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数据监查委员会——预见意外
Data Monitoring Committees — Expect the Unexpected


David L. DeMets ... 心脑血管疾病 • 2016.10.06

自1967年格林伯格报告(Greenberg Report)的建议完成(在晚些时候发表1)至今已有50年,独立专家组已监查了许多临床试验的进展,内容包括获益的早期明确证据、危害的确凿证据或因无潜在获益而致使继续试验徒劳无益的充分证据。设立此类监查主要由伦理责任所激发;对于旨在预防或延迟严重结局的治疗试验,一旦证据明确,人们就会希望停止试验,并将更优效的治疗用于临床。在整个试验过程中,评估风险和获益需要人们频繁查看逐渐累积的疗效和安全性数据。为使研究者和赞助方无偏倚地管理试验,以及为确保对逐渐累积数据的客观评估,研究中会设立被称为数据监查委员会(data monitor­ing committee,DMC)、数据和安全性监查委员会(data and safety monitoring boards)或其他称呼2的独立委员会,以履行该监查职责,并向研究者和赞助方提出包括提前终止在内的试验修改建议。这些委员会需要有多学科的专业知识和经验,其中包括中期数据监查所需的统计学方法的知识;他们还关注招募进程,以及试验在方案依从性、数据收集和随访完整性等方面的总体质量。

数据一般由DMC依照随机分配的干预组审查;在打印版报告中应该完全标示这些干预组,也可被标记为“A组和B组”,DMC知晓报告中A组和B组的特征2-4。数据审查后,DMC向试验指导委员会提出试验依照计划继续或由于上面提到的原因提前终止的建议(DMC职责总结见表1)。冠心病药物方案(Coronary Drug Project)是由当时被称为美国国家心脏研究所(National Heart Institute)的机构赞助的一项大型早期心血管试验,很可能是第一项纳入独立专家进行中期审查的试验5,提供了许多关于DMC程序的经验与教训6,7。此程序进一步发展,加上美国国立卫生研究院(National Institutes of Health,NIH)模式的一些改良11,于20世纪70年代成为美国联邦政府赞助的大部分随机试验采用的基本方法2,8,9,并最终成为越来越多由工业界赞助的三期试验的一般方法10。随着临床试验实施本身在管理和科学性方面的发展,DMC也继续发展。

尽管在大部分情况下,试验依照计划完成,DMC未提出提前终止或重大修改建议,但是有些试验已向DMC提出了具有挑战性的问题12-19。我们在本文中简要总结了提前终止试验的几个经典案例,随后讨论一些近期案例,以进一步阐明DMC职责的复杂性。





作者信息

David L. DeMets, Ph.D., and Susan S. Ellenberg, Ph.D.
From the Department of Biostatistics and Medical Informatics, University of Wisconsin–Madison, Madison (D.L.D.); and the Department of Biostatistics and Epidemiology, University of Pennsylvania Perelman School of Medicine, Philadelphia (S.S.E.). Address reprint requests to Dr. DeMets at the Department of Biostatistics and Medical Informatics, University of Wisconsin–Madison School of Medicine and Public Health, 610 Walnut St., Rm. 201 WARF, Madison, WI 53726, or at demets@biostat.wisc.edu.

 

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