Department of Public Health, Erasmus MC, P,O, Box 2040, 3000 CA Rotterdam, the Netherlands.
Trials. 2011 Aug 25;12:201. doi: 10.1186/1745-6215-12-201.
In Traumatic Brain Injury (TBI), large between-centre differences in outcome exist and many clinicians believe that such differences influence estimation of the treatment effect in randomized controlled trial (RCTs). The aim of this study was to assess the influence of between-centre differences in outcome on the estimated treatment effect in a large RCT in TBI.
We used data from the MRC CRASH trial on the efficacy of corticosteroid infusion in patients with TBI. We analyzed the effect of the treatment on 14 day mortality with fixed effect logistic regression. Next we used random effects logistic regression with a random intercept to estimate the treatment effect taking into account between-centre differences in outcome. Between-centre differences in outcome were expressed with a 95% range of odds ratios (OR) for centres compared to the average, based on the variance of the random effects (tau2). A random effects logistic regression model with random slopes was used to allow the treatment effect to vary by centre. The variation in treatment effect between the centres was expressed in a 95% range of the estimated treatment ORs.
In 9978 patients from 237 centres, 14-day mortality was 19.5%. Mortality was higher in the treatment group (OR = 1.22, p = 0.00010). Using a random effects model showed large between-centre differences in outcome (95% range of centre effects: 0.27- 3.71), but did not substantially change the estimated treatment effect (OR = 1.24, p = 0.00003). There was limited, although statistically significant, between-centre variation in the treatment effect (OR = 1.22, 95% treatment OR range: 1.17-1.26).
Large between-centre differences in outcome do not necessarily affect the estimated treatment effect in RCTs, in contrast to current beliefs in the clinical area of TBI.
在创伤性脑损伤（TBI）中，中心之间的结果存在很大差异，许多临床医生认为这种差异会影响随机对照试验（RCT）中治疗效果的估计。本研究旨在评估 TBI 中一项大型 RCT 中结果的中心间差异对估计治疗效果的影响。
我们使用 MRC CRASH 试验中关于皮质类固醇输注治疗 TBI 患者疗效的数据。我们使用固定效应逻辑回归分析治疗对 14 天死亡率的影响。接下来，我们使用具有随机截距的随机效应逻辑回归来估计考虑到结果的中心间差异的治疗效果。基于随机效应的方差（tau2），使用 95%的比值比（OR）范围来表示中心之间的结果差异，该范围用于与平均值相比的中心。使用具有随机斜率的随机效应逻辑回归模型来允许治疗效果因中心而异。中心之间治疗效果的差异以估计治疗 OR 的 95%范围表示。
在 237 个中心的 9978 名患者中，14 天死亡率为 19.5%。治疗组死亡率较高（OR=1.22，p=0.00010）。使用随机效应模型显示出结果的中心间存在很大差异（中心效应的 95%范围：0.27-3.71），但并未实质上改变估计的治疗效果（OR=1.24，p=0.00003）。虽然存在统计学意义，但治疗效果的中心间差异有限（OR=1.22，95%治疗 OR 范围：1.17-1.26）。
与 TBI 临床领域的当前观念相反，中心间结果的很大差异不一定会影响 RCT 中估计的治疗效果。
