Putnam Data Sciences, LLC, Cambridge, MA, USA.
Division of Biostatistics, University of California at Berkeley, Berkeley, CA, USA.
BMC Med Res Methodol. 2023 Aug 2;23(1):178. doi: 10.1186/s12874-023-01998-2.
The Targeted Learning roadmap provides a systematic guide for generating and evaluating real-world evidence (RWE). From a regulatory perspective, RWE arises from diverse sources such as randomized controlled trials that make use of real-world data, observational studies, and other study designs. This paper illustrates a principled approach to assessing the validity and interpretability of RWE.
We applied the roadmap to a published observational study of the dose-response association between ritodrine hydrochloride and pulmonary edema among women pregnant with twins in Japan. The goal was to identify barriers to causal effect estimation beyond unmeasured confounding reported by the study's authors, and to explore potential options for overcoming the barriers that robustify results.
Following the roadmap raised issues that led us to formulate alternative causal questions that produced more reliable, interpretable RWE. The process revealed a lack of information in the available data to identify a causal dose-response curve. However, under explicit assumptions the effect of treatment with any amount of ritodrine versus none, albeit a less ambitious parameter, can be estimated from data.
Before RWE can be used in support of clinical and regulatory decision-making, its quality and reliability must be systematically evaluated. The TL roadmap prescribes how to carry out a thorough, transparent, and realistic assessment of RWE. We recommend this approach be a routine part of any decision-making process.
靶向学习路线图为生成和评估真实世界证据（RWE）提供了系统的指导。从监管的角度来看，RWE 来自于多种来源，如利用真实世界数据的随机对照试验、观察性研究和其他研究设计。本文说明了一种评估 RWE 的有效性和可解释性的原则性方法。
我们将路线图应用于一项已发表的观察性研究，该研究在日本对双胞胎孕妇使用盐酸利托君与肺水肿之间的剂量反应关系进行了研究。目的是确定除研究作者报告的未测量混杂之外对因果效应估计的障碍，并探讨使结果更稳健的潜在克服障碍的选择。
遵循路线图提出的问题使我们提出了替代性的因果问题，从而产生了更可靠、更易解释的 RWE。该过程显示，在可用数据中缺乏识别因果剂量反应曲线的信息。然而，根据明确的假设，可以从数据中估计出任何剂量的利托君与不使用任何剂量的利托君治疗的效果，尽管这是一个不太有野心的参数。
在 RWE 能够支持临床和监管决策之前，必须对其质量和可靠性进行系统评估。TL 路线图规定了如何对 RWE 进行彻底、透明和现实的评估。我们建议将这种方法作为任何决策过程的常规部分。
