site study (DOC) Non-sponsored, Health Canada registered, MSH-only study (DOC) Non-sponsored, multi-site study, not registered with Health Canada (DOC) Non-sponsored, MSH-only study, not registered with Health Canada (DOC)
All research has ethical implications, whether it involves, humans, animals or anonymised datasets.
Research Ethics Committees (or Ethical Review Boards) help researchers consider and prepare for ethical issues that their research might raise. The main way Research Ethics Committees do this is by reviewing a researcher’s ethics application for their project.
Research Ethics Committee approval of an ethics application is usually a requirement in order to conduct the research project.
The Health Research Authority`s decision tool help you decide whether or not your study is research as defined by the UK Policy Framework for Health and Social Care Research.
There are different Research Ethics Committees to review different research projects. This table will help you figure out which committees would be relevant for research conducted with St George’s.
Which Ethics Committees to Apply to | Researcher | ||||
---|---|---|---|---|---|
St George’s University London (Students) | St George’s University London (Staff) | St George’s Hospital Trust (Staff) | Other Organisation | ||
Participant or Data | St George’s University London (Students) | SGREC | SGREC | SGREC | Other Organisation’s Process + SGREC |
St George’s University London (Staff) | SGREC | SGREC | SGREC | Other Organisation’s Process + SGREC | |
St George’s University London (Animals¹) | AWERB | AWERB | AWERB | Other Organisation’s Process + AWERB | |
St George’s Hospital Trust / Other NHS Site (Staff) Recruited through NHS | SGREC + HRA | SGREC + HRA | SGREC + HRA | Other Organisation’s Process + SGREC + HRA | |
Participants not recruited through NHS | SGREC | SGREC | SGREC | - | |
St George’s Hospital Trust / Other NHS Site (Patients)² | HRA + NHS REC | HRA + NHS REC | HRA + NHS REC | Other Organisation’s Process + HRA + NHS REC | |
Other Organisation | SGREC + Other Organisation’s Process | SGREC + Other Organisation’s Process | SGREC + HRA + Other Organisation’s Process | - | |
Clinical Audits and Service Evaluations³ | SGREC | SGREC | Register with clinical audit team in relevant Trust. For St George’s email
| - |
¹ Any research requiring animals for whatever purpose, requires submission to AWERB (Animal Welfare Ethical Review Body).
² SGREC not required if being reviewed by nationally recognised research ethics committee (usually NHS REC, but would include Ministry Of Defence REC).
³ Ethical approval is not required but a SAFE and protocol should be submitted to the SGREC for review and registration.
All joint faculty students with degrees awarded by Kingston University should submit applications for a favourable ethical opinion using Kingston University Research ethics Online System KUREOS
Please note that if your research falls into more than one category, (eg involving animals and patients) then you may need additional approvals. Please contact the Research Ethics and Integrity Officer for help.
If your research project requires review by St George’s Research Ethics Committee (SGREC), please see the Standard Operating Procedure (PDF) and the following page.
Learn how to apply to the SGREC for ethical review of your project.
Find committee meeting dates, drop-in sessions, annual reports and policies.
Useful information about the sponsorship process for international research studies.
Important information about registering and submitting projects involving human tissue samples.
If you are unable to view this page please email the Research Ethics and Integrity Officer .
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An attestation must be completed by the Research Ethics Board that reviewed and approved the clinical trial protocol and informed consent form for this clinical trial at the site specified below. The completed attestation must be retained by the clinical trial sponsor for a period of 15 years. Please note that the Research Ethics Board ...
Research Ethics Board Attestation Author: Government of Canada - Health Canada Subject: Research Ethics Board Attestation Created Date: 3/7/2022 3:30:33 PM ...
Memo re: Health Canada's REB Attestation Form (REBA) (August 16, 2023) A Collaboration of. Disclaimer: The Hamilton Integrated Research Ethics Board (HiREB) represents the institutions of Hamilton Health Sciences, St. Joseph's Healthcare Hamilton, Research St. Joseph's-Hamilton, and the Faculty of Health Sciences at McMaster University and ...
REB 4: HEALTH RESEARCH ETHCIS BOARD - BIOMEDICAL PANEL. Health Canada REB Attestation Form. It is the Health Research Ethics Boards' policy not to sign individual Health Canada REB Attestation Forms. This letter serves as a substitute for this form, and is be taken into consideration along with any specific study approval that will be issued ...
This forms cabinet contains guidance documents and templates that can be used to assist with the preparation of an application. Human Participant Research Research Ethics Board (REB) 1 and 2. Guidelines for Course-based Research Involving Human Participants and Students as Researchers (updated 09/2022) Guidelines for Oral Consent
The Research Ethics Board (REB) exists to ensure that all research involving human participants conducted within the jurisdiction of University Health Network (UHN) meets the required standards of ethical and research conduct. To learn more, please click on the buttons below. University Health Network (UHN) is a research hospital affiliated ...
