Transcript Regulatory/Ethical Issues: Analysis and Review

Regulatory Issues in
Outcomes Labeling & Advertising
Louis A. Morris, Ph.D.
July 17, 2001
Objectives
• Why are outcome claims becoming more
important to drug development?
• What types of outcome claims are relevant
to pharmaceutical communications?
– Health Economics
– Quality of Life
– PROs
• How are these regulated by FDA?
Clinical and Marketing
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Testing
II
III
Approval
Product Adoption
Intro Growth Maturity Decline
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Inception
Approval
TIME
How to Jump Start Sales?
B
Targeting Audience Decisions
Gatekeeper
Influencer
Prescriber
Buyer
User/Monitor
HCPs MCOs PATs
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Product Profile to Label
Think Forward
Target
Product
Profile
•What label is desirable?
• How will we get there?
Development Plan
Phase I, II and III
Desired
Product
Label
•Development plan to deliver label
Plan Backwards
• Appropriate studies to support
Lawry 1999
claims
Claims Development
Clinical Trials
PI +
Scale Development
Claim
Planning
HCP’s
Audience: MCO’s
Patients
Perceptual Analysis
Not just through the FDA, but through to the market
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)
– Indications must be in label
– Other information of clinical significance
• Meet content and format requirements
– Relevance for prescribing decision
• Advertisements (permitted claims)
– Meet advertising substantiation and disclosure
requirements
– Marketer decides, FDA reviews
Types of Outcomes Claims
• Theoretically Any Endpoint
• For Purposes of This discussion
– Health Economic
– Health Related Quality of Life (HRQL)
– Patient Reported Outcomes (PROs)
• Includes HRQL and other claims
Health Care Economic
Information
• Section 114
– 218 words, all confusing
– effective Feb. 19, 1998
• Economic Information Not False or
Misleading If:
– only to formulary (and similar) committees
– approved indication only
– “competent and reliable scientific evidence”
What is Health Economic
Information?
• “… any analysis that identifies, measures,
or compares the economic consequences,
including the costs of the represented health
outcomes, of the use of a drug to the use of
another drug, to another health care
intervention, or to no intervention.”
• Substantiation to Upon FDA Request
Standards for Review
• “Methods for establishing the economic
costs and consequences used to construct
the health economic information would be
assessed using standards widely accepted
by economic experts.”
• “…clinical outcome assumptions … experts
familiar with evaluating the merits of
clinical assessments.”
The Law (Committee Report):
Economists’ Standard
Cost
Effectiveness
Clinicians’ Standard
FDA’s Previous Position (1995 Draft Guidance):
Disclosure
Cost
Effectiveness
Adequate and well
controlled studies
What is an Economic Claim?
Side Effect Treatment
QALYs
Hospital Room Charges Doctor Visits
Blood Pressure
Laboratory Tests
FEV1
Refills
Drug Costs
Hospital Room Days
Overall Impact
• Immediate
– The door is opened
• Deeper Look
– What is really here?
– Uncertainty in interpretation
• some FDA submissions but not many
• Self-implementing
– FDA had promised Guidance but none came
• Little industry interest
Quality of Life
• Humanistic Data
– represents patients’ perspective
– HCP & MCO audiences
• Rise in Disease-Specific Scales
– sensitive; more likely to show differences
– may need to develop/validate scale
• Inclusion in Label or Advertising
– support advertising claims
– in clinical trials section (18)
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
Source of Claim
ADL
QALYs
QALYs
Cost
PROs
HRQL
Bother Discomfort
Satisfaction
Productivity
Symptoms
Meyer, Burke, 1999
Three Phases of Functional
Claim Development
• Specifying Desired Claims
– meaningful to individual
– positioning statement
• Developing Meaningful &Validated Measures
– importance, scale development
• Obtaining Substantiating Evidence
– substantial evidence, clinical trials
Phase I: Specifying the Claim
• Needs Analysis
– Focus group (phenomological, clinical, exploratory)
– Projective Techniques
• Fill in the blank (the thing I like best about my cholesterollowering medicine is _____)
• Importance to Audience
– HRQL (Disease) – is disease outcome important?
– Benefit (treatment) – is treatment outcome important?
– Means-End Chain – why is it important?
Phase 2: Measurement
Determination
• Examine Proposed Claim
– Single or multiple items?
• Scale Development
– Single or multidimensional
• Validity Study(ies)
– Surveys or trials
– Psychometric properties
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, sufficient context
• Risk disclosures
• Confidence in Measurement
– “All claims of clinical benefit require
substantial evidence” Laurie Burke (5/00)
Express and Implied Claims
Deceptive
Not Deceptive
True
A
B
False
C
D
Absenteeism in productivity claims:
Relenza
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DDMAC Letters
• Neoral (transplant rejection) (3/7/00)
– Unsubstantiated Claims - “imply Neoral has an
effect on physical, mental and social
functioning that has not been demonstrated by
substantial evidence”
• Duragesic (serious pain) 3/20/00
– “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”
Truthful Claims Substantiation
• Substantial Evidence
– Uses/Indications; comparative claims
• Adequate and well controlled clinical investigations
• Efficacy standard (redefined by FDAMA)
– one AWC trial + cooborating evidence
• Consistency with approved package label
• Convincing Evidence (surveys, preferences)
• Being reexamined by FDA
PROs: FDA 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
Psychometric Qualities
• Evidence of validity, reliability, sensitivity,
and responsiveness
• Demonstrated validity in previous research
– cannot change order, pick items
• Clinical Meaningful Differences
• Supporting documentation to FDA