Sacks H, Chalmers T C, Smith H
Am J Med. 1982 Feb;72(2):233-40. doi: 10.1016/0002-9343(82)90815-4.
To compare the use of randomized controls (RCTs) and historical controls (HCTs) for clinical trials, we searched the literature for therapies studied by both methods. We found six therapies for which 50 RCTs and 56 HCTs were reported. Forty-four of 56 HCTs (79 percent) found the therapy better than the control regimen, but only 10 of 50 RCTs (20 percent) agreed. For each therapy, the treated patients in RCTs and HCTs of the same therapy was largely due to differences in outcome for the control groups, with HCT control patients generally doing worse than the RCT control groups. Adjustment of the outcomes of the HCTs for prognostic factors, when possible, did not appreciably change the results. The data suggest that biases in patient selection may irretrievably weight the outcome of HCts in favor of new therapies. RCTs may miss clinically important benefits because of inadequate attention to sample size. The predictive value of each might be improved by reconsidering the use of p less than 0.05 as the significance level for all types of clinical trials, and by the use of confidence intervals around estimates of treatment effects.
为比较随机对照试验（RCT）和历史对照试验（HCT）在临床试验中的应用，我们检索了同时采用这两种方法进行研究的疗法的文献。我们发现了六种疗法，针对这些疗法共报告了50项随机对照试验和56项历史对照试验。56项历史对照试验中有44项（79%）发现该疗法优于对照方案，但50项随机对照试验中只有10项（20%）得出相同结论。对于每种疗法，同一疗法的随机对照试验和历史对照试验中接受治疗的患者情况存在差异，这主要归因于对照组的结果不同，历史对照试验中的对照患者通常比随机对照试验中的对照组患者情况更差。在可能的情况下，对历史对照试验的结果进行预后因素调整，并未显著改变结果。数据表明，患者选择方面的偏倚可能会不可挽回地使历史对照试验的结果偏向新疗法。随机对照试验可能因对样本量关注不足而遗漏临床重要益处。通过重新考虑将p值小于0.05作为所有类型临床试验的显著性水平，以及在治疗效果估计周围使用置信区间，可能会提高每种方法的预测价值。
