Transcript Fair Balance (FB) - PAAB Training 2016

Evidence Based Advertising
“Don’t accept your dog’s admiration as
conclusive evidence that you are wonderful”
-Ann Landers
Guiding principles
Code section 2.1
– Advertising must be accurate, complete and clear
Code section 3.1
– Claims in advertising must be consistent with and
within the limitations of the Terms of Market
Authorization (TMA) (i.e. Product Monograph) or
prescribing information for products with no TMA
The TMA (e.g. product monograph) is always an
acceptable source of evidence.
BUT
Provided the advertising presentation reflects
appropriate context & emphasis
What about other sources?
When sources other than the TMA are used, we
must pause to assess both:
– Consistency with the product monograph
– The “credibility” of the evidence
A Focus on Clinical Trials
A Focus on Clinical Trials
PAAB s3.1
Message within the
limitations of the TMA (s3.1)
Indication
TMA Dosing Regimen
TMA Efficacy/Safety Information
• Outcome type
• Magnitude
• Direction
• Duration
A Focus on Clinical Trials
A Focus on Clinical Trials
PAAB s3.1,
5.1, 5.3, 5.14
Trial Protocol consistent with TMA
Indication
TMA Dosing Regimen
TMA Efficacy/Safety Information
• Duration
Takeaway….
Don’t forget to consider the
comparator!
• Code section 5 relates to comparisons
– Section 5.1: Authorized indication in common
– Section 5.2: Comparable dosing range
– Section 5.3: Consistent with comparator’s TMA
– Section 5.14 : Non-Canadian products
A Focus on Clinical Trials
PAAB s2.1,
3.1.1, 5.5,
5.7, 5.8, 5.9,
5.10,
What does “credible” mean?
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
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”
A Focus on Clinical Trials
PAAB
s2.3,4.1,4.2,
4.3
How to accurately
interpret 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 ACE Inhibitor does not mean
better than all ACE Inhibitors (even if Key Opinion
Leaders say that in medical practice all current
opinions are similar)
How to accurately
interpret findings?
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
How to accurately
interpret findings?
A study is designed and powered to assess the
primary endpoint
A failed study cannot be salvaged by a
secondary endpoint
Secondary endpoints
Example:
• Primary outcome:
• Bacterial eradication rates
– Non-inferiority (NI) attained
– Superiority NOT attained
• Secondary endpoints:
• Symptoms:
–
–
–
–
•
•
Sputum – NI
Fever – NI
Cough – NI and superiority
Headache – NI
Secondary endpoints must be directionally consistent with the
primary endpoint (see Guidance Document on Secondary Endpoints)
Secondary endpoints should be identified as such within the claim
copy NOT a footnote (Code section 3.1.10)
A Focus on Clinical Trials
PAAB s2.3,
2.6, 5.6, 5.12
Context/Emphasis
• Keep non-clinical messages separate from clinical
messages (Code s2.6.2 & 3.1.4)
(e.g. Non-clinical experience and clinical efficacy/safety claims)
• Data presented in the TMA with a cautionary tone
should not be presented as a product benefit
(e.g. “Low” incidence of event which is a boxed warning)
• 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)
A Focus on Clinical Trials
PAAB s2.4 &
3.5, 4.4, 5.6,
5.11
When is additional
information needed?
• Quantification (both implicit & explicit)
• Qualification
• Overly selective presentations (can’t
systematically ignore negative findings)
• Present absolute data when claims are
expressed in a relative way
• Balancing safety information
Is there a need to quantify or
qualify the claim?
Quantification = the presentation of magnitudes typically to
answer one of the following questions (is the claim measureable?):
How fast?
How long?
How short?
How powerful?
How low?
How high?
How much more?
How much less?
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Is there a need to quantify or
qualify the claim?
Qualification = insertion of text which
limits/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”
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Overly Selective Presentations
• Code section 5.12
• Not showing the whole story
– various endpoints (at 2 weeks vs. 8 weeks)
– context (overall score vs. selected sub scores,
composite endpoint)
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Exaggerated effect by omission
of ARR (Code s4.2.3)
• Relative vs. Absolute Risk Reduction
– 50% BP reduction may only correlate to a few mm Hg
difference vs. comparator
142
140
138
136
134
132
130
128
126
124
122
Drug A
Drug B
Placebo
P<0.05 A vs. B
p<0.001 A & B vs.
placebo
Absolute BP
reduction
Difference
(129 vs. 133)
Day 0
Day 30
“Drug A shown
more effective
than Drug B with a
50% greater mean
BP reduction”.
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FAQs
What does PAAB consider acceptable
references?
Answer
Clinical/Therapeutic claims:
Randomized controlled trials (RCTs) which are published &
peer-reviewed (s3.1.1)
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) (s5.9)
Place in therapy (e.g. first-line):
Recognized Canadian consensus guidelines (s3.2)
Answer (Continued)
Market Share:
Authoritative recognized independent source (s4.2.2 & 5.10.2i)
Non-clinical Product Claim (e.g. taste, packaging):
Survey which is either published & peer reviewed
OR
Survey designed, conducted & analyzed without sponsor’s influence
(s5.10.2ii)
Non-clinical Comparisons of Product Properties Across TMAs:
Complete comparison of Indications, Contraindications, Warnings,
Interactions, Dosing, Pharmacokinetics, Mode of Action, NOT efficacy or
adverse events (s5.10.2iii)
Price Comparisons:
Independent data. Must be the same source for all comparators (s5.10.2i)
What not to use as a reference
• Abstracts
• Symposia poster presentations
• Data on File references unless part of New Drug
Submission (NDS) with proof of acceptance
• Review articles
• Opinions / Editorials
• Letters-to-editor
• Previous advertising
• Supplements
• Testimonials
• Adverse drug reaction reporting systems
• Pooled data
See Code sections 3.1.1, 3.1.2 and 3.1.3
FAQs
What type of reference do I use to support noncomparative statements about competitor’s
products?
E.g. Traditional NSAIDs have a high risk of GI
ulcers
Answer
“You don’t”
Discussions of competing products should be
limited to acceptable comparisons involving the
sponsor’s product.
Examples of acceptable comparisons:
• Efficacy/safety comparison from head-to-head
clinical trial (s5.7)
• Product properties across TMAs (s5.10.2iii)
Disparaging Claims
•
•
•
•
Cannot unfairly attack competitors (Code s5.6)
Selective presentation of side effects
Only showing other product’s data
Only showing negative features of a
competitor.
•
“High risk of GI bleeds have been associated with the use of traditional NSAIDs”
•
“Did you know that Drug X is derived from pig’s urine? Drug A is derived from a natural
source”
•
“ Had enough of needle injections? Consider Drug A, now in a convenient once a week
patch”
PAAB Code update
July 1, 2013
• When surveyed, industry requested more
guidelines
• Guidance documents can be found at
http://www.paab.ca/advisories-guidance.htm
For more information
http://www.paab.ca/advisories-guidance.htm
Questions??