Health Canada Notice Details When Off-Label Use is not Considered Investigational in a Clinical Trial
Health Canada last week issued a notice clarifying the circumstances in which the off-label use of an authorized drug in a clinical trial would not be considered investigational.The agency says the notice, which went into effect on 5 June, will “serve as interim interpretive guidance until amendments can be made to the Food and Drug Regulations.”
Health Canada says its previous interpretation of the regulations governing clinical trials led it to require drugs used off-label in a clinical trial to be identified as investigational in a clinical trial application (CTA).
However, Health Canada says there are circumstances in which an authorized drug used off-label in a clinical trial may not need to be described as investigational if it is not the subject of the clinical trial.
“As the off-label uses of an authorized drug can often be supported by well-established clinical practice overseen by provincial bodies that govern medical practice, this interpretation may be creating an unnecessary barrier to clinical research,” Health Canada writes.
Under the notice, Health Canada says clinical trial sponsors must 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 Health Canada agrees with the sponsor that the use is not investigational, certain requirements for labeling and record keeping under Part C, Division 5 of the Food and Drug Regulations will not apply to the drug.
For an off-label use to not be considered investigational, Health Canada says sponsors must detail the proposed off-label use and explain how the off-label use is “consistent with current or recognized medical practice,” as well as explain how the off-label use is “not the subject of investigation in the clinical trial.”
For example, a drug used off-label 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 the notice.
Sponsors are also required to detail the risks or uncertainty posed by the drug and its off-label use in the context of the clinical trial. Additionally, sponsors must explain whether the off-label use significantly increases the drug’s risks or decreases the acceptability of those risks compared to its authorized use(s).
Additionally, sponsors are asked to explain how the off-label use in question “aligns with Canadian ‘best medical practices’ and poses a ‘low risk’ to the population under study.”
Notice