Development of a patient-reported outcome questionnaire for aplastic anemia and paroxysmal nocturnal hemoglobinuria (PRO-AA/PNH)

Abstract

Background: The introduction of new therapy modalities has significantly improved the outcome of aplastic anemia (AA) and paroxysmal nocturnal hemoglobinuria (PNH) patients. However, relatively little is known about the exact disease burden of AA/PNH since standardized assessments of symptoms including health-related quality of life (HRQoL) are frequently missing or inadequately designed for this rare patient group. We aimed to develop an AA/PNH-specific questionnaire for self-reporting of symptoms, which could be included in electronic platforms for data collection and patient care. Methods: By scoping review, we extracted any reported symptoms in AA/PNH and their prevalence from the literature (Phase I). Consensus rounds with patients and medical experts were conducted to identify core symptoms reported in the literature and to add missing items (Phase II). Ultimately, an AA/PNH-specific patient-reported outcome (PRO) questionnaire including the selected measures was designed (Phase III). Results: Sixty-one symptoms in AA and 45 symptoms in PNH were extracted from the literature. Twenty-four patients and seven medical experts identified 11 core symptoms including HRQoL issues after three consensus rounds. Significant differences in the symptom ranking of patients versus medical experts could be observed. We determined a compromise between experts’ opinions on physical constraints and patients’ frequent demands on HRQoL. These items built the basis for the development of two PRO questionnaires separate for AA and PNH following the concepts of validated instruments. Conclusion: The development of a symptom self-reporting questionnaire for AA and PNH was feasible and the PRO questionnaire can now be validated within a web-based workflow in a subsequent feasibility study.