Principle:

Drug advertising should be consistent with the Health Canada approved Terms of Market Authorization (TMA). 

Rationale:

Advertising content which is inconsistent with the TMA would contravene section 9.1 of the Food and Drugs Act.

Application: 

The subgroup(s) must be part of the population segment covered by the product indication AND the specific patient group(s) must be consistent with the TMA. Claims relating to subgroups can only  appear after prominent presentation of the relevant Health Canada approved indication (i.e. disclosure of the overall indicated population). The observation must not contradict anything in the TMA (with respect to magnitude, direction, or duration).

Principle:

Claims should be based on assessments which were designed to measure the observed outcomes.

Rationale:

To minimize biases (e.g. selection and measurement bias).

Application:

The subgroup and the method/number of analysis must be pre-defined in the study protocol.  Data on file, such as the statistical analysis plan, may be used to demonstrate that this requirement has been met.   

Principle:

Baseline features should be comparable across the subgroups and the overall study population.  

Rationale:

This is important to avoid selection bias and an imbalance in the prognostic factors. 

Application:

The subgroup variable(s) must be measured prior to randomization of the overall population. 

Principle:

Exploratory analyses are not accepted.

Rationale:

Planned confirmatory analysis empowers a priori decisions on how to control the risk of type 1 error

Application:

Must meet all following criteria:

• Must have similar results to those seen in other studies
• Must have results that are consistent with a biologic rationale
• The statistical analysis must discuss how the risk for type 1 error was minimized

Principle:

For claims of benefit, the results of a subgroup analysis must demonstrate consistency of effect to the overall study population.

Rationale:

The study is powered to assess the primary endpoint. A subgroup analysis in a secondary endpoint cannot salvage a failed study.

Application:

Outcome must be directionally consistent with the overall study population.

Principle:

The claim must not mislead.

Rationale:

The message should not lead the reader to misinterpret the subgroup analysis to be the primary endpoint.

Application: 

The APS must clearly identify that the outcome is a subpopulation (i.e. within the claim, not a footnote) except where this assessment was the primary endpoint.