Simes R J
Stat Med. 1987 Jan-Feb;6(1):11-29. doi: 10.1002/sim.4780060104.
In evaluating therapies, clinical investigators often need to rely on the published clinical trial literature which may be biased in favour of studies with positive or 'encouraging' results and this may lead to erroneous conclusions of therapeutic effectiveness. The problem of publication bias can be magnified when the evaluation is based on a pooled analysis of clinical trial results, since in this case even small differences between treatment groups may reach statistical significance. In this paper a model is developed for pooling the results of clinical trials which is free from publication bias. It is proposed that an international registry of all clinical trials be established with the objectives and endpoints of each trial clearly defined in the register. In this way for each therapeutic issue researchers can select a cohort of clinical trials independently from the trial results. The approach is illustrated using the International Cancer Research Data Bank (ICRDB) registry of cancer clinical trials to evaluate the effect of chemotherapy on survival in advanced ovarian cancer. In this example, the conclusions based on a pooled analysis of registered trials have important differences from a more traditional review of the published trials. Implications of the results and problems in implementing the model are discussed.
在评估治疗方法时，临床研究人员常常需要依赖已发表的临床试验文献，而这些文献可能偏向于那些有阳性或“鼓舞人心”结果的研究，这可能导致对治疗效果得出错误结论。当评估基于对临床试验结果的汇总分析时，发表偏倚问题可能会被放大，因为在这种情况下，即使治疗组之间的微小差异也可能达到统计学显著性。本文开发了一种用于汇总临床试验结果的模型，该模型不存在发表偏倚。建议建立一个所有临床试验的国际登记处，在登记处中明确界定每个试验的目标和终点。通过这种方式，对于每个治疗问题，研究人员可以独立于试验结果选择一组临床试验。使用国际癌症研究数据库（ICRDB）的癌症临床试验登记处来评估化疗对晚期卵巢癌生存率的影响，对该方法进行了说明。在这个例子中，基于对登记试验的汇总分析得出的结论与对已发表试验进行的更传统综述有重要差异。讨论了结果的影响以及实施该模型存在的问题。
