Keywords: Pragmatic design, randomized controlled trials, comparative effectiveness, real-world evidence, methods guidance
RCTs often serve the purpose of assessing the efficacy and safety of a compound. Combining real-world evidence and randomization, pragmatic randomized clinical trials (PrCT) can be used to inform treatment effectiveness and healthcare decisions. PrCTs, referring to studies where several pragmatic elements are used (eligibility, endpoints, follow-up, etc.), pose unique challenges [Loudon, 2015]. From a literature review, we propose a definition of PrCT and discuss strategies to overcome some PrCT challenges. For example, uncertainties related to alternative data collection mechanisms (e.g., via electronic health records) and absence of blinding could lead to potentially non-random missing data in study endpoints such that randomization is no longer protected by intent-to-treat. More complex randomization strategies may be needed to minimize bias. Additional data sources could be used to synthesize information and create a more accurate endpoint definition, which may require tools such as natural language processing. The statistician must become familiar with the challenges and strengths of PrCT from design to analysis to interpretation to transform data into evidence [Califf, 2016].