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 AA/PNH-specific questionnaires 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, AA/PNH-specific patient-reported outcome (PRO) questionnaires including the selected measures were designed (Phase III). Results AA symptoms from 62 and PNH symptoms from 45 observational studies 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. Therefore, patient- as well as expert-centered PRO questionnaires in AA and PNH were created following the concepts of validated instruments. Conclusion The development of symptom self-reporting questionnaires for AA and PNH was feasible and the disease-specific PRO questionnaires can now be validated within a web-based workflow in a subsequent feasibility study.

Changes in hemoglobin and clinical outcomes drive improvements in fatigue, quality of life, and physical function in patients with paroxysmal nocturnal hemoglobinuria: post hoc analyses from the phase III PEGASUS study

“…The EORTC QLQ-C30 and the FACIT-F were originally developed for use in evaluations of HRQoL among people with cancer, with their validity extended to people with PNH. Other PRO questionnaires are available for patients with PNH that encompass additional aspects of the disease [ 37 , 38 ]. Potential collection mode-related and non-response biases may have been introduced.…”

Core set of patient-reported outcomes for myelodysplastic syndromes: an EUMDS Delphi study involving patients and hematologists

“…53 Differences in PRO prioritization between patients and physicians have also been observed in other comparable studies. Weisshaar et al 54 found substantial variations in ratings between patients and physicians, in a study for PRO selection in aplastic anemia and paroxysmal nocturnal hemoglobinuria. Issues related to QoL (e.g., mood disturbances, fatigue and impaired activities of daily living) were rated higher by patients than by hematologist experts, who prioritized physical constraints (e.g., bleeding, fever, hemoglobinuria).…”

A novel patient-reported outcome instrument assessing the symptoms of paroxysmal nocturnal hemoglobinuria, the PNH-SQ

“…Recently, the patient-reported outcome questionnaire for aplastic anemia and paroxysmal nocturnal hemoglobinuria (PRO-AA/PNH) was developed [23]. However, upon comparison of the measures, only some of the 10 PNH-SQ items are also measured in the PRO AA/PNH (e.g., fatigue, shortness of breath, difficulty concentrating, and dysphagia).…”