Advancing the role of real-world evidence in comparative effectiveness research

Aim: Comparative effectiveness research (CER) is essential for making informed decisions about drug access. It provides insights into the effectiveness and safety of new drugs compared with existing treatments, thereby guiding better healthcare decisions and ensuring that new therapies meet the real-world needs of patients and healthcare systems. Objective: To provide a tool that assists analysts and decision-makers in identifying the most suitable analytical approach for answering a CER question, given specific data availability contexts. Methods: A systematic literature review of the scientific literature was performed and existing regulatory and health technology assessment (HTA) guidance were evaluated to identify and compare recommendations and best practices. Based on this review a methods flowchart that synthesizes current practices and requirements was proposed. Results: The review did not find any papers that clearly identified the most appropriate analytical approach for answering CER questions under various conditions. Therefore, a methods flowchart was designed to inform analyst and decision makers choices starting from a well-defined scientific question. Conclusion: The proposed methods flowchart offers clear guidance on CER methodologies across a range of settings and research needs. It begins with a well-defined research question and considers multiple feasibility aspects related to CER. This tool aims to standardize methods, ensure rigorous and consistent research quality and promote a culture of evidence-based decision-making in healthcare.