Detection bias in open-label trials of anticancer drugs: a meta-epidemiological study

Author:

Funada SatoshiORCID,Luo YanORCID,Kataoka YukiORCID,Yoshioka Takashi,Fujita Yusuke,Yoshida Shinya,Katsura Morihiro,Tada Masafumi,Nishioka Norihiro,Nakamura Yoshiaki,Ueno Kentaro,Uozumi Ryuji,Furukawa Toshi AORCID

Abstract

ObjectivesIn anticancer clinical trials, particularly open-label trials, central reviewers are recommended to evaluate progression-free survival (PFS) and objective response rate (ORR) to avoid detection bias of local investigators. However, it is not clear whether the bias has been adequately identified, or to what extent it consistently distorts the results. Therefore, the objective of this study was to evaluate the detection bias in oncological open-label trials by confirming whether local investigators overestimate the PFS and ORR compared with the findings of central reviewers.DesignMeta-epidemiological study.Data sourcesMEDLINE via PubMed from 1 January 2010 to 30 June 2021.Eligibility criteria for selecting studiesOpen-label, parallel-group superiority, randomised trials of anticancer drugs that adjudicated PFS or ORR by both central reviewers and local investigators.Review methodsWe assessed the values for the same outcome (PFS and ORR) adjudicated by both central reviewers and local investigators. A random-effects model was used to estimate the ratio of HR (RHR) for PFS and the ratio of OR (ROR) for ORR between central reviewers and local investigators. An RHR lower than 1 and an ROR higher than 1 indicated an overestimation of the effect estimated by local investigators.ResultsWe retrieved 1197 records of oncological open-label trials after full-text screening. We identified 171 records (PFS: 149 records, ORR: 136 records) in which both central reviewers and local investigators were used, and included 114 records (PFS: 92 records, ORR: 74 records) for meta-analyses. While the RHR for PFS was 0.95 (95% CI 0.91 to 0.98), the ROR of ORR was 1.00 (95% CI 0.91 to 1.09). The results remained unchanged in the prespecified sensitivity analysis.ConclusionsThis meta-epidemiological study found that overestimation of local investigators has a small impact on evaluating PFS and ORR in oncological open-label trials. However, a limitation of this study is that it did not include data from all trials; hence, the results may not fully evaluate detection bias. The necessity of central reviewers in oncological open-label trials needs to be assessed by further studies that overcome this limitation.Trial registration numberCTR-UMIN000044623.

Funder

Pfizer Health Research Foundation

Kyoto University School of Public Health

Publisher

BMJ

Subject

General Medicine

同舟云学术

1.学者识别学者识别

2.学术分析学术分析

3.人才评估人才评估

"同舟云学术"是以全球学者为主线,采集、加工和组织学术论文而形成的新型学术文献查询和分析系统,可以对全球学者进行文献检索和人才价值评估。用户可以通过关注某些学科领域的顶尖人物而持续追踪该领域的学科进展和研究前沿。经过近期的数据扩容,当前同舟云学术共收录了国内外主流学术期刊6万余种,收集的期刊论文及会议论文总量共计约1.5亿篇,并以每天添加12000余篇中外论文的速度递增。我们也可以为用户提供个性化、定制化的学者数据。欢迎来电咨询!咨询电话:010-8811{复制后删除}0370

www.globalauthorid.com

TOP

Copyright © 2019-2024 北京同舟云网络信息技术有限公司
京公网安备11010802033243号  京ICP备18003416号-3