Blinded independent central review of progression-free survival in phase III clinical trials: Important design element or unnecessary expense?
Blinded independent central review of progression-free survival in phase III clinical trials: Important design element or unnecessary expense?
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DOI：
10.1200/jco.2008.16.1711
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发表时间：
2008-08-01
影响因子：
45.3
通讯作者：
Mooney, Margaret M.
中科院分区：
文献类型：
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作者：
Dodd, Lori E.;Korn, Edward L.;Mooney, Margaret M.
无进展生存是晚期疾病环境下的重要终点。在随机临床试验中，对进展的盲目独立中心审查(BICR)被提倡用来控制可能由进展评估中的错误引起的偏差。然而，尽管BICR减少了一些潜在的偏差，但它并没有消除治疗效果评估中的所有偏差。事实上，正如通常进行的那样，BICR可能会因为信息性审查而引入偏见，这是因为必须审查未经证实的地方确定的进展。在这篇文章中，我们讨论了BICR的基本原理和实施独立审查的不同方式。我们讨论了这些方法的局限性，并回顾了报告实施BICR的已发表试验。我们使用随机第二阶段试验的数据证明了信息性审查的存在。我们的结论是，一致应用测量标准的双盲试验是确保试验结果无偏见的最佳手段。当这样的设计不实用时，不推荐将BICR作为减少偏差的一般策略。然而，BICR可能是一种有用的审计工具，可以用来评估略微积极的结果的可靠性。
Progression-free survival is an important end point in advanced disease settings. Blinded independent central review (BICR) of progression in randomized clinical trials has been advocated to control bias that might result from errors in progression assessments. However, although BICR lessens some potential biases, it does not remove all biases from evaluations of treatment effectiveness. In fact, as typically conducted, BICRs may introduce bias because of informative censoring, which results from having to censor unconfirmed locally determined progressions. In this article, we discuss the rationale for BICR and different ways of implementing independent review. We discuss the limitations of these approaches and review published trials that report implementing BICR. We demonstrate the existence of informative censoring using data from a randomized phase II trial. We conclude that double-blinded trials with consistent application of measurement criteria are the best means of ensuring unbiased trial results. When such designs are not practical, BICR is not recommended as a general strategy for reducing bias. However, BICR may be useful as an auditing tool to assess the reliability of marginally positive results.