Labeling claims for patientreported outcomes A regulatory perspective

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Labeling claims for patient-reported outcomes(A
regulatory perspective)

• FDA/Industry Workshop
• Washington, DC
• September 16, 2005
• Lisa A. Kammerman, Ph.D.
• Division of Biometrics 2

Center for Drug Evaluation and Research
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Disclaimer

• Views expressed in this presentation are those of
  the speaker and not, necessarily, of the Food and
  Drug Administration.

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Introduction

• Start early in development program
• Instrument selection
• Role of outcome in clinical study
• Issues to address
• Development and validation
• Clinically meaningful difference
• Implementation

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Introduction

• Trial Design
• Conduct of clinical study
• FDA review
• Instrument
• Study results
• And then . Labeling Claims

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To support a PRO claim

• Reliable and valid instrument
• Instrument measures concepts claimed
• Instrument measures impact of an intervention
• Well-controlled investigations

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Early in product development

• Identify endpoints
• Identify desired claims
• Discuss with FDA

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Selection of PRO Instrument

• Measures the claimed treatment benefit from the
  patients perspective
• Measures both the positive and negative benefits
  of the intervention

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Selection of PRO Instrument

• Specific to the intended population
• Specific to the characteristics of the conditions
  or disease treated

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Selection of PRO Instrument

• Three possible choices
• Existing instrument
• Modification of existing instrument
• New instrument

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Document, document, document!

• Development of instrument
• Patient involvement
• Population
• Goals
• Validation of instrument
• Format, wording
• Cultural issues, multinational studies
• Drug intervention studies

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Document, document, document!

• Concepts what will be measuredExamples
• Pain severity
• Psychological function
• Physical function

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Document, document, document!

• Domain Q concept Examples
• PFSF Desire, Responsiveness, Disinterest
• Physical function symptom improvement, physical
  abilities, ADL

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Document, document, document!

• Clinically meaningful difference
• Prospective plan
• Patient involvement
• Planned use in clinical study
• Primary evidence for efficacy
• Value-added
• Intended population

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Document, document, document!

• Implementation
• Training and instructions
• Format

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Trial Design Issues

• Prospectively defined
• Blinding
• Use of instrument
• Standardized instructions
• Standardized training
• Training and blinding of interviewers
• Recall to baseline

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Trial Design Issues

• Data capture
• Paper
• Electronic

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Role of PRO as an endpoint

• Primary evidence of efficacy
• Value-added
• Pre-specify
• Report findings, regardless of statistical
  significance and direction

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Analysis Plan

• Missing data
• Entire instruments
• Domains
• Items
• Visits
• Multiple endpoints

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And finally Labeling!

• Well-controlled studies
• Instrument reliably and validly measures the
  concepts claimed
• Convey both positive and negative effects
• Specific to the concept measured

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Summary

• Start early in clinical development program
• Talk to FDA review divisions
• Document, document, document
• Development of instrument
• Validation of instrument
• Clinically meaningful difference
• Implementation

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Summary

• Study Design
• Blinding
• Use of instrument
• Prospectively defined
• Analysis plan

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Summary

• Labeling
• Conveys both negative and positive effects
• Specificity to concepts measured