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

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

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

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

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

To support a PRO claim • Reliable and valid instrument • Instrument measures concepts claimed • Instrument measures impact of an intervention • Well-controlled investigations

Early in product development • Identify endpoints • Identify desired claims • Discuss with FDA

Selection of PRO Instrument • Measures the claimed treatment benefit from the patient’s perspective • Measures both the positive and negative benefits of the intervention

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

Selection of PRO Instrument • Three possible choices • Existing instrument • Modification of existing instrument • New instrument

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

Document, document, document! • Concepts: what will be measuredExamples: • Pain severity • Psychological function • Physical function

Document, document, document! • Domain: Q conceptExamples: • PFSF: Desire, Responsiveness, Disinterest • Physical function: symptom improvement, physical abilities, ADL

Document, document, document! • Clinically meaningful difference • Prospective plan • Patient involvement • Planned use in clinical study • Primary evidence for efficacy • “Value-added” • Intended population

Document, document, document! • Implementation • Training and instructions • Format

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

Trial Design Issues • Data capture • Paper • Electronic

Role of PRO as an endpoint • Primary evidence of efficacy • “Value-added” • Pre-specify • Report findings, regardless of statistical significance and direction

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

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

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

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

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

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