Gallo Paul, Mao Lu, Shih Vivian H
a Novartis Pharmaceuticals , East Hanover , New Jersey , USA.
J Biopharm Stat. 2014;24(5):976-93. doi: 10.1080/10543406.2014.932285.
A feature increasingly utilized in clinical trial practice is to allow a study to stop early when it seems unlikely to achieve its primary efficacy objectives. This is commonly referred to as stopping for futility, and can be motivated by ethical and financial considerations. A number of methods for addressing futility have been described in the literature, including rules based upon conditional power, predictive probability, beta spending functions, and others. We consider futility stopping from the point of view of quantifying and providing an objective sensible balance between risks of incorrect decisions (e.g., stopping trials which should continue, and continuing trials which should stop), and discuss how specific considerations within a trial can lead to choice of a sensible scheme. This approach is not specific to any particular scales in the literature such as those just mentioned, and we describe interrelationships among criteria expressed on different scales. As futility may be evaluated multiple times in a long-term trial and the amount of information available at scheduled interim analyses may be difficult to predict in advance, we present a specific optimality criterion and discuss which of the familiar scales tend to produce schemes simple to describe and implement, and with better behavior across different timepoints at which futility might be evaluated.
在临床试验实践中越来越多地采用的一个特点是，当一项研究似乎不太可能实现其主要疗效目标时，允许该研究提前终止。这通常被称为因无效而终止，其动机可能是伦理和财务方面的考虑。文献中已经描述了许多处理无效性的方法，包括基于条件功效、预测概率、β花费函数等的规则。我们从量化以及在错误决策风险（例如，终止本应继续的试验，以及继续本应终止的试验）之间提供客观合理平衡的角度来考虑无效性终止，并讨论试验中的具体考虑因素如何导致选择合理的方案。这种方法并不特定于文献中提到的任何特定尺度，我们描述了不同尺度上表达的标准之间的相互关系。由于在长期试验中可能会多次评估无效性，并且在预定的中期分析时可用的信息量可能难以预先预测，我们提出了一个特定的最优性标准，并讨论了哪些常见尺度倾向于产生易于描述和实施的方案，以及在可能评估无效性的不同时间点具有更好的表现。
