Evidence based advertising in 2018
Channel your inner evidence ninja Speaker: Karen Rizwan, Reviewer, PAAB
Acceptable Sources of Evidence: The Terms of Market Authorization (TMA) (e.g. product monograph, product licence, package labeling) always an acceptable source of evidence provided the advertising presentation reflects appropriate: context & emphasis
But what about other sources? Acceptable Sources for Evidence: When sources other than the product monograph are used, we must pause to assess both: Consistency with the product monograph Credibility of the evidence
Focus on Clinical Trials
Focus on Clinical Trials
Within the limitations of the TMA with respect to: Indication Dosing Regimen Efficacy/Safety Information Outcome type Magnitude Direction Duration
Focus on Clinical Trials
Focus on Clinical Trials
Protocol consistent with TMA: Also consider the comparator Indication Dosing Regimen Efficacy/Safety Information Outcome type Magnitude Direction Duration
Focus on Clinical Trials
Appropriate steps are taken to ensure that the observation is not simply due to: Chance Methodological bias Confounding This is concluded by assessing study protocol: Design Implementation Reporting What does credible mean?
Study protocol Control arm Randomization for therapeutic claims Blinding for subjective endpoints (e.g. pain questionnaires) A priori (e.g. endpoint, subgroup, stats) Statistical analysis Valid endpoint/instrument
Endpoint Valid & Credible The instrument should be widely accepted as a measurement of drug outcomes in that specific patient group and condition. As evidenced by discussion of the endpoint/instrument 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
How is this applied? Published, peer-reviewed, well controlled and designed studies with statistical significance shown (Code s3.1.1) Comparative claims require support as above in a head-to-head study (Code s5.7) Validated, pre-defined endpoints (Code s5.8) To be considered evidence, claims must reach statistical significance (Code s5.9) i.e. no stats, no claim
Focus on Clinical Trials
Accurately interpreting findings Use the past tense (Code s2.1, 2.3, 5.11) In order to reflect past study findings (not forecasts of future clinical experience) e.g. Demonstrated, shown, In a study AND avoid generalizations Better than one TNFα Inhibitor does not mean better than all TNFα Inhibitors (even if Key Opinion Leaders say that in medical practice all options are similar)
Accurately interpret findings Applying the guidance docs Interpreting statistics Does the CI or p-value relate to that particular claim? Was the CI or p-value interpreted correctly? e.g. Inability to attain statistical superiority is not proof of non-inferiority or similarity Statistical significance clinically meaningful Statistical significance for a composite does not mean in the individual components are statistically significant A failed study cannot be salvaged by a secondary endpoint
Focus on Clinical Trials
Context/Emphasis Keep non-clinical messages separate from clinical messages (Code s3.1.4) Data presented in the TMA with a cautionary tone should not be presented as a product benefit When TMA contains content which would otherwise not be accepted in drug advertising, restrict the presentation to the content, context, and emphasis in the TMA (e.g. Special Study data from part II of a product monograph)
Let s Evaluate: From Jensulin TMA: Jensulin is indicated for glycemic control in type 2 diabetes It has warnings for use in patients with a history of CVD CV events were a secondary safety endpoint in clinical trials Code s3.1 Should reflect the context and emphasis of the TMA Cardio-protective is not the outcome that was measured be specific Code s2.4 Data presented in the TMA with a cautionary tone should not be presented as a product benefit
Let s Evaluate: From Jensulin TMA: Jensulin is indicated for glycemic control in type 2 diabetes It has warnings for use in patients with a history of CVD CV events were a secondary safety endpoint in clinical trials Code s5.9 No statistical analysis for the comparison between Jensulin and placebo (CI or p-value)
Focus on Clinical Trials
When is additional information needed? QUANTIFICATION QUALIFICATION OVERLY SELECTIVE PRESENTATIONS RELATIVE CLAIMS REQUIRE ABSOLUTE DATA BALANCING SAFETY INFORMATION
Quantification = the presentation of magnitudes typically to answer one of the following questions (is the claim measurable?): How fast? How long? How short? How powerful? How low? How high? How much more? How much less? Is there a need to quantify or qualify the claim?
Qualification = insertion of text which restricts the claim in some way For example: Claims relating to a study should be accompanied by the relevant study parameters (s5.11) Claims which are not clinically significant should be disclaimed accordingly (s2.6.2 & 3.1.4) e.g. Clinical significance has not been established Is there a need to quantify or qualify the claim?
Not showing the whole story various endpoints (at 2 weeks vs. 8 weeks) context (overall score vs. selected sub scores, composite endpoint) Can t systematically ignore negative findings Code section 5.12 Overly Selective Presentations
Superior efficacy in improving symptoms and feelings (p<0.05) All other subscales were p=ns Is the claim overly selective?
Drug A was more effective than Drug B with a 50% greater mean BP reduction P<0.05 A vs. B p<0.001 A & B vs. placebo Absolute BP reduction Difference (129 vs. 133) 50% BP reduction may only correlate to a few mm Hg difference vs. comparator (Code s4.2.3) Relative vs. Absolute Risk Reduction
What about other types of claims?
Published review papers Can be used to support efficacy claims such as 95% of patients taking drug X achieved skin clearance. 1. Yes 2. No
Published review papers Can be used to support content relating to non-pharmacological advice/tips such as Counsel patients to avoid picking at pimples 1. Yes 2. No
Recognized consensus guidelines Authoritative consensus guidelines can be used to support comparative safety claims such as Use drug X instead of drug Y to reduce the risk of hypoglycemia 1. Yes 2. No
Recognized consensus guidelines U.S. guidelines can be used for place in therapy claims in the absence of Canadian guidelines? 1. Yes 2. No
What about price claims? Avoid claims with pharmacoeconomic implications (e.g. cost ) unless there is supporting data (Code s5.10.1ii) If comparative, include price for all products based on an independent source (e.g. provincial formulary, wholesaler, etc.) Disclaimer: mark-up or dispensing fees not included and not clinically significant
Clinical/Therapeutic claims: RCTs which are published & peer-reviewed (Code s3.1.1) Acceptable Sources Comparative clinical/therapeutic claims (e.g., efficacy/safety): Must be a head-to-head RCT (s5.7) Blinding required if subjective endpoint (not required if objective endpoint) Statistical analysis required (e.g. p-value or CI) (Code s5.9) Place in therapy (e.g., first-line): Canadian consensus guidelines (Code s3.2)
Market Share: Authoritative recognized independent source (Code s4.2.2 & 5.10.2) Acceptable Sources (Continued) Non-clinical Preference Claim (e.g., taste preference): Survey which is either published & peer reviewed OR Survey designed, conducted & analyzed without sponsor s influence (Code s5.10.2) Non-clinical Comparisons Across product monographs: Kinetics, MOA, Indications, Contraindications, Warnings, Interactions, Dosing, Dosage form availability - NOT efficacy or side/effects (Code s5.10.2iii) Price Comparisons: Independent data. Must be the same source for all comparators (Code s5.10.2) 38
Abstracts Symposia poster presentations Data on File references unless part of NDS with proof of acceptance Review articles Opinions / Editorials Letters-to-editor Previous advertising Supplements Testimonials Adverse drug reaction reporting systems Pooled data What not to use as a reference
Additional resources: https://www.paab.ca/resources.htm
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