Code Standards

5 Making Comparisons

Forming part of the PAAB Code, reproduced here in bold, (Section 5.1 to 5.6) is the text of the Part 5 “Policy” from the Health Canada directive entitled Principles for Comparative Claims Related to the Therapeutic Aspects of Drugs.

Consistent with the provisions of Section 9 (1) of the Food and Drugs Act, pharmaceutical manufacturers are required to observe the following principles in making claims that compare the therapeutic aspects of drugs:

5.1

The compared drugs/products have an authorized indication for use in common, and the comparison is related to that use; or, in addition to the common indication for use, a second authorized indication is claimed as an added benefit of the advertised drug, and

5.2

The comparison is drawn between drugs under the same conditions of use (e.g. equivalent part(s) of their authorized dose ranges (maximum vs. maximum dosage), in a similar population, and 

5.3

The claim does not conflict with the Terms of Market Authorization of the compared products (Note 1), and

5.4

The claim is of clinical relevance in humans, i.e. relevant to treatment selection, and, where this is not readily apparent, its clinical relevance can be justified by the sponsor, and

5.5

The evidence generated to substantiate the claim is conclusive and based on:

i) Consideration of all relevant data, and

ii) Scientifically accurate, unbiased, reproducible data obtained from studies conducted and analyzed to current scientific standards using established research methodologies and validated end points, and

iii) Appropriate interpretation of the data (Note 2).

5.6

The claim and its presentation should:

i) Identify the compared entities (Note 3), and

ii) The medicinal use related to the claim where this is not readily apparent (Note 4), and

iii) Not obscure the therapeutic use of the advertised product/ingredient (Note 5), and

iv) Not attack the compared drug product(s)/ingredient(s) in an unreasonable manner, and

v) Be expressed in terms, language and graphics that can be understood by the intended audience.

Advertisers are responsible for ensuring that comparative claims that fall within the scope of these Health Canada Principles, meet these requirements. Furthermore, all comparisons must satisfy the requirements of the full PAAB Code, including the following provisions:

5.7

Comparative claims of efficacy and safety generally require support of evidence from head-to-head, well-designed, adequately controlled, blinded, randomized clinical studies. Open-label studies are generally not considered to be a high level of evidence and are not acceptable if subjective end-points are included in the study. Comparative claims should be consistent with current medical opinion and practice. Canadian guidelines are to be adhered to. In the event that they are not available, see the following document on what constitutes current medical opinion.


Current Medical Opinion 

5.7.1

Adverse events and clinical efficacy data quoted from two or more TMAs or derived from studies that were not head-to-head, are not acceptable support for comparative claims of clinical safety or efficacy. This is due to the fact that factors such as study methodologies, patient populations, dosing and measurement criteria used in the separate trials can vary widely. Furthermore, a side-by-side presentation of these adverse events and efficacy data, which lack comparability, could leave a misleading impression and does not meet the PAAB Code acceptance standards.

5.8

Methodologies, endpoints and independent review. To be considered as evidence, clinical studies must use established research methodologies and validated endpoints. To aid in the assessment of these study parameters, PAAB looks for evidence that the full study results have been subject to independent review, such as that found by achieving the publishing of study results, including statistical analyses, in a peer-reviewed journal. (Note 6)

5.8.1

Alternatively, unpublished data are regarded as having received independent review when:

i) There is evidence that the full study manuscript has been accepted by the editor of a peer-reviewed journal for future publication, or alternatively when

ii) The data have been reviewed as part of a submission to Health Canada and there is evidence of acceptance (such as inclusion in the TMA).

5.8.2

When presented only in the following form, study design and results analyses are not regarded as having been subject to independent review and are not sufficient evidence to be used as reference support for advertising claims:

i) Abstracts presented at conferences and in journal supplements.

ii) Papers published in journal supplements unless the advertiser can demonstrate that the supplement has also been subject to an adequate peer review process.

5.9

Analysis of Data: To be considered as evidence, results must achieve an acceptable level of statistical significance. Where confidence intervals (CI) and p-values are both available, the manufacturer may decide to report both. The use of 95% CI is encouraged in preference to p-value. The use of 90% CI is acceptable for presentations of pharmacokinetic data. Failure of study results to demonstrate a statistically significant difference in the measured effect is not sufficient to support a claim of equivalence between the treatments studied.

5.10

All direct and indirect comparisons must not mislead and be supported by reliable current data.

5.10.1

The following types of claims are subject to the requirements noted:

5.10.1.i

i) Comparisons of adverse events or efficacy of a product or drug ingredient may be supported by a peer-reviewed, published meta-analysis of data from studies in which the conditions of use of the compared drugs are consistent with those authorized in Canada.

