OBJECTIVES: A Core Outcome Set (COS) for Sickle Cell Disease (coreSCD) has been suggested by an expert panel using Core Outcome Measures in Effectiveness Trials (COMET) Initiative methodology (Tambor et al. 2021). This is an empirical study investigating whether registered clinical trials conform to coreSCD.

METHODS: Clinicaltrials.gov, searched for on-going and recently completed clinical trials (Nov-2015 to Nov-2022), and PROLABELS™ database, were used to obtain information on Patient-Reported Outcomes (PROs). The findings were tabulated in a conceptual framework and compared with coreSCD in terms of alignment of key concepts. Additionally, a list of measures used for each concept was reported.

RESULTS: A total of 173 trials were retrieved, of which 54 included PRO. A total of 90 unique PRO measures were identified. The top 3 concepts assessed were: pain (mostly intensity), Health-Related Quality of Life (HRQOL) and Fatigue/Tiredness/Sleep impact. Majority of PROs were secondary endpoints. Considering the PROs included within coreSCD (“Pain frequency”, “HRQOL” and “Ability to return to usual activities” (AtR)), only HRQOL was extensively assessed (59%), while Pain frequency and AtR were less frequently assessed (4% and 6%, respectively). No trials included all three outcomes as endpoints on Clinicaltrials.gov. We identified one potential measure to assess pain frequency and several for HRQOL. However, only diaries for pain assessment have been accepted in labels by FDA and EMA.

CONCLUSIONS: Empirical review of PROs used in clinical trials and labeling claims and comparison of the findings with experts recommended COS can identify patient outcomes that have not been the focus of study as primary or secondary endpoints, and potentially lack of evidence for scientifically driven treatment options. Moreover, review of trials identified a list of possible measures to assess SCD COS. Nevertheless, only one measure was included in labels, suggesting the need for further evaluation of fit-for-purpose instruments.