Faye D Baldwin, Rukun K S Khalaf, Ruwanthi Kolamunnage-Dona, Andrea L Jorgensen
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引用次数: 0
Abstract
Background: Target trial emulation involves the application of design principles from randomised controlled trials (RCTs) to observational data, and is particularly useful in situations where an RCT would be unfeasible. Biomarker-guided trials, which incorporate biomarkers within their design to either guide treatment and/or determine eligibility, are often unfeasible in practice due to sample size requirements or ethical concerns. Here, we undertake a systematic review of methodologies used in target trial emulations, comparing treatment effectiveness, critically appraising them, and considering their applicability to the emulation of biomarker-guided trials. Methods: A comprehensive search strategy was developed to identify studies reporting on methods for target trial emulation comparing the effectiveness of treatments using observational data, and applied to the following bibliographic databases: PubMed, Scopus, Web of Science, and Ovid MEDLINE. A narrative description of methods identified in the review was undertaken alongside a critique of their relative strengths and limitations. Results: We identified a total of 59 papers: 47 emulating a target trial ('application' studies), and 12 detailing methods to emulate a target trial ('methods' studies). A total of 25 papers were identified as emulating a biomarker-guided trial (42%). While all papers reported methods to adjust for baseline confounding, 40% of application papers did not specify methods to adjust for time-varying confounding. Conclusions: This systematic review has identified a range of methods used to control for baseline, time-varying, and residual/unmeasured confounding within target trial emulation and provides a guide for researchers interested in emulation of biomarker-guided trials.
背景:目标试验模拟涉及将随机对照试验(RCT)的设计原则应用于观察数据,在RCT不可行的情况下特别有用。生物标志物引导试验,将生物标志物纳入其设计中以指导治疗和/或确定资格,由于样本量要求或伦理问题,在实践中往往是不可行的。在这里,我们对目标试验模拟中使用的方法进行了系统的回顾,比较了治疗效果,批判性地评估了它们,并考虑了它们在生物标志物引导试验模拟中的适用性。方法:采用一种综合检索策略来识别使用观察数据进行目标试验模拟方法比较治疗有效性的研究,并应用于以下书目数据库:PubMed、Scopus、Web of Science和Ovid MEDLINE。对审查中确定的方法进行了叙述性描述,并对其相对优势和局限性进行了批评。结果:我们共确定了59篇论文:47篇模拟目标试验(“应用”研究),12篇详细描述模拟目标试验的方法(“方法”研究)。共有25篇论文被确定为模拟生物标志物引导的试验(42%)。虽然所有的论文都报告了调整基线混杂的方法,但40%的应用论文没有指定调整时变混杂的方法。结论:本系统综述确定了目标试验模拟中用于控制基线、时变和残留/未测量混杂的一系列方法,并为对生物标志物引导试验模拟感兴趣的研究人员提供了指导。
期刊介绍:
Journal of Personalized Medicine (JPM; ISSN 2075-4426) is an international, open access journal aimed at bringing all aspects of personalized medicine to one platform. JPM publishes cutting edge, innovative preclinical and translational scientific research and technologies related to personalized medicine (e.g., pharmacogenomics/proteomics, systems biology). JPM recognizes that personalized medicine—the assessment of genetic, environmental and host factors that cause variability of individuals—is a challenging, transdisciplinary topic that requires discussions from a range of experts. For a comprehensive perspective of personalized medicine, JPM aims to integrate expertise from the molecular and translational sciences, therapeutics and diagnostics, as well as discussions of regulatory, social, ethical and policy aspects. We provide a forum to bring together academic and clinical researchers, biotechnology, diagnostic and pharmaceutical companies, health professionals, regulatory and ethical experts, and government and regulatory authorities.