Moroz Veronica, Wilson Jayne S, Kearns Pamela, Wheatley Keith
Cancer Research UK Clinical Trials Unit, School of Cancer Sciences, University of Birmingham, Vincent Drive, Edgbaston, Birmingham B15 2TT, UK.
Trials. 2014 Dec 10;15:481. doi: 10.1186/1745-6215-15-481.
Historically controlled studies are commonly undertaken in paediatric oncology, despite their potential biases. Our aim was to compare the outcome of the control group in randomised controlled trials (RCTs) in paediatric oncology with those anticipated in the sample size calculations in the protocols. Our rationale was that, had these RCTs been performed as historical control studies instead, the available outcome data used to calculate the sample size in the RCT would have been used as the historical control outcome data.
A systematic search was undertaken for published paediatric oncology RCTs using the Cochrane Central Register of Controlled Trials (CENTRAL) database from its inception up to July 2013. Data on sample size assumptions and observed outcomes (timetoevent and proportions) were extracted to calculate differences between randomised and historical control outcomes, and a one-sample t-test was employed to assess whether the difference between anticipated and observed control groups differed from zero.
Forty-eight randomised questions were included. The median year of publication was 2005, and the range was from 1976 to 2010. There were 31 superiority and 11 equivalence/noninferiority randomised questions with time-to-event outcomes. The median absolute difference between observed and anticipated control outcomes was 5.0% (range: -23 to +34), and the mean difference was 3.8% (95% CI: +0.57 to +7.0; P = 0.022).
Because the observed control group (that is, standard treatment arm) in RCTs performed better than anticipated, we found that historically controlled studies that used similar assumptions for the standard treatment were likely to overestimate the benefit of new treatments, potentially leading to children with cancer being given ineffective therapy that may have additional toxicity.
尽管存在潜在偏倚，但历史对照研究在儿科肿瘤学中仍普遍开展。我们的目的是比较儿科肿瘤学随机对照试验（RCT）中对照组的结果与方案中样本量计算所预期的结果。我们的理由是，如果这些RCT改为作为历史对照研究进行，那么用于RCT中计算样本量的现有结果数据就会被用作历史对照结果数据。
使用Cochrane对照试验中心注册库（CENTRAL）数据库，对从其建立到2013年7月发表的儿科肿瘤学RCT进行系统检索。提取样本量假设和观察到的结果（事件发生时间和比例）的数据，以计算随机对照结果与历史对照结果之间的差异，并采用单样本t检验评估预期对照组与观察到的对照组之间的差异是否不同于零。
纳入了48个随机问题。发表年份的中位数为2005年，范围是1976年至2010年。有31个优效性和11个等效性/非劣效性随机问题涉及事件发生时间结果。观察到的对照组结果与预期对照组结果的中位数绝对差异为5.0%（范围：-23%至+34%），平均差异为3.8%（95%CI：+0.57%至+7.0%；P = 0.022）。
由于RCT中观察到的对照组（即标准治疗组）表现优于预期，我们发现使用类似标准治疗假设的历史对照研究可能高估了新治疗的益处，这可能导致癌症患儿接受无效治疗，而这种治疗可能还具有额外的毒性。
