Transcript Developing Consumer Marketing Claims within the Clinical

Identifying, Validating and
Substantiating Claims for
Labeling and Advertising
Louis A. Morris, Ph.D.
Outcomes Research Conference
February 24, 2004
Objectives
• Why is it important to prospective develop
claims?
• What claims should we develop? (Identification)
• How do we know we are measuring the effect we
want to measure? (Validation)
• What information do we need so that FDA will not
object to our claims? (Substantiation)
Claims Development
Clinical Trials
PI +
Scale Development
Claim
Planning
HCP’s
Audience: MCO’s
Patients
Perceptual Analysis
What is the starting point for claims development?
Role of the PI
Roadmap for
Drug
Development
Claims Basis
PI
Additional
Substantiation
License to
Market
HCP’s MCO’s Pat’s
Label or Advertising Claims
• Label (approved claims) [Plan A]
– Indications must be in label
– Other information of clinical significance
• Meet content and format requirements
– Relevance for prescribing decision
• Advertisements (permitted claims) [Plan B]
– Meet advertising substantiation and disclosure
requirements
– Marketer decides, FDA reviews
Patient Outcomes Assessment
Sources and Examples
Clinician - Reported
For example,
Global impressions
Observation & tests
of function
Physiological
Caregiver - Reported
For example,
For example,
FEV1
HbA1c
Tumor size
Dependency
Functional status
Patient - Reported
For example,
Functional status
Symptoms
HRQL….Satisfaction
Evaluation Criteria
Perceptions, Linkages
Global Impression
Well-being
Treatment adherence
PRO Interpretation Typology
Self-Observation
Emotional States
Physical States
Behavioral States
Bodily
Response
Symptom Global
ADL
HRQL
Criterion
depression bother
bathing asthma- Satisfaction
anxiety
walking HRQL
pain
Productivity
Compliance
indication --------clinical studies findings
FDA Claims Perspective
• False – inconsistent with label
– Lacks substantial evidence
• Misleading - logical inferences
– local coherence - “Avoid Colds, take X”
– global implication - comparative claims
• FTC Differences
– What is the Claim? (audience interpretation)
– External evidence for implied claims
Claims Planning:
Working Backwards
• What do you want to say?
– Sufficient research/planning to understand positioning,
specific claims
– Specify the claim (envision headline)
• What substantiation do you need?
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Claims to be communicated
Scale development
Clinical trials
Risk information inclusion
Limits on Claims: We can lead a horse to water, but can’t
make him recite the pledge of allegiance
Three Phases of Claim
Development
• Identifying Desired Claims
– meaningful to patient or prescriber
– positioning statement
• Developing Meaningful &Validated Measures
– scale development
• Obtaining Substantiating Evidence
– substantial evidence, clinical trials
Phase I: Identifying the Claim
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Product Attributes
Results from Using (benefits)
How it makes Patient/Prescriber Feel
What it helps Patient Achieve
(Actual  Ideal State)
• Fulfills Needs, Achieves Expectations, Produces
Satisfaction, Sets New Norm
• Persuasion Parameters
• Instrumental to Achieving Valued Goal
Developing Meaningful Claims
• Need to understand:
– How do prescribers/patients conceive of products/features?
– Why would prescribers/patients want to use product?
• What are their product-related goals?
• How does the product fit in with their goals?
• What would motivate the patient to ask for or prescriber to use?
– What do we communicate to the patient or prescriber?
• Product features of value to the patient or prescriber?
• Benefits of using the product?
• Symbolic associations of significance?
Phase I: Research Approaches
• Needs Analysis – Gaining Insights
– Focus group (phenomological, clinical, exploratory)
– Projective Techniques
• Fill in the blank (the thing I like best about my cholesterollowering medicine is _____)
– Systematic Quantitative Measures
• Approaches
– HRQL (Disease) – is disease outcome important?
– Benefit (Treatment) – is treatment outcome important?
– Means End Chain – why is it important?
• How does product attribute link to patient or prescriber values?
• How does product use fit with consumer goals?
Study Product – Value Linkages
• Means-End Chain Analysis
– Examine Product Attributes (distinctions)
– Relate to Consequences
– Link to Values
• Process of Studying
– Laddering
• Generate ACV chains
• Question Posed Repeatedly: Why is that important?
• Compile into HVM
Hierarchical Value Map (HVM)
More Time with Family
Values
Go More Places
Person
Conseq.
In Control
No Fear
Better Treatment
Easy to Remember
Product
Easy Use
Easy to Breathe
Attributes Opens Airways Take Once-Day
Inhaler
Translating HVM to
Meaningful Endpoints
• What are the important concepts/claims?
– Leverage points offer clues
• no fear, do more things, in control
– Showing linkages is important
• How complex is the concept to be communicated?
– concrete attribute vs abstract goals vs valued behavior
• Face validity vs construct (validity) vs symbolic scenario
– Once-a-day, Easy-to-use, Spend time with family
• Further substantiation/research needed?
– Laddering offers insights, not definitive outputs
– Examine complexity, subjectivity, multidimensionality,
consumer interpretability, existing substantiation
Phase 2: Measurement
Determination
• Examine Proposed Claim
– Already in label/additional measures
– Single (concrete attribute) or multiple items (abstract
concept)?
