Journal of Clinical and Translational Hepatology

Journal of Clinical and Translational Hepatology

Monday, 03 / 08 / 2021

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Clinical Outcome Event Adjudication in a 10-Year Prospective Study of Nucleos(t)ide Analogue Therapy for Chronic Hepatitis B

Joseph K Lim*,1 , Alex Y Chang2Atif Zaman3Paul Martin4Conrado M Fernandez-Rodriguez5Mete Korkmaz6, Simona Rossi7, James M Ford8Tamara Noonan9Elizabeth Cooney9Victor Navarro7Luis Colombato10

1  Yale University School of Medicine, New Haven, CT, USA
2  Johns Hopkins School of Medicine, Baltimore, MD, USA and Johns Hopkins Singapore, Singapore
3  Oregon Health & Science University, Portland, OR, USA
4  University of Miami Miller School of Medicine, Miami, FL, USA
5  Hospital Universitario Fundación Alcorcón, Madrid, Spain
6  OSF Saint Anthony Center for Cancer Care, Rockford, IL, USA
7  Einstein Healthcare Network, Philadelphia, PA, USA
8  Stanford University School of Medicine, Stanford, CA, USA
9  Bristol-Myers Squibb, Wallingford, CT, USA
10  Hospital Británico, UCA School of Medicine, Buenos Aires, Argentina
*Correspondence to: Joseph K Lim, Yale University School of Medicine, 333 Cedar Street, LMP 1080, New Haven, CT 06520 USA. Tel: +1-203-737-6063, Fax: +1-203-785-7273, E-mail: This email address is being protected from spambots. You need JavaScript enabled to view it.

Journal of Clinical and Translational Hepatology 2020;8(4):377-384 DOI: 10.14218/JCTH.2020.00039
Received: May 1, 2020 Accepted: September 5, 2020 Published online: October 10, 2020


Background and Aims: In the REALM (Randomized, Observational 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 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.


Hepatitis B, Antiviral therapy, Clinical outcomes, Event adjudication, Liver cirrhosis

Journal of Clinical and Translational Hepatology 2020 vol. 8, 377-384  [ Html  ] [ PDF Full-text ]

© The Authors 2020. This article is published under the terms of the Creative Commons Attribution-Noncommercial License (CC BY-NC 4.0), which permits use, distribution, and reproduction in any medium, provided the original work is properly cited, the use is non commercial and is otherwise in compliance with the license.


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