网络荟萃分析预测已批准治疗在新适应症中的疗效。

IF 5 2区 生物学 Q1 MATHEMATICAL & COMPUTATIONAL BIOLOGY Research Synthesis Methods Pub Date : 2023-12-03 DOI:10.1002/jrsm.1683
Jennifer L. Proper, Haitao Chu, Purvi Prajapati, Michael D. Sonksen, Thomas A. Murray
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引用次数: 0

摘要

药物再利用是指为现有药物发现新的治疗用途的过程。与传统的药物发现相比,药物再利用因其速度、成本和降低失败风险而具有吸引力。然而,现有的药物再利用方法涉及复杂的、计算密集型的分析方法,这些方法在实践中并未广泛使用。相反,重新确定用途的决定往往是基于有限的经验证据的主观判断。在本文中,我们开发了一个新的贝叶斯网络荟萃分析(NMA)框架,可以预测已批准的治疗在新适应症中的疗效,从而确定候选治疗的再利用。我们通过两个主要步骤获得预测:首先,我们使用标准的NMA模型来估计由两个适应症研究的治疗组成的网络的平均相对效果,以及只研究一个适应症的一种治疗。然后,我们使用不同的策略来建模相对效应之间的相关性,这些策略在不同适应症和同一药物类别中如何建模治疗。我们使用模拟研究评估了每个模型的预测性能,并发现最小化候选治疗的后中位数均方根误差的模型取决于可用数据的数量、适应症之间的相关性水平以及治疗效果是否因药物类别而异。我们通过讨论银屑病和银屑病关节炎的一个说明性例子来总结,并发现候选治疗在未来的试验中有很高的成功概率。
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Network meta analysis to predict the efficacy of an approved treatment in a new indication

Drug repurposing refers to the process of discovering new therapeutic uses for existing medicines. Compared to traditional drug discovery, drug repurposing is attractive for its speed, cost, and reduced risk of failure. However, existing approaches for drug repurposing involve complex, computationally-intensive analytical methods that are not widely used in practice. Instead, repurposing decisions are often based on subjective judgments from limited empirical evidence. In this article, we develop a novel Bayesian network meta-analysis (NMA) framework that can predict the efficacy of an approved treatment in a new indication and thereby identify candidate treatments for repurposing. We obtain predictions using two main steps: first, we use standard NMA modeling to estimate average relative effects from a network comprised of treatments studied in both indications in addition to one treatment studied in only one indication. Then, we model the correlation between relative effects using various strategies that differ in how they model treatments across indications and within the same drug class. We evaluate the predictive performance of each model using a simulation study and find that the model minimizing root mean squared error of the posterior median for the candidate treatment depends on the amount of available data, the level of correlation between indications, and whether treatment effects differ, on average, by drug class. We conclude by discussing an illustrative example in psoriasis and psoriatic arthritis and find that the candidate treatment has a high probability of success in a future trial.

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来源期刊
Research Synthesis Methods
Research Synthesis Methods MATHEMATICAL & COMPUTATIONAL BIOLOGYMULTID-MULTIDISCIPLINARY SCIENCES
CiteScore
16.90
自引率
3.10%
发文量
75
期刊介绍: Research Synthesis Methods is a reputable, peer-reviewed journal that focuses on the development and dissemination of methods for conducting systematic research synthesis. Our aim is to advance the knowledge and application of research synthesis methods across various disciplines. Our journal provides a platform for the exchange of ideas and knowledge related to designing, conducting, analyzing, interpreting, reporting, and applying research synthesis. While research synthesis is commonly practiced in the health and social sciences, our journal also welcomes contributions from other fields to enrich the methodologies employed in research synthesis across scientific disciplines. By bridging different disciplines, we aim to foster collaboration and cross-fertilization of ideas, ultimately enhancing the quality and effectiveness of research synthesis methods. Whether you are a researcher, practitioner, or stakeholder involved in research synthesis, our journal strives to offer valuable insights and practical guidance for your work.
期刊最新文献
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