Horwitz R I
Am J Med. 1987 Mar;82(3):498-510. doi: 10.1016/0002-9343(87)90450-5.
Randomized clinical trials have become the accepted scientific standard for evaluating therapeutic efficacy. Contradictory results from multiple randomized clinical trials on the same topic have been attributed either to methodologic deficiencies in the design of one of the trials or to small sample sizes that did not provide assurance that a meaningful therapeutic difference would be detected. When 36 topics with conflicting results that included over 200 randomized clinical trials in cardiology and gastroenterology were reviewed, it was discovered that results of randomized clinical trials often disagree because the complexity of the randomized clinical trial design and the clinical setting creates inconsistencies and variation in the therapeutic evaluation. Nine methodologic sources of this variation were identified, including six items concerned with the design of the trials, and three items concerned with interpretation. The design issues include eligibility criteria and the selection of study groups, baseline differences in the available population, variability in indications for the principal and concomitant therapies, protocol requirements of the randomized clinical trial, and management of intermediate outcomes. The issues in interpreting the trials include the regulatory effects of treatments, the frailty of double-blinding, and the occurrence of unexpected trial outcomes. The results of this review suggest that pooled analyses of conflicting results of randomized clinical trials (meta-analyses) may be misleading by obscuring important distinctions among trials, and that enhanced flexibility in strategies for data analysis will be needed to ensure the clinical applicability of randomized clinical trial results.
随机临床试验已成为评估治疗效果公认的科学标准。针对同一主题的多项随机临床试验得出相互矛盾的结果，这要么归因于其中一项试验设计中的方法学缺陷，要么归因于样本量过小，无法确保检测到有意义的治疗差异。在对36个结果相互冲突的主题进行审查时，这些主题涵盖了心脏病学和胃肠病学领域的200多项随机临床试验，发现随机临床试验结果常常不一致，因为随机临床试验设计的复杂性和临床环境在治疗评估中造成了不一致和差异。确定了造成这种差异的九个方法学来源，包括与试验设计相关的六个项目和与解释相关的三个项目。设计问题包括纳入标准和研究组的选择、现有总体人群的基线差异、主要治疗和伴随治疗适应症的变异性、随机临床试验的方案要求以及中间结果的管理。试验解释中的问题包括治疗的调节作用、双盲的脆弱性以及意外试验结果的发生。这项审查结果表明，对随机临床试验相互冲突的结果进行汇总分析（荟萃分析）可能会因掩盖试验之间的重要差异而产生误导，并且需要增强数据分析策略的灵活性，以确保随机临床试验结果的临床适用性。
