An application of the Causal Roadmap in two safety monitoring case studies: Causal inference and outcome prediction using electronic health record data
This paper highlights the use of real-world data in healthcare regulation, focusing on the Causal Roadmap framework for transparent and objective analysis. It demonstrates through two case studies how the framework aids in drug safety monitoring and clinical phenotyping, ensuring reproducibility and transparent decision-making in healthcare surveillance.
Sensitivity Analysis for Causality in Observational Studies for Regulatory Science
This article discusses the importance of real-world data (RWD) in regulatory science, as highlighted by the 21st Century Cures Act which mandates FDA guidance on its use. It focuses on a key aspect of the causal roadmap, a recommended framework for designing studies with RWD: sensitivity analysis. Sensitivity analysis tests the robustness of conclusions against assumptions in the causal roadmap. The paper provides a practical example from a study on Nifurtimox's effectiveness in treating Chagas disease and reviews various methods for sensitivity analysis in causal inference, emphasizing their practical application for regulatory purposes.
A Causal Roadmap for Generating High-quality Real-world Evidence
This paper highlights the increasing use of real-world evidence (RWE) in clinical and regulatory decision-making, noting the lack of detailed guidance in many RWE proposals which leads to flawed methodologies and misinterpretations of real-world data (RWD). It introduces the Causal Roadmap as a detailed framework to help investigators predefine study designs and analysis plans, promoting transparent evaluation and objective comparisons. The Roadmap assists in producing high-quality RWE and facilitates effective communication with regulatory agencies. The paper, along with three companion pieces, aims to popularize the Causal Roadmap among clinical researchers, showcasing its practical applications.
Case Study of Semaglutide and Cardiovascular Outcomes: An Application of the Causal Roadmap to a Hybrid Design for Augmenting an RCT Control Arm with Real-World Data
This study evaluates cardiovascular risks associated with oral semaglutide using real-world data (RWD), employing the Causal Roadmap across three designs: randomized controlled trials, a single RCT, and a hybrid design integrating RCT and RWD. It assesses design efficacy, finding similar results for the RCTs and varied outcomes for the hybrid design based on bias. The hybrid approach, applied to real data, suggests oral semaglutide's potential in reducing cardiovascular risks. This highlights the Causal Roadmap's effectiveness in minimizing RWD study biases and aiding in design comparisons, emphasizing oral semaglutide's efficacy in cardiovascular risk management.