PF731 A STRATEGY FOR THE MEASUREMENT OF SICKLE CELL DISEASE SYMPTOMS FROM THE PATIENT PERSPECTIVE
Authors: Ojo F. , Litcher‐Kelly L. , Mazar I. , Klooster B. , Roeder A. , Chaston E. , Ollis S. , Treadwell M. , Reasner D. 
Published: June 2019

Please indicate where the abstract has been published before: Blood 2018Background:Sickle cell disease (SCD), an inherited blood disorder, impacts multiple organs leading to variable clinical presentation. In addition to severe pain episodes, patients may experience chronic symptoms (eg, pain, tiredness). Assessing treatment benefit using a patient‐reported outcome (PRO) measurement strategy is important in SCD research.Aims:To understand the SCD patient experience and inform the selection or development of fit‐for‐purpose PRO instrument(s) to assess daily chronic symptoms in clinical trials for adolescents and adults with SCD ≥16 years.Methods:A literature review and interviews with clinical experts (N = 5) and adolescents and adults with SCD (N = 20) were conducted to develop an SCD conceptual model summarizing important SCD signs, symptoms, and impacts. An instrument review identified and assessed the existing PRO measures used in SCD research and documented their development history and measurement properties. Concepts in the SCD conceptual model were compared to those assessed in reviewed PRO measures. Considerations for concept selection (eg, suitability of measuring symptoms via PRO measure) and item construction (eg, selection of recall period) in developing PRO measurement strategies were summarized.Results:Patients reported 22 symptoms that they experienced regularly and/or during pain crises, which were largely endorsed by the literature and/or clinical experts. Pain was reported by all patients, and tiredness was reported by 80%; both were reported as the most important to improve with treatment. Patients reported impacts of SCD on their daily lives across 9 domains (activities of daily living, cognitive, emotional, financial, leisure, physical, sleep, social, and work/school impacts).Five PRO measures used in SCD research were reviewed: The Adult Sickle Cell Quality of Life Measurement Information System (ASCQ‐MeSM), Pediatric Quality of Life Inventory (PedsQL™) sickle cell disease module, the Patient‐Reported Outcomes Measurement Information System (PROMIS) Fatigue and Pediatric Pain Interference measures, and Scribe Sickle Cell Record of Daily Symptom Burden™ (SSCRDSB). None of the measures assessed >5 of the symptoms included in the SCD conceptual model, with the SSCRDSB assessing the greatest number (5/22 concepts). Pain was the most frequently measured concept (assessed by 3/5 PRO measures). The most frequently measured impact domain was physical impacts, assessed to varying degrees by all 5 measures. The PedsQL™ SCD module assessed the greatest number of impact domains in the SCD conceptual model (7/9 domains). The reviewed measures were determined to have limitations (eg, inadequate concept coverage and recall period) in assessing SCD symptoms daily as part of regulated clinical trials.Summary/Conclusion:These results suggest that 1) patients experience several SCD symptoms regularly and intermittently, 2) existing instruments, while perhaps suitable for other contexts of use or in conjunction with other tools, may be inadequate for evaluating important SCD symptoms in a way that can demonstrate treatment benefit when measured daily in regulated clinical research. Instruments developed for this purpose should have documented evidence of content validity (ie, relevant instrument measures and understandable concepts) and should include clear instructions, a short recall period, items that measure dimensions of importance to patients (eg, symptom intensity), and well‐defined response options that are sufficiently sensitive to detect change.