Nikolakopoulos Stavros, Roes Kit C B, van der Lee Johanna H, van der Tweel Ingeborg
Department of Biostatistics, Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Str, 6,131, PO Box 85500, 3508 Utrecht, GA, The Netherlands.
Trials. 2014 Jul 8;15:274. doi: 10.1186/1745-6215-15-274.
At the design stage of a clinical trial, several assumptions have to be made. These usually include guesses about parameters that are not of direct interest but must be accounted for in the analysis of the treatment effect and also in the sample size calculation (nuisance parameters, e.g. the standard deviation or the control group event rate). We conducted a systematic review to investigate the impact of misspecification of nuisance parameters in pediatric randomized controlled trials conducted in intensive care units. We searched MEDLINE through PubMed. We included all publications concerning two-arm RCTs where efficacy assessment was the main objective. We included trials with pharmacological interventions. Only trials with a dichotomous or a continuous outcome were included. This led to the inclusion of 70 articles describing 71 trials. In 49 trial reports a sample size calculation was reported. Relative misspecification could be calculated for 28 trials, 22 with a dichotomous and 6 with a continuous primary outcome. The median [inter-quartile range (IQR)] overestimation was 6.9 [-12.1, 57.8]% for the control group event rate in trials with dichotomous outcomes and -1.5 [-15.3, 5.1]% for the standard deviation in trials with continuous outcomes. Our results show that there is room for improvement in the clear reporting of sample size calculations in pediatric clinical trials conducted in ICUs. Researchers should be aware of the importance of nuisance parameters in study design and in the interpretation of the results.
在临床试验的设计阶段，必须做出若干假设。这些假设通常包括对并非直接关注但在治疗效果分析以及样本量计算中必须考虑的参数的猜测（干扰参数，例如标准差或对照组事件发生率）。我们进行了一项系统评价，以调查重症监护病房中开展的儿科随机对照试验中干扰参数误设的影响。我们通过PubMed检索了MEDLINE。我们纳入了所有以疗效评估为主要目标的双臂随机对照试验的出版物。我们纳入了采用药物干预的试验。仅纳入了具有二分法或连续型结局的试验。这导致纳入了70篇描述71项试验的文章。在49份试验报告中报告了样本量计算情况。对于28项试验可以计算相对误设情况，其中22项试验的主要结局为二分法，6项试验的主要结局为连续型。对于二分法结局试验，对照组事件发生率的中位数[四分位间距（IQR）]高估为6.9 [-12.1, 57.8]%；对于连续型结局试验，标准差的中位数高估为-1.5 [-15.3, 5.1]%。我们的结果表明，在重症监护病房开展的儿科临床试验中，样本量计算的清晰报告仍有改进空间。研究人员应意识到干扰参数在研究设计和结果解释中的重要性。