5.10.1.ii

ii) Pharmacoeconomic and quality of life claims must be supported by high-quality studies. Disclosure of study parameters (See ) is important for interpretation of results.

5.10.1.iii

iii) For comparisons of non-clinical data (e.g. pharmacokinetics and pharmacodynamics), no direct or indirect clinical conclusions may be made in advertising unless a strong correlation can be established (e.g. where the rate of absorption is a direct measure of the onset of symptom relief).

5.10.1.iv

iv) Price comparisons that imply or suggest therapeutic equivalence are not acceptable. A disclaimer may be appropriate.

5.10.2

The following classes of claims are subject to these requirements noted:

i) Market share and price claims, must be based on and referenced to, current authoritative data and must not state or imply therapeutic equivalence.

ii) Other non-therapeutic product claims, such as taste or packaging, require support from adequate, unbiased and statistically valid Data.

iii) Information from two or more TMA on products’ properties (Note 7) and on instructions for use or use limitations (Note 8may be acceptable as side-by-side presentations and in text form. While the Code permits products to be accurately differentiated by these parameters, no clinical significance must be stated or implied where none has been proven, as is required under the Code for any statement. To ensure that clinical significance is not implied, a disclaimer may be required:

“Data from separate product monographs; comparative clinical significance has not been proven.”

Any such side-by-side presentation or statement must be complete, in that other data relevant to the presentation also contained in the TMAs must not be omitted. The presentation or statement must not be accompanied by a heading that implies an overall comparison of clinical efficacy or safety.

5.10.3

In submitting the claim for review, the advertiser attests that the data is current and does not conflict with the body of evidence in the field.

5.11

Disclosure of study parameters. The claim should be accompanied by or linked to disclosure of relevant study parameters that would aid the reader in interpreting the data such as patient numbers and p-value and/ or confidence intervals (CI). This information should be in prominent type size (a minimum of 8 point on 9 point). In no circumstances would extrapolation of the claim beyond the actual conditions of the supporting studies be acceptable. Information such as study methodology, description of patient type and number, disease severity, dosage range, study sites, etc. may appear with the product information.

5.12

Context. Selective data presentations or claims which distort study findings, or which are out of context with study conclusions, are not acceptable.

5.12.1

All advertising is subject to Code requirements for risk/benefit balance.

5.13

Equivalence. Bioequivalence claims are based on valid comparative data, normally to standards currently in use by Health Canada. Accurate statements may be made about the interchangeability of products recognized on various formularies. Claims of therapeutic equivalence must be based on comparative evidence.

5.14

Formulation. Studies using non-Canadian products are not accepted unless the advertised Canadian product is identical (for example identical master formula) to the corresponding non-Canadian product used in the original studies. A letter from the sponsor’s Medical/Regulatory Department would be required.

5.15

Scare tactics. Advertising that induces fear or uses scare tactics to introduce unwarranted concern will not be accepted.

5.16

Superlatives. Unless substantiation can be provided, advertisers may not claim or imply that a product has a superlative feature or function (e.g., comments such as most effective, or least toxic), or is accorded special status (such as being unique). Similarly, advertisers may not, without substantiation, claim or imply superiority or special status for a company, its personnel, services, or product line.

5.17

Trademarks. Copy must acknowledge competitors’ trademarks.

Notes
  1. For drugs subject to Division 8, Part C of the Regulations, the Drugs Directorate Policy: Changes to Marketed Drugs provides guidance on product information changes that require the filing of a Supplemental New Drug Submission, Notifiable Change etc. For drug products assigned a DIN but are not subject to Division 8, Part C of the Regulations, Section C.01.014.4 of the Regulations identifies the product information changes that require a new DIN application, provided the new information does not render the product subject to Division 8, Part C of the Regulations.
  2. Extrapolation beyond the actual conditions of the supporting studies is not acceptable.
  3. e.g. hanging comparisons such as “better”, “ faster acting” are unacceptable, as are vague statements such as “compared to the leading brand....”
  4. Where the advertised entity has more than one indication for use, it should be clear to which use the claim refers.
  5. e.g. the comparative claim should be afforded no more prominence than the therapeutic use.
  6. As defined by the International Committee of Medical Journal editors, a peer-reviewed journal is one that has submitted most of its published articles for review by experts who are not part of the editorial staff.
  7. e.g. drug pharmacokinetics, pharmacodynamics and pharmaceutical information.
  8. Indications, Contraindications, Warnings, Precautions, and information on dosage, administration and overdose.