Stopping or Reporting Early for Positive Results in Randomized Clinical Trials: The National Cancer Institute Cooperative Group Experience From 1990 to 2005
Stopping or Reporting Early for Positive Results in Randomized Clinical Trials: The National Cancer Institute Cooperative Group Experience From 1990 to 2005
复制标题
DOI：
10.1200/jco.2008.19.5339
复制
发表时间：
2009-04-01
影响因子：
45.3
通讯作者：
Mooney, Margaret
中科院分区：
文献类型：
--
作者：
Korn, Edward L.;Freidlin, Boris;Mooney, Margaret
随机临床试验的设计有停止边界，以指导数据监测委员会做出有关正在进行的试验的决策。特别是，当看到非常积极的结果并且跨越界限时，数据监测委员会可能会建议比方案中规定的最终分析时间更早地向公众发布结果。对于仍在累积的试验，这也意味着停止累积。由于早期分析中有关治疗效果的信息比最终分析中的信息更为有限，因此有人提出了在试验设计中将早期停止以获得阳性结果是否适当的问题。特别是，人们担心早期看到的治疗效果可能并不真实，或者可能过于乐观。为了研究这个问题，我们收集了有关国家癌症研究所合作组试验的治疗效果的信息，这些试验因阳性结果而提前停止（试验停止/发布时和进一步随访时的信息）。找到了二十七个这样的试验。在这些具有足够随访信息的 18 项试验中，有 17 项在最后一次随访时的治疗效果与停止/释放时相似或仅稍小一些。我们批判性地评估人们可能担心提前停止以获得积极结果的原因。我们的结论是，对于设计良好的中期监测计划的试验来说，尽早停止以获得积极结果的能力是试验设计的重要组成部分，使公众尽快从研究结论中受益。 J 临床肿瘤杂志 27：1712-1721。由美国临床肿瘤学会出版
Randomized clinical trials are designed with stopping boundaries to guide data monitoring committees with their decision making concerning ongoing trials. In particular, when extremely positive results are seen and a boundary is crossed, the data monitoring committee may recommend releasing the results earlier to the public than at the definitive final analysis time specified in the protocol. For trials that are still accruing, this also means stopping accrual. Because the information about treatment efficacy is more limited in an early analysis than in a final analysis, questions have been raised about the appropriateness of incorporating early stopping for positive results in trial designs. In particular, there are concerns that treatment effects seen early may not be real or may be overly optimistic. To examine this issue, we collected information about treatment efficacy on National Cancer Institute Cooperative Group trials that were stopped early for positive results (information both at the time the trial was stopped/released and at times of further follow-up). Twenty-seven such trials were located. For 17 of 18 of these trials with sufficient follow-up information, the treatment effect was similar or only slightly smaller at last follow-up compared with the stopping/release time. We critically evaluate reasons why one might be concerned about early stopping for positive results. We conclude that for trials with well-designed interim monitoring plans, the ability to stop early for positive results is an important component of the trial design, allowing the public to benefit as soon as possible from the study conclusions. J Clin Oncol 27:1712-1721. Published by the American Society of Clinical Oncology