Management of clinical trials during the COVID-19 pandemic: Notice to clinical trial sponsors

Health Canada is aware of the impact of the pandemic on the conduct of clinical trials, including the need for:

• participants to self-isolate
• deployment of healthcare personnel involved in clinical trials to other duties during this public health emergency, resulting in delays in completing certain tasks

As per paragraph C.05.010(b) of the Food and Drug Regulations (FDR), the sponsor must ensure that the clinical trial is conducted in accordance with the requirements of the protocol, which has been authorized by Health Canada and approved by REB(s). Health Canada recognizes that there may be an increase in protocol deviations during the COVID-19 pandemic.

The clinical trial site(s) should have a system in place to identify, document, assess and report all protocol deviations to the sponsor and REB in accordance with sponsor and REB requirements. These deviations need to be documented, to facilitate future analysis of the study findings. The sponsor should define and identify the protocol deviations to be reported. Unless the deviations may place participants at risk, sponsors will not be required to report these deviations to Health Canada.

Monitoring activities may need to be re-assessed, and should prioritize critical activities to ensure participant safety. It is advisable to document any changes and their impact. Processes may need to be changed: for example, an electronic alternative may have to be considered in place of a wet ink signature.

Eligibility assessment is to be carried out as usual. Persons should not enroll in a trial if they do not meet the pre-set inclusion/exclusion criteria. If by missing a pre-defined study visit, the safety of a participant may be put at risk despite implementation of appropriate mitigation measures, the sponsor needs to consider having the participant discontinue taking part in the study.

Halting recruitment or temporarily halting the trial may be required in some circumstances. If this happens, sponsors are to inform Health Canada using a clinical trial application notification (CTA-N).

The FDR do not prohibit the shipment of clinical trial investigational products (IP) from Canadian sites directly to patients. This approach would be acceptable for all product formulations (for example, tablets, injectables); however, the following considerations and/or requirements should be kept in mind:

• this approach can only be considered for drugs that a subject could take on their own (for example, subject already in a trial and on medication, and if the trial uses a medication that doesn’t have to be administered in a hospital/clinic setting or have any special conditions for handling)
• record keeping must comply with regulatory requirements of section C.05.012 of the FDR
  • as per C.05.012(3)(e), the sponsor must maintain complete and accurate records in respect of the use of a drug in a clinical trial, including records respecting the shipment, receipt, disposition, return and destruction of the drug
• the trial must always be conducted in accordance with Good Clinical Practices (GCP) and must comply with regulatory requirements of section C.05.010 of the FDR
  • it is the sponsor’s responsibility to ensure that the drug is administered in accordance with these Regulations
    
• products must be transported, handled and stored in a manner that mitigates the risk of exposure to temperatures outside labelled storage conditions (please refer to the Health Canada Guidelines for Temperature Control of Drug Products during Storage and Transportation (GUI-0069))

For detailed guidance on how to comply with Part C, Division 5 of the FDR, please refer to the Guidance Document: Part C, Division 5 of the Food and Drug Regulations “Drugs for Clinical Trials Involving Human Subjects” (GUI-0100).

