title: Methods for interpreting change over time in patient-reported outcome measures.
abstract: OBJECTIVE
  Interpretation guidelines are needed for patient-reported outcome (PRO) measures' change scores to evaluate efficacy of an intervention and to communicate PRO results to regulators, patients, physicians, and providers. The 2009 Food and Drug Administration (FDA) Guidance for Industry Patient-Reported Outcomes (PRO) Measures: Use in Medical Product Development to Support Labeling Claims (hereafter referred to as the final FDA PRO Guidance) provides some recommendations for the interpretation of change in PRO scores as evidence of treatment efficacy.
  
  
  METHODS
  This article reviews the evolution of the methods and the terminology used to describe and aid in the communication of meaningful PRO change score thresholds.
  
  
  RESULTS
  Anchor- and distribution-based methods have played important roles, and the FDA has recently stressed the importance of cross-sectional patient global assessments of concept as anchor-based methods for estimation of the responder definition, which describes an individual-level treatment benefit. The final FDA PRO Guidance proposes the cumulative distribution function (CDF) of responses as a useful method to depict the effect of treatments across the study population.
  
  
  CONCLUSIONS
  While CDFs serve an important role, they should not be a replacement for the careful investigation of a PRO's relevant responder definition using anchor-based methods and providing stakeholders with a relevant threshold for the interpretation of change over time.
authors.affiliation: United BioSource Corporation, 7101 Wisconsin Avenue, Suite 600, Bethesda, MD 20814, USA. kathy.wyrwich@unitedbiosource.com
authors.forename: K W
authors.initials: KW
authors.lastname: Wyrwich
authors.forename: J M
authors.initials: JM
authors.lastname: Norquist
authors.forename: W R
authors.initials: WR
authors.lastname: Lenderking
authors.forename: S
authors.initials: S
authors.lastname: Acaster
mesh_terms: D002986:Clinical Trials as Topic; D003627:Data Interpretation, Statistical; D006801:Humans; D007391:International Cooperation; D017063:Outcome Assessment, Health Care / Q000379:methods*; D017060:Patient Satisfaction; D017410:Practice Guidelines as Topic; D011788:Quality of Life; D013997:Time Factors; D014481:United States; D014486:United States Food and Drug Administration