The European Medicines Agency has in recent years allowed licensing of new pharmaceuticals at an earlier stage in the clinical trial process. When trial evidence is obtained at an early stage, the events of interest, such as disease progression or death, may have only been observed in a small proportion of patients. Health care authorities therefore must decide on the adoption of new technologies based on less mature evidence than previously, resulting in greater uncertainty about clinical- and cost-effectiveness. When a trial is ongoing at the point of decision making, there may be value in continuing the trial in order to collect additional data before making an adoption decision. This can be quantified by the Expected Value of Sample Information (EVSI). However, no guidance exists on how to compute the EVSI for survival data from an ongoing trial, nor on how to account for uncertainty about the choice of survival model in the EVSI calculations. In this article, we describe algorithms for computing the EVSI of extending a trial's follow-up, both where a single known survival model is assumed, and where we are uncertain about the true survival model. We compare a nested Markov Chain Monte Carlo procedure with a non-parametric regression-based method in two synthetic case studies, and find close agreement between the two methods. The regression-based method is fast and straightforward to implement, and scales easily to include any number of candidate survival models in the model uncertainty case. EVSI for ongoing trials can help decision makers determine whether early patient access to a new technology can be justified on the basis of the current evidence or whether more mature evidence is needed.
翻译:欧洲药品管理局近年来允许在临床试验过程的较早阶段发放新药品的许可证,在临床试验过程中允许在临床试验过程的较早阶段继续试验,以便收集更多的病人数据。当在早期阶段获得试验证据时,可能只对少数病人观察到了疾病增加或死亡等令人感兴趣的事件。因此,保健当局必须根据较不成熟的证据决定采用新技术,从而在临床和成本效益方面产生更大的不确定性。当在决策阶段进行试验时,为了在通过决定之前收集更多的病人数据而继续试验可能是有益的。这可以通过抽样信息的预期值加以量化。然而,对于如何在进行中的试验中为生存数据计算EVSI数据而计算EVSI,如疾病增加或死亡等,也许没有指导,对于如何在EVSI计算生存模式的不确定性,如何在EVS计算延长试验的后续行动时,我们描述了计算EVSI的算法,无论是在假定单一已知的生存模式的情况下,还是在我们对真正的生存模式有疑问的地方,我们很容易地找到一个固定的Markov连锁·蒙特卡洛程序与一个非参数性的证据相比较。在两个综合案例研究中,是否采用一个快速的回归分析方法,在快速地确定一个比较,在两个案例的回归分析中,在快速分析中,在两个案例中,是否需要的任何方法是,在进行。在快速分析方法是,在两个综合案例中,在快速分析中,是否需要一个快速地进行。在快速的推算算。