摘要
Background and Aims:In the REALM (Randomized, Obser-vational Study of Entecavir to Assess Long-Term Outcomes Associated with Nucleoside/Nucleotide Monotherapy for Pa-tients with Chronic HBV Infection) study, 12,378 patients with chronic hepatitis B virus (HBV) infection received up to 10 years of randomized therapy with entecavir or another HBV nucleos(t)ide analogue. Monitored clinical outcome events (COEs) included malignant neoplasms, HBV disease progres-sion events, and deaths. An external event adjudication com-mittee (EAC) was convened to provide real-time review of reported COEs to optimize data quality, and minimize poten-tial adverse effects of the large cohort, interdisciplinary out-come assessments, geographic scope, and long duration. Methods:The EAC comprised an international group of hep-atologists and oncologists with expertise in diagnosis of tar-geted COEs. The EAC reviewed and adjudicated COEs according to prospectively defined diagnostic criteria cap-tured in the EAC charter. Operational processes, including da-ta collection and query procedures, were implemented to optimize efficiency of data recovery to maximize capture of adjudicated COEs, the primary study outcome measure. Results: A total of 1724 COEs were reported and 1465 of these events were adjudicated by the EAC as reported by the investigators (85.0% overall concordance). Concordance by COE type varied: deaths, 99.6%;hepatocellular carcino-ma (HCC), 83.3%;non-HCC malignancies, 88.0%;non-HCC HBV disease progression, 68.2%. Reasons for lack of con-cordance were most commonly lack of adequate supporting data to support an adjudicated diagnosis or evidence that the event pre-dated the study. Conclusions: The REALM EAC performed a critical role in ensuring data quality and consis-tency;EAC performance was facilitated by well-defined diag-nostic criteria, effective data capture, and efficient operational processes. Trial registration: ClinicalTrials.gov NCT00388674.
基金
This study was funded by Bristol-Myers Squibb,which designed the study,conducted statistical analyses,and provided financial support for the study.
