将 Estimand 框架应用于非劣效性试验。

IF 1.3 4区 医学 Q4 PHARMACOLOGY & PHARMACY Pharmaceutical Statistics Pub Date : 2024-08-08 DOI:10.1002/pst.2433
Helle Lynggaard, Oliver N Keene, Tobias Mütze, Sunita Rehal
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引用次数: 0

摘要

大多数已发表的估算值框架应用都集中在优效试验上。然而,与优效试验相比,非劣效试验面临着特殊的挑战。国际人用药品技术要求协调委员会在其关于临床试验中的估计指标和敏感性分析的增编中指出,在以非劣效性为目标的临床试验中实施估计指标时可能会有一些特殊的考虑因素,但几乎没有提供任何指导。本文讨论了试验团队在为具有非劣效性目标的临床试验定义估计指标时应注意的事项。我们讨论了估算指标框架如何采用增补前方式确定非劣效性,包括讨论每项协议分析集的作用。我们研究了在非劣效性试验中可以提出哪些临床问题,并概述了为什么我们认为将估计值描述为 "保守 "是不明智的。我们还讨论了估计指标框架对非劣效性试验中主要考虑因素的影响,如试验是否应该有一个以上的主要估计指标、非劣效边际的选择、检测灵敏度、从非劣效到优效的转换以及估计。最后,我们提供了一份建议清单,以及在以非劣效性为目标的试验中定义估计指标的重要注意事项。
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Applying the Estimand Framework to Non‐Inferiority Trials.

Most published applications of the estimand framework have focused on superiority trials. However, non-inferiority trials present specific challenges compared to superiority trials. The International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use notes in their addendum on estimands and sensitivity analysis in clinical trials that there may be special considerations to the implementation of estimands in clinical trials with a non-inferiority objective yet provides little guidance. This paper discusses considerations that trial teams should make when defining estimands for a clinical trial with a non-inferiority objective. We discuss how the pre-addendum way of establishing non-inferiority can be embraced by the estimand framework including a discussion of the role of the Per Protocol analysis set. We examine what clinical questions of interest can be formulated in the context of non-inferiority trials and outline why we do not think it is sensible to describe an estimand as 'conservative'. The impact of the estimand framework on key considerations in non-inferiority trials such as whether trials should have more than one primary estimand, the choice of non-inferiority margin, assay sensitivity, switching from non-inferiority to superiority and estimation are discussed. We conclude by providing a list of recommendations, and important considerations for defining estimands for trials with a non-inferiority objective.

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来源期刊
Pharmaceutical Statistics
Pharmaceutical Statistics 医学-统计学与概率论
CiteScore
2.70
自引率
6.70%
发文量
90
审稿时长
6-12 weeks
期刊介绍: Pharmaceutical Statistics is an industry-led initiative, tackling real problems in statistical applications. The Journal publishes papers that share experiences in the practical application of statistics within the pharmaceutical industry. It covers all aspects of pharmaceutical statistical applications from discovery, through pre-clinical development, clinical development, post-marketing surveillance, consumer health, production, epidemiology, and health economics. The Journal is both international and multidisciplinary. It includes high quality practical papers, case studies and review papers.
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