Principles:

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 observation must not contradict anything in the TMA (with respect to magnitude, direction, or duration). Claims relating to secondary endpoints must appear downstream from prominent presentation of the relevant Health Canada approved indication (i.e. disclosure of the indicated outcome).

Principle:

Where the endpoint is not in the TMA, the instrument must be reliable, valid and available to competitors to use in their trials. For surrogate outcomes, there must be evidence demonstrating that changes in a surrogate outcome are predictive of similar changes in final outcomes.

Rationale:

The outcome is only as valid/reliable as the instrument used to derive it.

The degree to which an outcome is affected by a drug versus other factors is important for decision making.

Application:

A secondary outcome should be widely accepted as a measurement of drug outcomes in that specific patient group and condition. This may be supported by showing that the endpoint is discussed in at least one of the following:

• a TMA within the therapeutic area (not required to be the sponsor’s TMA)
• consensus guidelines
• an authoritative medical text
• multiple peer-reviewed trials including at least one competitor’s trial.

For example, instruments designed by the manufacturer will not be considered unless this principle can be adhered to.

Principle:

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

Rationale:

To minimize measurement biases.

Application:

The endpoint must be pre-defined in the study protocol. 

Principle:

A secondary endpoint cannot salvage a failed study. 

Rationale:

The study is powered to assess the primary endpoint.

Application: 

Within the study itself, the secondary endpoint must be directionally consistent with the primary endpoint in order to be used as support for claims of benefit.  Note however that the PAAB may require disclosure of failed secondary endpoints to balance claims based on primary endpoints in order to avoid overly selective presentations (see 3.5 below).

Principle:

Presentations should not be overly selective.

Rationale:

Emphasizing only positive findings does not promote an element of trust.

Application:

The sponsor cannot selectively present positive secondary endpoints and ignore negative secondary endpoints.

There is no need to disclaim failed secondary endpoints when only the primary endpoint is promoted (except for particularly related secondary endpoints).

Examples of scenarios where a secondary endpoint would be considered to be particularly related to the primary endpoint include:

• Primary endpoint = diastolic blood pressure,  Secondary endpoint = systolic blood pressure
• Primary endpoint = composite of incidence of either death or stroke, Secondary endpoints = incidence of death along with and a separate endpoint for incidence of stroke

Principle:

The claim must not mislead.

Rationale:

The reader may mistakenly interpret that this is a primary endpoint.

Application: 

The APS must clearly identify that this is a secondary endpoint (i.e. within the claim, not a footnote).