Synergy detection: A practical guide to statistical assessment of potential drug combinations.

IF 1.3 4区 医学 Q4 PHARMACOLOGY & PHARMACY Pharmaceutical Statistics Pub Date : 2024-04-02 DOI:10.1002/pst.2383
Elli Makariadou, Xuechen Wang, Nicholas Hein, Negera W Deresa, Kathy Mutambanengwe, Bie Verbist, Olivier Thas
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Abstract

Combination treatments have been of increasing importance in drug development across therapeutic areas to improve treatment response, minimize the development of resistance, and/or minimize adverse events. Pre-clinical in-vitro combination experiments aim to explore the potential of such drug combinations during drug discovery by comparing the observed effect of the combination with the expected treatment effect under the assumption of no interaction (i.e., null model). This tutorial will address important design aspects of such experiments to allow proper statistical evaluation. Additionally, it will highlight the Biochemically Intuitive Generalized Loewe methodology (BIGL R package available on CRAN) to statistically detect deviations from the expectation under different null models. A clear advantage of the methodology is the quantification of the effect sizes, together with confidence interval while controlling the directional false coverage rate. Finally, a case study will showcase the workflow in analyzing combination experiments.

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协同作用检测:潜在药物组合统计评估实用指南》。
在各治疗领域的药物研发中,联合疗法的重要性与日俱增,它可以改善治疗反应,最大限度地减少耐药性的产生,和/或最大限度地减少不良反应。临床前体外联合实验旨在通过比较联合治疗的观察效果和无相互作用假设(即无效模型)下的预期治疗效果,在药物研发过程中探索此类药物联合治疗的潜力。本教程将讨论此类实验的重要设计方面,以便进行适当的统计评估。此外,它还将重点介绍生化直观广义卢韦法(BIGL R 软件包,可在 CRAN 上下载),用于统计检测不同无效模型下的预期偏差。该方法的一个明显优势是可以量化效应大小和置信区间,同时控制方向性错误覆盖率。最后,一个案例研究将展示分析组合实验的工作流程。
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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.
期刊最新文献
Bayesian Solutions for Assessing Differential Effects in Biomarker Positive and Negative Subgroups. Pre-Posterior Distributions in Drug Development and Their Properties. Beyond the Fragility Index. A Model-Based Trial Design With a Randomization Scheme Considering Pharmacokinetics Exposure for Dose Optimization in Oncology. Potential Bias Models With Bayesian Shrinkage Priors for Dynamic Borrowing of Multiple Historical Control Data.
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