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

Labeling claims for patient-Labeling claims for patient-reported outcomesreported outcomes

(A regulatory perspective)(A regulatory perspective)

Labeling claims for patient-Labeling claims for patient-reported outcomesreported outcomes

(A regulatory perspective)(A regulatory perspective)

FDA/Industry Workshop

Washington, DCSeptember 16, 2005

Lisa A. Kammerman, Ph.D.Division of Biometrics 2

FDA/Industry Workshop

Washington, DCSeptember 16, 2005

Lisa A. Kammerman, Ph.D.Division of Biometrics 2

Center for Drug Evaluation and ResearchCenter for Drug Evaluation and Research

2FDA/Industry WorkshopFDA/Industry WorkshopSeptember 16, 2005September 16, 2005

DisclaimerDisclaimerDisclaimerDisclaimer

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

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


IntroductionIntroduction

• Start early in development program– Instrument selection –Role of outcome in clinical study

• Issues to address–Development and validation–Clinically meaningful difference– Implementation

• Start early in development program– Instrument selection –Role of outcome in clinical study

• Issues to address–Development and validation–Clinically meaningful difference– Implementation


IntroductionIntroduction

• Trial Design• Conduct of clinical study• FDA review– Instrument–Study results

• And then …. Labeling Claims

• Trial Design• Conduct of clinical study• FDA review– Instrument–Study results

• And then …. Labeling Claims


To support a PRO claimTo support a PRO claimTo support a PRO claimTo support a PRO claim

• Reliable and valid instrument• Instrument measures concepts

claimed• Instrument measures impact of an

intervention• Well-controlled investigations

• Reliable and valid instrument• Instrument measures concepts

claimed• Instrument measures impact of an

intervention• Well-controlled investigations


Early in product developmentEarly in product developmentEarly in product developmentEarly in product development

• Identify endpoints

• Identify desired claims

• Discuss with FDA

• Identify endpoints

• Identify desired claims

• Discuss with FDA


Selection of PRO InstrumentSelection of PRO InstrumentSelection of PRO InstrumentSelection of PRO Instrument

• Measures the claimed treatment benefit from the patient’s perspective

• Measures both the positive and negative benefits of the intervention

• Measures the claimed treatment benefit from the patient’s perspective

• Measures both the positive and negative benefits of the intervention



• Specific to the intended population

• Specific to the characteristics of the conditions or disease treated

• Specific to the intended population

• Specific to the characteristics of the conditions or disease treated



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

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


Document, document, document!Document, document, document!Document, document, document!Document, document, document!

• Development of instrument–Patient involvement–Population–Goals

• Validation of instrument–Format, wording–Cultural issues, multinational

studies–Drug intervention studies

• Development of instrument–Patient involvement–Population–Goals

• Validation of instrument–Format, wording–Cultural issues, multinational

studies–Drug intervention studies



• Concepts: what will be measured

Examples:–Pain severity–Psychological function–Physical function

• Concepts: what will be measured

Examples:–Pain severity–Psychological function–Physical function



• Domain: Q concept Examples:–PFSF: Desire, Responsiveness,

Disinterest–Physical function: symptom

improvement, physical abilities, ADL

• Domain: Q concept Examples:–PFSF: Desire, Responsiveness,

Disinterest–Physical function: symptom

improvement, physical abilities, ADL



• Clinically meaningful difference–Prospective plan–Patient involvement

• Planned use in clinical study–Primary evidence for efficacy–“Value-added”

• Intended population

• Clinically meaningful difference–Prospective plan–Patient involvement

• Planned use in clinical study–Primary evidence for efficacy–“Value-added”

• Intended population



• Implementation–Training and instructions–Format

• Implementation–Training and instructions–Format


Trial Design IssuesTrial Design IssuesTrial Design IssuesTrial Design Issues

• Prospectively defined• Blinding• Use of instrument–Standardized instructions–Standardized training–Training and blinding of

interviewers–Recall to baseline

• Prospectively defined• Blinding• Use of instrument–Standardized instructions–Standardized training–Training and blinding of

interviewers–Recall to baseline


Trial Design IssuesTrial Design IssuesTrial Design IssuesTrial Design Issues

• Data capture–Paper–Electronic

• Data capture–Paper–Electronic


Role of PRO as an endpointRole of PRO as an endpointRole of PRO as an endpointRole of PRO as an endpoint

• Primary evidence of efficacy• “Value-added”–Pre-specify–Report findings, regardless of

statistical significance and direction

• Primary evidence of efficacy• “Value-added”–Pre-specify–Report findings, regardless of

statistical significance and direction


Analysis PlanAnalysis PlanAnalysis PlanAnalysis Plan

• Missing data–Entire instruments–Domains– Items–Visits

• Multiple endpoints

• Missing data–Entire instruments–Domains– Items–Visits

• Multiple endpoints


And finally … Labeling!And finally … Labeling!And finally … Labeling!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

• Well-controlled studies• Instrument reliably and validly

measures the concepts claimed• Convey both positive and negative

effects• Specific to the concept measured


SummarySummarySummarySummary

• Start early in clinical development program

• Talk to FDA review divisions• Document, document, document–Development of instrument–Validation of instrument–Clinically meaningful difference– Implementation

• Start early in clinical development program

• Talk to FDA review divisions• Document, document, document–Development of instrument–Validation of instrument–Clinically meaningful difference– Implementation



• Study Design–Blinding–Use of instrument–Prospectively defined

• Analysis plan

• Study Design–Blinding–Use of instrument–Prospectively defined

• Analysis plan



• Labeling –Conveys both negative and

positive effects–Specificity to concepts measured

• Labeling –Conveys both negative and

positive effects–Specificity to concepts measured

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

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