Development of a Patient-Reported Outcome Measure for Hypereosinophilic Syndrome.

Abstract

Although a phase 3 double-blind, placebo-controlled registration trial of mepolizumab for hypereosinophilic syndromes (HES) used a patient-reported severity assessment, no patient reported outcome (PRO) measures have been formally developed for HES. Prior attempts to develop a PRO have been unsuccessful. The purpose of this study was to develop an outcome measure using accepted approaches for qualitative methods, conceptual models, and analyses to detect symptom severity and patient experience of disease activity. The study was performed using U.S. Food and Drug Administration guidance for development of symptom scales for outcome metrics using psychometric analysis and patient-administered questionnaires. Sixty-three heterogeneous patients with different HES subtypes enrolled on a natural history study of eosinophilia were invited to participate. All participants provided informed consent. At baseline, patients filled out an HES Symptom Inventory (HES-SI) and indicated up to 4 of their most bothersome symptoms (HES-MBS). Symptom fluctuation was recorded over the course of 3 months, and clinical metrics (treatment changes) were assessed during the same period. Across all timepoints, strong statistically significant correlations were observed for the HES-SI total score (r = 0.69-0.80; P < .0001) and HES-MBS score (r = 0.71-0.81; P < .0001) with the patients' perception of disease status (Patient Global Assessment). The HES-SI and HES-MBS showed sensitivity to change and demonstrated test-retest reliability. Analyses of the HES-SI and HES-MBS scores provided strong preliminary evidence supporting the reliability and validity of these measures for use in future HES clinical trials. The ability of these scales to accurately measure changes in HES symptoms with successful treatment requires further study.