A Novel Patient Reported Outcome Instrument Assessing the Symptoms of Paroxysmal Nocturnal Hemoglobinuria

• Published in: Blood 2019-11, Vol.134 (Supplement_1), p.385-385
• Main Authors: Daly, R Paola, Jalbert, Jessica J, Keith, Shannon, Symonds, Tara, Shammo, Jamile M.
• Format: Article
• Language: English
• ISSN: 0006-4971; 1528-0020
• DOI: 10.1182/blood-2019-125844

Introduction. Paroxysmal nocturnal hemoglobinuria (PNH) is a rare, acquired, life-threatening blood disease. Frequently reported symptoms of PNH are fatigue, dyspnea, hemoglobinuria, abdominal pain, and chest pain. While PNH-related symptoms can impact quality of life, there are no patient-reported outcome (PRO) measures that assess daily occurrence and severity of PNH-specific symptoms. The objective of this study was to gain a deeper understanding of the patient experience related to symptoms of PNH, and to assess the content validity of the newly developed PNH Symptom Questionnaire (PNH-SQ). Methods. The content and design of the PNH-SQ was informed by a review of the empirical literature, review of COAs used in registrational PNH trials to assess symptoms and impacts of PNH, and through discussions with physicians who have experience treating patients with PNH. The first draft of the PNH-SQ allowed the patient to record, on a daily basis, the presence/absence of 12 symptoms in the past 24 hours (fatigue; shortness of breath; muscle weakness; headache; abdominal pain; leg/back pain; chest discomfort; sexual difficulties; difficulty sleeping; difficulty focusing; difficulty thinking clearly; difficulty swallowing), and the severity of each symptom using a 5-point Likert scale. Trained interviewers conducted telephone, video, or in-person qualitative, semi-structured 60-minute interviews with adult patients with a clinician-confirmed PNH diagnosis. The interviews consisted of two distinct parts: concept elicitation (CE), to assess whether the PNH-SQ captured all important symptoms from the perspective of the patient; and cognitive debriefing (CD), to evaluate the patient's ability to understand and respond to the PNH-SQ. During CE, participants discussed symptoms and impacts of PNH. This was followed by CD, in which participants reviewed and completed the PNH-SQ and asked about each part of the PNH-SQ including the instructions, understanding and relevance of items, recall period, and response options. Interviews were audio-recorded, transcribed, coded, and analyzed. Revisions to the PNH-SQ were considered after interviews were completed and analyzed. Results. A total of 15 participants (mean age of 42.8 years; 53.3% women) from across the United States were interviewed; participants had a mean of 13.4 years since PNH diagnosis, and 66.7%, 13.3%, and 20.0% self-reported very mild/mild, moderate, and severe/very severe PNH, respectively. In the CE part of