A Systematic Literature Review of Patient-Reported Outcome Instruments Used in Sickle Cell Disease

Abstract

Introduction: Patients with sickle cell disease (SCD) often have recurrent episodes of acute severe pain (vaso-occlusive crises, VOCs), which result in repeated hospital admissions and use of pharmacological treatments, and can negatively impact patients' health-related quality of life (HRQL). Most SCD randomized clinical trials (RCTs) are designed to evaluate efficacy in relation to changes in the number of VOCs and their impact on HRQL. We conducted a systematic literature review (SLR) to identify patient-reported outcome (PRO) and healthcare resource utilization (HCRU) instruments used in RCTs and real-world studies and to evaluate their psychometric properties with a view to provide recommendations of appropriate PRO endpoints for use in clinical trials for SCD treatments in the United States (US).Methods: An SLR was conducted to search, identify and summarize validated PRO instruments that have been used by patients with SCD in the US and their caregivers. MEDLINE and EMBASE were searched using terms synonymous with “sickle cell disease” and “psychometric properties” of PRO instruments for articles published in English between 1997 and March 2017 focusing on pediatric patients (5-17 years) and their caregivers, and adults (≥18 years). Studies were included if results were based on assessing psychometric properties of PRO instruments and if the studies were interventional or observational in design. Exclusion criteria included studies conducted in non-US populations, reporting on non-validated generic questionnaires or without any psychometric data. Conference abstracts, narrative reviews, letters to the editor, laboratory studies and case reports/series were excluded. The quality of PRO instruments in the included studies was assessed using the COnsensus-based Standards for the selection of health Measurement INstruments (COSMIN) checklist, a well-established checklist to measure the methodological quality and performance of PRO instruments across a number of domains as reported in psychometric evaluation studies.Results: The SLR identified 504 references for title/abstract screening. Of these, 46 full-text articles were further assessed for inclusion and 19 articles were included. Two additional articles were identified from manual reference checks of relevant SLRs. Thus, a total of 21 US-based studies assessing 10 child and 15 adult PRO instruments in SCD were included in the review. No validated PRO instruments were found that measured caregiver burden in SCD and no validated HCRU instruments for any SCD population were identified. The review of pediatric studies identified the most commonly reported instrument to be the Pediatric Quality of Life Inventory (PedsQL), while most of the adult instruments (9 of 15) focused on evaluating self-efficacy/-esteem and pain in relation to SCD. Only one instrument, the Adult Sickle Cell Quality of Life Measurement (ASCQ-Me), was identified as evaluating HRQL in adults. Out of the 25 PRO instruments reviewed for both children and adults, only 3 out of 10 and 5 out of 15 instruments, respectively, were specifically developed for these age groups with SCD. There were little or no data on validation conducted in SCD development cohorts for most instruments. Additionally, the included studies did not assess minimally important differences in any of the instruments reviewed. In terms of instruments' psychometric properties, most instruments (9 of 15) identified for adult populations had strong internal reliability; however, there was often insufficient information to assess the content validity, construct validity, responsiveness and test-retest reliability of the instruments identified for both child and adult populations.Conclusions: Limited evidence on the psychometric properties of PRO instruments used in patients with SCD was identified. Furthermore, among the instruments reviewed, none was found to sufficiently capture all the PRO aspects of SCD and its complications on patients' HRQL for use as key trial endpoints. Further research should validate, or develop if no instrument is in existence, PRO instruments to assess HRQL of patients with SCD, PRO instruments for caregivers and HCRU instruments. DisclosuresSarri:Evidera: Employment. Bhor:Novartis: Employment, Equity Ownership, Research Funding. Abogunrin:Evidera: Consultancy; Novartis: Research Funding. Farmer:Evidera: Employment; Novartis: Research Funding. Nandal:Novartis: Employment, Equity Ownership, Research Funding. Revicki:Novartis: Consultancy, Research Funding.