Interpreting change from patient reported outcome (PRO) endpoints: patient global ratings of concept versus patient global ratings of change, a case study among osteoporosis patients.

Annabel Nixon,Russel Burge,Helen Doll,Cicely Kerr,April N Naegeli

doi:10.1186/s12955-016-0427-5

Annabel Nixon, Russel Burge + Show 3 more

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https://doi.org/10.1186/s12955-016-0427-5

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Abstract

BackgroundRegulatory guidance recommends anchor-based methods for interpretation of treatment effects measured by PRO endpoints. Methodological pros and cons of patient global ratings of change vs. patient global ratings of concept have been discussed but empirical evidence in support of either approach is lacking. This study evaluated the performance of patient global ratings of change and patient global ratings of concept for interpreting patient stability and patient improvement.MethodsPatient global ratings of change and patient global ratings of concept were included in a psychometric validation study of an osteoporosis-targeted PRO instrument (the OPAQ-PF) to assess its ability to detect change and to derive responder definitions. 144 female osteoporosis patients with (n = 37) or without (n = 107) a recent (within 6 weeks) fragility fracture completed the OPAQ-PF and global items at baseline, 2 weeks (no recent fracture), and 12 weeks (recent fracture) post-baseline.ResultsResults differed between the two methods. Recent fracture patients reported more improvement while patients without recent fracture reported more stability on ratings of change than ratings of concept. However, correlations with OPAQ-PF score change were stronger for ratings of concept than ratings of change (both groups). Effect sizes for OPAQ-PF score change increased consistently with level of change in ratings of concept but inconsistently with ratings of change, with the mean AUC for prediction of a one-point change being 0.72 vs. 0.56.ConclusionsThis study provides initial empirical support for methodological and regulatory recommendations to use patient global ratings of concept rather than ratings of change when interpreting change captured by PRO instruments in studies evaluating treatment effects. These findings warrant being confirmed in a purpose-designed larger scale analysis.Electronic supplementary materialThe online version of this article (doi:10.1186/s12955-016-0427-5) contains supplementary material, which is available to authorized users.

Highlights

Regulatory guidance recommends anchor-based methods for interpretation of treatment effects measured by patient reported outcome (PRO) endpoints
The debate heightened during the consultation period following publication of the Food and Drug Administration (FDA) draft guidance [5] and continued after the publication of the FDA final guidance report for Industry PRO measures [2], with Burke and Trentacosti [6] offering further considerations beyond those provided in the final FDA guidance
The minimum important difference (MID) is the amount of difference between treatment groups in the change observed in a PRO measure that can be interpreted as a treatment benefit [5], whereas the responder definition is the amount of change in an individual patient which can be interpreted as a treatment benefit: the proportions of individuals in each trial arm who meet this threshold for PRO score change are compared between treatment arms

Summary

Introduction

Regulatory guidance recommends anchor-based methods for interpretation of treatment effects measured by PRO endpoints. This study evaluated the performance of patient global ratings of change and patient global ratings of concept for interpreting patient stability and patient improvement. As with all outcome measures used to evaluate the impact of a medical product, one of the biggest challenges for patient reported outcome (PRO) endpoints is how to interpret the change in scores between two time points or the difference in change scores between treatment groups [1]. A key shift in approach over this period has been a move away from using the group level minimum important difference (MID) to evaluate treatment benefit, the focus of much of the prior efforts to develop values to aid interpretation of change [4], to using the patient level responder definition. The MID is the amount of difference between treatment groups in the change observed in a PRO measure that can be interpreted as a treatment benefit [5], whereas the responder definition is the amount of change in an individual patient which can be interpreted as a treatment benefit: the proportions of individuals in each trial arm who meet this threshold (or a variety of thresholds) for PRO score change are compared between treatment arms

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