Randomized controlled trials (RCTs) are considered the gold standard for estimating the effectiveness of a treatment. However, in many instances they are impractical to conduct because of time limitations, cost restrictions, or ethical reasons. As a consequence, non-randomized observational studies have an important role in comparative effectiveness and safety research since they can address issues that would not be possible using conventional RCT methodology. Observational studies can be strategically designed to reduce the risk of potential sources of bias by emulating the design principles of an equivalent but ideal randomized trial - the target trial - that would answer the research question of interest. In this article, we review some of the necessary components of observational studies required for valid causal inference within the framework of target trial emulation, so as to avoid common methodological pitfalls of study design. We discuss the assumptions of consistency, time-zero specification, exchangeability and positivity. To illustrate these concepts in a context where existing knowledge is well-established through clinical trials, we evaluate and compare the treatment effects of vitamin K antagonists (VKA) against no VKA (No VKA) on the treatment of atrial fibrillation from two real-world observational studies, namely the GARFIELD-AF and ORBIT-AF registries. Results are compared with those of published RCTs.

中文翻译：

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观察性研究设计在比较有效性研究中的重要性：来自 GARFIELD-AF 和 ORBIT-AF 登记处的经验教训。

随机对照试验 (RCT) 被认为是评估治疗效果的黄金标准。然而，在许多情况下，由于时间限制、成本限制或道德原因，它们是不切实际的。因此，非随机观察性研究在比较有效性和安全性研究中具有重要作用，因为它们可以解决使用传统 RCT 方法无法解决的问题。可以通过模仿等效但理想的随机试验（目标试验）的设计原则来战略性地设计观察性研究，以降低潜在偏倚来源的风险，这将回答感兴趣的研究问题。在本文中，我们回顾了在目标试验仿真框架内进行有效因果推理所需的观察性研究的一些必要组成部分，以避免研究设计中常见的方法论缺陷。我们讨论了一致性、零时间规范、可交换性和积极性的假设。为了在现有知识通过临床试验充分确立的背景下说明这些概念，我们从两个真实世界评估和比较维生素 K 拮抗剂 (VKA) 与无 VKA (No VKA) 治疗心房颤动的效果观察性研究，即 GARFIELD-AF 和 ORBIT-AF 登记。将结果与已发表的 RCT 进行比较。时间零规格，可交换性和积极性。为了在现有知识通过临床试验充分确立的背景下说明这些概念，我们从两个真实世界评估和比较维生素 K 拮抗剂 (VKA) 与无 VKA (No VKA) 治疗心房颤动的效果观察性研究，即 GARFIELD-AF 和 ORBIT-AF 登记。将结果与已发表的 RCT 进行比较。时间零规格，可交换性和积极性。为了在现有知识通过临床试验充分确立的背景下说明这些概念，我们从两个真实世界评估和比较维生素 K 拮抗剂 (VKA) 与无 VKA (No VKA) 治疗心房颤动的效果观察性研究，即 GARFIELD-AF 和 ORBIT-AF 登记。将结果与已发表的 RCT 进行比较。