Management of Clinical Trial Applications (CTA) during the COVID-19 pandemic

Clinical trial applications	Health Canada will prioritize the review of clinical trial applications designed to investigate the diagnosis, treatment and/or prevention of COVID-19. Sponsors may continue to file other CTA and CTA amendments according to Health Canada guidance. During the course of a CTA review, if sponsors are unable to respond to an Information Request (IR) within specified time lines, consider withdrawing the submission without prejudice and refiling when the information is available.
Participants affected with COVID19	Sponsors must decide quickly whether the study should be placed on hold (for instance, not administering the investigational product until the participant has recovered) or whether the participant’s involvement in the study should be discontinued. All participants affected by a COVID19 related study disruption should be documented by unique participant identifier, site and a description of how the individual’s participation was altered.
Trial participants	The ongoing safety of trial participants must be maintained. Risks and risk mitigation strategies related to use of any immunosuppressive agents should be discussed with medical professionals with expertise in immunology. Study participants must be informed of any risks/changes to the study and monitoring plan that could impact on their wellbeing. Documentation of medical oversight is required to determine participants’ eligibility to take part in study. Sponsors should discuss with local research ethics boards (REBs) whether it is in the best interest of the safety, welfare and rights of the participant to continue the participant as per the study protocol or to halt the study. Sponsors should discuss with REBs alternative methods of informed consent for the study or amendments to the study protocol if in-person visits are not possible (for example, electronic consent, recorded telephone consent).
Clinical trial visits	Investigators may need to evaluate whether alternative methods for safety assessment are feasible should participants not be able to come to the investigational sites as specified in the study protocol. Alternative methods may include phone contact, virtual visits via telemedicine or alternative care sites. Alternative locations for imaging studies and laboratory tests may need to be considered. If alternative monitoring is done, careful documentation will be required to capture the reason why it was done; the method used to collect the information; what data was collected; who provided the information; how the source of the information was verified and the reason why. Study protocol amendments will not be needed. The use of alternative sites may create issues of confidentially related to participant’s medical records (Electronic Health Record). Trial participants will need to consent to any identifiers leaving the original site and be assured that their confidentially will be protected.
Getting investigational product to participant	The Food and Drug Regulations (FDR) do not prohibit the shipment of clinical trial investigational products (IP) from Canadian sites directly to patients This approach would be acceptable for all product formulations (for example, tablets, injectables). This approach can only be considered for specific trial designs and drugs that a subject could take on their own (for example, subject already in a trial and on medication, and if the trial uses a medication that doesn’t have to be administered in a hospital/clinic setting or have any special conditions for handling). The investigational products must be transported, handled and stored in a manner that mitigates the risk of exposure to temperatures outside labelled storage conditions. Verification that the investigational drug has been received by the participant is required. Accurate documentation of the process in the participant’s study record is required.
Participant recruitments	Sponsors should consider suspending additional site activation and recruitment.
Site monitoring not possible	Any delayed site visits must be documented. Central monitoring of clinical trials should be considered.
Increased number of protocol deviations	Sponsors should consider alternate methods to prevent protocol deviations and document the reasons for any protocol deviations. Sponsors may consider submitting at regular intervals a cumulative list of deviations occurring in a particular study, rather than individual notifications.
Placing study on hold	Halting recruitment or temporarily halting the trial may be required. Documentation of reasons for halting recruitment or temporarily halting trial in study records is required Study holds should be notified to Health Canada as clinical trial notifications (CTA-N).
Reduction of burden for clinical trial notifications	Until further notice, sponsors do not need to file clinical trial site forms for non-COVID trials. Additionally, until further notice, sponsors do not need to submit notifications for non-safety-related changes for non-COVID trials.

Contact us

If you have any questions regarding this notification or regulation of clinical trials, please do not hesitate to contact Health Canada at one of the following addresses.

For pharmaceutical drugs

Therapeutic Products Directorate
Office of Clinical Trials
5th Floor, Holland Cross, Tower B
A/L 3105A
1600 Scott Street
Ottawa, Ontario
Canada K1A 0K9

Email: hc.oct.enquiries-requetes.bec.sc@canada.ca

For biologics and radiopharmaceuticals

Office of Regulatory Affairs
Biologic and Radiopharmaceutical Drugs Directorate
100 Eglantine Driveway,
Address Locator: 0601C
Ottawa, Ontario
Canada K1A 0K9

Email: hc.brdd.ora.sc@canada.ca

For clinical trial compliance

Regulatory Operations and Enforcement Branch (ROEB)
Clinical Trial Compliance Program
200 Eglantine Driveway,
Address Locator: 1903C
Ottawa, Ontario
Canada K1A 0K9

Email: GCP_BPC@hc-sc.gc.ca