PSY45 PATIENT-REPORTED OUTCOMES USED IN CLINICAL TRIALS OF SYSTEMIC LUPUS ERYTHEMATOSUS: A REVIEW OF SUITABILITY FOR FDA LABELLING CLAIMS

Abstract

This review sought to identify patient-reported outcome (PRO) instruments that have been used in clinical trials of systemic lupus erythematosus (SLE) and examine their suitability for FDA labelling claims, based on proximity of the concept they measure to symptoms of SLE and evidence of content validity in SLE patients. A search was conducted on clinicaltrials.gov to identify PROs used as primary and/or secondary endpoints in SLE clinical trials. A literature review of identified PROs was then conducted, examining their structure, the concept they measure and evidence of content validity as per FDA standards, including involvement of SLE patients in instrument development. 49 different PRO instruments, used across 129 trials, were identified. The majority (39) measured multi-dimensional constructs or distal concepts of disease, including health-related quality of life (HRQOL), impacts on mental function (depression, anxiety, stress, anger), cognition, physical activity, sleep, social functioning and work performance, as well as self-management/efficacy, coping strategies and global impression of change. 10 identified PROs measured proximal concepts/symptoms of disease, namely fatigue and pain. Out of all 49 instruments that were identified, only 4 PROs, all HRQOL instruments, were SLE-specific and three of those, the LupusQoL, LupusPro and SLEQOL, had satisfactory evidence of content validity. A further review of these three instruments revealed that only LupusQOL contained domains that measure well-defined and proximal concepts/symptoms of disease, namely pain and fatigue. Despite a considerable number of PROs that have been used in SLE clinical trials, only three instruments had satisfactory evidence of content validity in SLE patients in line with FDA standards. Only one of these instruments, the LupusOOL, contains domains measuring proximal concepts/symptoms of disease (pain and fatigue) that could be considered suitable for inclusion in endpoint models in SLE drug development with intended PRO-based labelling claims in the US.