Analysis of drug combinations: current methodological landscape.
Analysis of drug combinations: current methodological landscape.
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DOI：
10.1002/prp2.149
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发表时间：
2015-06
影响因子：
2.6
通讯作者：
Guedj, Mickael
中科院分区：
文献类型：
--
作者：
Foucquier, Julie;Guedj, Mickael
联合疗法利用了更好的疗效、更低的毒性和减少耐药性发展的机会，由于这些优点，已成为治疗几种疾病的标准，并在未得到满足的医疗需求的适应症中继续代表着一种有前途的方法。在这种背景下，研究联合用药的效果，以便提供证据表明与单一药物相比具有显著的优势，这是特别有意义的。在这一领域的研究已经产生了大量的论文，并揭示了几个问题。在这里，我们提出了关于联合效应研究的当前方法学图景的概述。首先，我们的目标是提供理解最常用方法所需的最小数学和药理学概念集，分为基于效果的方法和基于剂量-效果的方法，并根据各自的实际优势和局限性进行介绍。然后，我们讨论了科学家在开发新的联合疗法的每一步都必须面对的六个主要常见的方法学问题。特别是，在缺乏适用于所有生物医学情况的参考方法学的情况下，药物组合的分析应该受益于集中、适当和严格地应用这里所回顾的概念和方法。
Combination therapies exploit the chances for better efficacy, decreased toxicity, and reduced development of drug resistance and owing to these advantages, have become a standard for the treatment of several diseases and continue to represent a promising approach in indications of unmet medical need. In this context, studying the effects of a combination of drugs in order to provide evidence of a significant superiority compared to the single agents is of particular interest. Research in this field has resulted in a large number of papers and revealed several issues. Here, we propose an overview of the current methodological landscape concerning the study of combination effects. First, we aim to provide the minimal set of mathematical and pharmacological concepts necessary to understand the most commonly used approaches, divided into effect-based approaches and dose–effect-based approaches, and introduced in light of their respective practical advantages and limitations. Then, we discuss six main common methodological issues that scientists have to face at each step of the development of new combination therapies. In particular, in the absence of a reference methodology suitable for all biomedical situations, the analysis of drug combinations should benefit from a collective, appropriate, and rigorous application of the concepts and methods reviewed here.