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

Abstract

Background Patient-reported outcome measures (PROs) used to measure symptoms of patients with paroxysmal nocturnal hemoglobinuria (PNH) in trials do not measure PNH symptoms comprehensively and do not assess daily fluctuations in symptoms. Following a literature review and consultation with a PNH expert, we drafted the PNH Symptom Questionnaire (PNH-SQ) and a patient-centric conceptual model of PNH symptoms and impacts. We then interviewed 15 patients with PNH to assess comprehensiveness of symptom capture from the patient perspective and to cognitively debrief the PNH-SQ. Patient interview data were also used to finalize the PNH conceptual model. Results Participants mentioned 27 signs or symptoms of PNH spontaneously or after being probed; 93% reported experiencing ≥ 1 PNH symptom. Concept saturation was reached for all PNH symptoms. Further, interviews confirmed the instrument captured the most common PNH symptoms, including fatigue (87%), abdominal pain (60%), and difficulty swallowing (47%), with fatigue ranked as the most bothersome symptom. The interviews demonstrated that participants understood the items of the PNH-SQ (90–100%); considered the symptoms relevant (> 50– > 90%); the recall period appropriate (> 80–100%); and the response options suitable (> 80–100%). Participants also suggested changes regarding item redundancy and relevance; this feedback was used to finalize the instrument. Conclusions The finalized PNH-SQ assesses the presence and severity of 10 symptoms—abdominal pain, chest discomfort, difficulty sleeping, difficulty swallowing, difficulty thinking clearly, fatigue, headache, muscle weakness, pain in the legs or back, and shortness of breath—over 24 h. The PNH-SQ is a content-valid questionnaire suitable for assessing daily symptom presence and severity in PNH clinical trials.

The burden of illness of patients with paroxysmal nocturnal haemoglobinuria receiving C5 inhibitors in France, Germany and the United Kingdom: Patient‐reported insights on symptoms and quality of life

“…Real-world sampling of patients prescribed ravulizumab was only possible in Germany, and results were not adjusted for differing patient characteristics. Interpretation of treatment durations should account for the possibility of recall errors and the lack of data on previous treatment switching.Although validated in a PNH population, the EORTC QLQ-C30 questionnaire was developed for patients with cancer (PNH-specific HRQoL tools were still in development at the time)46,47 ; there is currently no MCID for EORTC QLQ-C30 validated for PNH. The validity of WPAI self-reported results is less robust than that of interviewerproctored results,25 and to our knowledge, our application to patients with PNH is novel and not clinically validated.…”

Predictors for improvement in patient-reported outcomes: post hoc analysis of a phase 3 randomized, open-label study of eculizumab and ravulizumab in complement inhibitor-naive patients with paroxysmal nocturnal hemoglobinuria

“…More recently, disease-specific tools for assessing QoL and PROs in PNH have been developed including the Quality of Life Questionnaire for AA and PNH (QLQ-AA/PNH) and the PRO questionnaire for AA and PNH (PRO-AA/PNH) [ 28 , 29 ]. The PNH Symptom Questionnaire (PNH-SQ) has been developed to assess daily PNH symptoms of patients [ 30 ]. However, further validation of PRO-AA/PNH and determination of the psychometric properties of QLQ-AA/PNH and PNH-SQ are required [ 28 – 30 ].…”

“…The PNH Symptom Questionnaire (PNH-SQ) has been developed to assess daily PNH symptoms of patients [ 30 ]. However, further validation of PRO-AA/PNH and determination of the psychometric properties of QLQ-AA/PNH and PNH-SQ are required [ 28 – 30 ].…”

Managing Fatigue in Patients with Paroxysmal Nocturnal Hemoglobinuria: A Patient-Focused Perspective

“…The PNH-SQ (Symptom Questionnaire) is a novel questionnaire evaluating the presence and severity of 10 PNH-related symptoms over 24 hours. 48 Moreover, a PNH/aplastic anemia (AA) specific QoL questionnaire has been created as a specific disease PRO measure, although psychometric evaluations are still undergoing. 49 Lastly, PNH Patient Preference Questionnaire (PNH-PPQ), a 11-item questionnaire, has been validated to assess patients’ preferences in the context of the clinical trials comparing eculizumab with its long half-life analogue ravulizumab.…”