• Scale Development
– Single or multidimensional
• Validity Study(ies)
– Surveys or trials
– Psychometric properties
Stages for developing
a PRO Claim
Hypothetical basis for
PRO as a criteria
of evaluation
Desk research
Literature review
Patient interviews
Study design
Preliminary protocol
Discussion of PRO concepts with clinical / marketing team
Desktop evaluation of available instruments
Selection of instrument(s
Approval by authors of instruments
Further validation work?
Translations & Psychometric validation
Development of a new
questionnaire
Validation
Translations & Psychometric validation
Integration in the trial protocol
Marquis, 2002
Scale Psychometrics
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Validity
Reliability
Sensitivity
Responsiveness
Minimally Important Difference
Scale Development
• Measures a complex concept
– Fair sampling of items
Amount
Cognitive--------Physical
How do we know we are
measuring what we want to
measure?
• Validity - process not a characteristic Understanding what is measured
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Face Validity - examine items
Content Validity - coverage
Construct Validity - any theory?
Concurrent Validity - positive correlation
Discriminative Validity - negative correlation
FACT-Fatigue Subscale
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I feel fatigued – face validity
I feel weak - physical outcome
I feel listless (washed out) – logical outcome
I feel tired
I have trouble starting things because I am tired – (cognitive)
I have trouble finishing things because I am tired
I have energy – the opposite, negate yea saying, halo effect
I need sleep during the day - outcome
I am too tired to eat
I need help doing my usual activities – (social)
[Plus others]
Correlate with Red Blood Cell Levels - Anemia
How do we know we are
measuring a concept
consistently?
• Reliability
– Within the same scale
• inter-item
• Chronbach’s alpha
– Over time
• test-retest
How do we know that our
measures can pick up differences
that actually exits?
• Sensitivity
– Type of scale items
• I am not tired at all
• I am so tired I must go to sleep right now
• I am having trouble concentrating
• I am feeling a little bit sleepy
2
items
How do we know that our
measure corresponds to changes
in the variable in question?
• Responsiveness
– Correlate changes in direct measure of clinical
outcome (Red Blood Cell Count) with changes
on scale (tiredness).
How do we know that an
observed effect is clinically
meaningful?
• Minimally Important Difference
– Smallest scale difference judged to be
meaningful (e.g., where a change in therapy
would be warranted)
– Effect Size
Developing a Scale?
Boredom Scale
• Conceptual - what is boredom?
– Other scales? – literature, experts
– Boredom effects, validation methods
• Operational - Item Generation/Reduction/Validation
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modular, adaptation from general scales
focus groups
initial question design (scale measure type)
ratings: How important are each of these items?
Factors Analysis - how many dimensions?
Validation studies - psychometrics
Clinical Impact (substantiation studies)
Selecting a Scale
• Apply all FDA considerations
– Validity in my population?
– May need a pilot to validate
• Practical Aspects - will people fill it out?
– Number, complexity of items
– “Involvement” with scale
• Bias – Leading questions, socially desirability, yea-saying, etc.
• Use in marketing
– May require “as measured by” language as well as
explanation of the scale
Phase 3: Substantiation
• Is the Claim truthful?
– FC&C Act Prohibits Misbranding
• Cannot be false or misleading “in any particular”
• Express and Implied Claims
– Description accurate?, context sufficient?
• Risk disclosures
• Confidence in Measurement
FDA Review Considerations
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Claim specification
Instrument development
Instrument validation
Study design
Data analysis plan
Interpretation of results
Reporting of results in approved labeling or
promotion
Uh-Oh
Homemade
Sales Aid
DDMAC Letters
• Duragesic (serious pain)
“Health related QoL claims such as these
require substantial evidence in the form of
adequate and well controlled studies
designed specifically to address these
issues”
DDMAC Letter
Neuronton (seizures)
Misleadingly claims improvement in QOL
parameters based on the NEON study. The NEON
study is not considered substantial evidence for
claims of QOL improvements because it is not a
controlled study.
Ad ran in
Europe
without
objection
DDMAC Letter
• Fosamax (prevention of osteoporosis) 6/20/01
– Fosamax web site: link to other web pages within site
titled “Preserving Your Independent Lifestyle.”
– Use of this phrase in the context of product-specific
promotional materials misleadingly implies an outcome
of Fosamax treatment that has not been demonstrated
by substantial evidence. The claim is misleading
because it overstates the potential benefit of Fosamax.
Zanaflex (Jan 2002)
Secondary data must be consistent with label. Even if new
data is found, the data must be based on convincing studies
and must be consistent with label
Provigil (January, 2002)
Must convey indication accurately, not expand the perceived
usefulness of the drug
APLB Letter
• AVONEX (MS)
10/24/02
AVONEX delivers the highest rate of
satisfaction – 95%…are misleading because the
misrepresent the results of the survey…
• does not identify the number of patients (75 per
group, three therapies identified)
• represents (only) the those who responded to the
question
• Lumps together 60% very satisfied and 30%
somewhat satisfied
FDA Letters
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Need specifically designed studies
Need substantial evidence
Implied claims, avoid overstatement of benefit
Claims must be consistent with label
Claims must not promote for unapproved use
Must accurately (fully) present study results
Ran without FDA objection: 2 clinical trials
Conclusions
• Pharmaceutical Marketing
– Used to be a Biological Model (every product has a niche)
– Now is a Warfare Model (competition)
• Develop Claims/Messages to Communicate Benefits
– Efficiency, rapid adoption
– Plan A – get in Label
• Need to Develop Substantiation (substantial
evidence)
– Even if not included in label
– Plan B - Claims Dossier