Documentation must include a Research Ethics Board Attestation that "for each clinical trial site, an attestation, signed and dated by the Research Ethics Board for that clinical trial site, stating that it has reviewed and approved the protocol and informed consent form and that the board carries out its functions in a manner "consistent ...
As part of its commitment to keeping studies on TRACKTM and to reduce the record-keeping burden on Sponsors/CROs and Sites, Veritas IRB has incorporated the Health Canada 'Research Ethics Board Attestation' (REBA) text into its Approval Forms. This is permitted by Health Canada, which specifies that the IRB Approval Form 'does not need to ...
The CanadaFDR and the G-CanadaCTApps, require the sponsor to complete and retain the Research Ethics Board (REB) Attestation (CAN-8) and Qualified Investigator Undertaking (QIU) (CAN-37) forms at each trial site, while submitting in electronic format the Clinical Trial Site Information Form (CAN-6) to the appropriate HC Directorate for each ...
An attestation must be completed by the Research Ethics Board that reviewed and approved the clinical trial protocol and informed consent form for this clinical trial at the site below. The completed attestation must be retained by the clinical trial sponsor for a period of 15 years.
It is the Health Research Ethics Boards' policy not to sign individual Health Canada REB Attestation Form. This letter serves as a substitute for this form and is to be taken into consideration along with any specific study approval that will be issued, as fulfilling the requirements set forth by Health Canada in regards to REB Attestation.
6.1.1.Complete and sign a Research Ethics Board Attestation (REBA) form or receive an equivalent document from the Research Ethics Board, for each Clinical Trial Application . SOP007_03 Page 4 of 9 Effective Date: 01-Jun-2021 and Investigational Testing Authorization. Retain this document with the Essential ...
Consent process. Applicants must apply for ethics review before the start of the study. Note that the REB cannot retroactively review research involving humans. A letter of approval from the Decisional Authority of Health Canada or PHAC and a Certificate of Ethics Review must be obtained from the REB before the research begins.
The Oak Valley Health Research Ethics Board (REB) will not issue a signed REBA Form for Health Canada regulated research. The Guidance for Clinical Trial Sponsors states that the REBA Form, or similar documentation, meeting the requirements of Part C, Division 5 of the Food and Drug Regulations, is acceptable. The Oak Valley Health REB approval ...
Ethics Application Forms. These forms are provided for your protocol submission and revision. If you have any questions about the appropriate form to submit, please contact [email protected]. Ethics Application Templates. These templates are provided to assist you in creating the required documentation for use with your protocol submission and ...
There are two Research Ethics Boards (REB) at the University of Ottawa. The Social Sciences and Humanities REB evaluates all research projects originating from School of Management, and the Faculties of Arts, Education, Law and Social Sciences (except School of Psychology). The Health Sciences and Science REB evaluates all projects originating ...
HREBA Departmental or Site Approval Form - version April 2018. [email protected]. [email protected]. [email protected]. HREBA. 1500-10104 103 Ave NW. Edmonton, AB T5J 0H8. 1-877-423-5727. Research Ethics Boards in Alberta.
As an academic health science centre, Sinai Health fosters a culture where everyone is a learner. We believe that the combination of energy, fresh thinking and knowledge transfer is a reciprocal relationship that benefits the hospital, the student - and ultimately our patients.
It is the Health Research Ethics Boards' policy not to sign individual Health Canada REB Attestation Form. This letter serves as a substitute for this form and is to be taken into consideration along with any specific study approval that will be issued, as fulfilling the requirements set forth by Health Canada in regards to REB Attestation.
All research has ethical implications, whether it involves, humans, animals or anonymised datasets. Research Ethics Committees (or Ethical Review Boards) help researchers consider and prepare for ethical issues that their research might raise. The main way Research Ethics Committees do this is by reviewing a researcher's ethics application ...
An attestation must be completed by the Research Ethics Board that reviewed and approved the clinical trial protocol and informed consent form for this clinical trial at the site below. The completed attestation must be retained by the clinical trial sponsor for a period of 15 years.
The ethical approval of research at the University of Greenwich operates at two levels: The University Research Ethics Board (UREB) approves staff research projects which require ethical approval and some student projects.; Faculty Research Ethics Committees (FRECs) approve most student projects which require ethical approval and review other ethics applications before they are submitted for ...
(including the Florida Code of Ethics for Public Employees) and relating the codes to ethical issues in contemporary professional life. 5. Students will evaluate codes of ethics in the professional, corporate and government context by: a. identifying and critiquing specific code(s) of ethics relating to their chosen careers.
Complete and submit the online application. The application period opens January 16, 2024, and the deadline for submitting applications is March 31, 2024, with Florida Realtors Board Certified Professional status awarded at the August Florida Realtors Board of Directors meeting. Every two years, you must recertify your endorsement.