Health Canada outlines when off-label use is not considered investigational in a clinical trial

Health Canada have issued a notice which outlines the circumstances in which the off-label use of an authorised drug in a clinical trial would not be considered investigational. The notice went into effect on 5th June 2019, and Health Canada have stated that the notice will “serve as interim interpretive guidance until amendments can be made to the Food and Drug Regulations.”

Health Canada explained that previous interpretation of the regulations governing clinical trials meant drugs used off-label in a clinical trial were required to be identified as investigational in a clinical trial application (CTA). However, there are circumstances in which an authorised drug used off-label in a clinical trial may not need to be identified as investigational if it is not the subject of the clinical trial. Therefore, clinical trial sponsors are required to state whether a drug used off-label in a trial is investigational or not based on whether the drug is the subject of the trial. If the sponsor and Health Canada agree that the use is not investigational, specific requirements for labelling and record keeping under Part C, Division of the Food and Drug Regulations will not apply.

Health Canada have explained that for an off-label use to not be considered investigational, sponsors are required to state the proposed off-label use and describe how the off-label use is streamlined with the current or recognised medical practice, including documenting how the off-label use is “not the subject of investigation in the clinical trial.”

It is important to note that a drug that is used in an off-label manner in the comparator arm of a trial or as part of standard therapy that another drug is being used to supplement in the investigational arm may not be considered investigational under Health Canada’s notice.

Additionally, sponsors are required to state the risks or uncertainty with the drug and off-label use with regards to the clinical trial. The notice also outlines that sponsors should explain whether the off-label use significantly increases the drug’s risks or reduces the acceptability of those risks compared to its authorised use(s).

To read Health Canada’s notice to stakeholders on the investigational use of marketed drugs in clinical trials, please click here.