TY - JOUR
T1 - Clinical outcome event adjudication in a 10-year prospective study of nucleos(T)ide analogue therapy for chronic hepatitis b
AU - Lim, Joseph K.
AU - Chang, Alex Y.
AU - Zaman, Atif
AU - Martin, Paul
AU - Fernandez-Rodriguez, Conrado M.
AU - Korkmaz, Mete
AU - Rossi, Simona
AU - Ford, James M.
AU - Noonan, Tamara
AU - Cooney, Elizabeth
AU - Navarro, Victor
AU - Colombato, Luis
N1 - Funding Information:
Editorial support was provided by R Boehme of Articulate Science and funded by Bristol-Myers Squibb. Operational and pharmacovigilance support was provided by Pharmaceutical Product Development (PPD), LLC. This study was funded by Bristol-Myers Squibb, which designed the study, conducted statistical analyses, and provided financial support for the study.
Publisher Copyright:
© 2020 Authors.
PY - 2020
Y1 - 2020
N2 - Background and Aims: In the REALM (Randomized, Obser-vational Study of Entecavir to Assess Long-Term Outcomes Associated with Nucleoside/Nucleotide Monotherapy for Patients 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 progression events, and deaths. An external event adjudication committee (EAC) was convened to provide real-time review of reported COEs to optimize data quality, and minimize potential adverse effects of the large cohort, interdisciplinary outcome assessments, geographic scope, and long duration. Methods: The EAC comprised an international group of hepatologists and oncologists with expertise in diagnosis of targeted COEs. The EAC reviewed and adjudicated COEs according to prospectively defined diagnostic criteria captured in the EAC charter. Operational processes, including data 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 carcinoma (HCC), 83.3%; non-HCC malignancies, 88.0%; non-HCC HBV disease progression, 68.2%. Reasons for lack of concordance 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 consistency; EAC performance was facilitated by well-defined diagnostic criteria, effective data capture, and efficient operational processes. Trial registration: ClinicalTrials.gov NCT00388674.
AB - Background and Aims: In the REALM (Randomized, Obser-vational Study of Entecavir to Assess Long-Term Outcomes Associated with Nucleoside/Nucleotide Monotherapy for Patients 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 progression events, and deaths. An external event adjudication committee (EAC) was convened to provide real-time review of reported COEs to optimize data quality, and minimize potential adverse effects of the large cohort, interdisciplinary outcome assessments, geographic scope, and long duration. Methods: The EAC comprised an international group of hepatologists and oncologists with expertise in diagnosis of targeted COEs. The EAC reviewed and adjudicated COEs according to prospectively defined diagnostic criteria captured in the EAC charter. Operational processes, including data 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 carcinoma (HCC), 83.3%; non-HCC malignancies, 88.0%; non-HCC HBV disease progression, 68.2%. Reasons for lack of concordance 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 consistency; EAC performance was facilitated by well-defined diagnostic criteria, effective data capture, and efficient operational processes. Trial registration: ClinicalTrials.gov NCT00388674.
KW - Antiviral therapy
KW - Clinical outcomes
KW - Event adjudicationLiver cirrhosis
KW - Hepatitis B
UR - http://www.scopus.com/inward/record.url?scp=85099068271&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85099068271&partnerID=8YFLogxK
U2 - 10.14218/JCTH.2020.00039
DO - 10.14218/JCTH.2020.00039
M3 - Article
AN - SCOPUS:85099068271
SN - 2225-0719
VL - 8
SP - 377
EP - 384
JO - Journal of Clinical and Translational Hepatology
JF - Journal of Clinical and Translational Hepatology
IS - 4
ER -