The Current Landscape in Biostatistics of Real-World Data and Evidence: Clinical Study Design and Analysis

Propensity‐score‐based meta‐analytic predictive prior for incorporating real‐world and historical data

“…For example, propensity score methods, matching/stratification/weighting, have been widely used for indirect comparison while reducing confounding bias in single‐arm phase oncology trials where a control cohort is absent due to ethical considerations. Another major and important application of leveraging external data is in rare disease trials where required sample sizes are infeasible to reach due to scarcity of the eligible population 3,4 . In such scenarios, utilizing innovative methods of incorporating RWD and historical data may potentially reduce the sample size, shorten the duration of clinical trials, and accelerate patient access to life‐saving medicines.…”

Comment on “Biostatistical Considerations When Using RWD and RWE in Clinical Studies for Regulatory Purposes: A Landscape Assessment”

“…We thank and commend Dr. Levenson and colleagues for their insightful overview and are grateful for the opportunity to discuss their excellent article (Levenson et al, 2021). We would also like to congratulate its companion papers led by Dr. Chen and Dr. Ho (Chen et al, 2021;Ho et al, 2021). These papers provide clear and detailed explanations of the biostatistical considerations when using real world data (RWD) in regulatory submissions.…”

“…In using RWD, it is critical to understand biostatistical considerations from a scientific point of view as well as regulatory, data reliability and ethical points. In Levenson et al's (2021) and the companion papers (Chen et al, 2021;Ho et al, 2021), the authors introduced the study designs and analysis methods of clinical trials using RWD, summarized the typical biases to be considered when using these designs, and presented how to set the estimand(s) in an easy-tounderstand manner. In addition, Ho et al (Ho et al, 2021) provided a detailed explanation of the Causal Roadmap as a statistical inference framework for obtaining real world evidence (RWE).…”

“…For example, a joint task force of the International Society for Pharmacoeconomics and Outcomes Research (ISPOR) and the International Society for Pharmacoepidemiology (ISPE) has reported on good practice to maintain transparency in conducting clinical research using RWD (Berger et al, 2017;ISPOR, 2019;Wang et al, 2017). As a specific approach to utilize RWD for an external control, Levenson et al (2021) and its companion papers (Chen et al, 2021;Ho et al, 2021) also introduced the "two-step" approach proposed by Yue et al (2014), which implements propensity score analysis to adjust for covariate-difference between external control from RWD and a study sample. In a "design stage", analysts who are not allowed to access outcome data select candidate covariates and choose propensity score models possibly referring to model-fit measures.…”

“…In our working group, we have focused on the biases inherent in the use of RWD as an external control in single arm trials and hybrid control approaches in RCTs; we summarized those bias in terms of information bias, selection bias, and confounding bias. Levenson et al (2021) and Chen et al (2021) also provided a detailed description of those biases and corresponding analysis methods, including their pros and cons.…”