University of Glasgow, Glasgow, UK.
Contemp Clin Trials. 2011 Nov;32(6):893-901. doi: 10.1016/j.cct.2011.07.007. Epub 2011 Jul 18.
Randomised controlled trials (RCTs) which involve cost-effectiveness evaluations rarely use health economic input when undertaking sample size calculations for the trial design; however, in studies undertaken with cost-effectiveness as the primary outcome, sample size calculations should be directly related to the cost-effectiveness result rather than to the effectiveness outcome alone. This paper reports on a case in which a clinical trial design sample size and power calculations were determined with regard to cost-effectiveness using the net monetary benefit (NMB) approach to demonstrate the feasibility of sample size calculation for cost-effectiveness in a real life setting. The proposed RCT of fetal fibronectin screening (fFN) for women with threatened pre-term labour is discussed, followed by the design of a preliminary model to inform the trial design calculation. The predictions from this pre-trial indicate potential cost-savings, but with a marginal detrimental impact on the effectiveness endpoint, neonatal morbidity. The NMB approach for cost-effectiveness is discussed and used to calculate the required sample sizes for different powers. The sample size calculations are then recalculated using a non-inferiority margin, to ensure that the NMB sample size for the trial was also sufficient to demonstrate non-inferiority for the effectiveness endpoint. Finally, a probabilistic analysis explored uncertainty in the model parameters and the impact on sample size. Considerations of economic assessments alongside clinical trials can and should be used to guide conventional trial design. This paper demonstrates the feasibility of such calculations, whilst simultaneously highlighting limitations and demonstrating the role for economic considerations to guide non-inferiority margins.
随机对照试验（RCTs）在进行试验设计的样本量计算时，很少涉及成本效益评估；然而，在以成本效益为主要结果的研究中，样本量计算应直接与成本效益结果相关，而不仅仅与效果结果相关。本文报告了一个案例，即使用净货币效益（NMB）方法在考虑成本效益的情况下确定临床试验设计的样本量和功效计算，以证明在实际环境中进行成本效益的样本量计算的可行性。讨论了针对有早产威胁的孕妇进行胎儿纤维连接蛋白筛查（fFN）的 RCT，并设计了一个初步模型来为试验设计计算提供信息。该预试验的预测表明存在潜在的成本节约，但对新生儿发病率等有效性终点有轻微的不利影响。讨论了成本效益的 NMB 方法，并用于计算不同功效的所需样本量。然后使用非劣效性边界重新计算样本量计算，以确保试验的 NMB 样本量也足以证明有效性终点的非劣效性。最后，概率分析探讨了模型参数的不确定性及其对样本量的影响。经济评估与临床试验一起考虑可以而且应该用于指导常规试验设计。本文证明了这种计算的可行性，同时强调了局限性，并展示了经济考虑因素在指导非劣效性边界方面的作用。
