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.
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.
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.
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.
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Asthma Quality of Life Questionnaire
Cumulative distribution function
Chronic Heart Failure Questionnaire
Chronic Respiratory Questionnaire
Eastern Cooperative Oncology Group
Food and drug administration
Industry Advisory Committee
International Society for Quality of Life Research
Minimal clinically important difference
Minimal important difference
Quality of life
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Members of the Industry Advisory Committee (IAC), the Board of Directors of the International Society for Quality of Life Research (ISOQOL), and two anonymous reviewers offered valuable suggestions that were incorporated into this paper.
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Wyrwich, K.W., Norquist, J.M., Lenderking, W.R. et al. Methods for interpreting change over time in patient-reported outcome measures. Qual Life Res 22, 475–483 (2013). https://doi.org/10.1007/s11136-012-0175-x
- Patient-reported outcome
- Change over time
- Quality of life
- Cumulative distribution function
- Minimal important difference
- Responder definition