LAUSR

The emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and the COVID-19 pandemic in 2020 created unprecedented global challenges to existing models of evidence evaluation. COVID-19 was recognized as being associated with a high incidence of thrombotic complications. In the absence of identi fi ed therapies, an imperative emerged to rapidly initiate therapeutic clinical trials in the domains of hematology and thrombosis. COVID-19 presented unique challenges, including a rapidly evolving virus, heterogeneous host response, limited mechanistic insight, disproportionate impact upon vulnerable and underrepresented patient populations, and an urgent need to identify widely available therapies to address the global pandemic. Designing randomized clinical trials (RCTs) that incorporated these and other complexities was an evolving concept when the COVID-19 pandemic began, at which time the imperative to conduct ef fi cient, nimble, reproducible, pragmatic, and impactful clinical trial designs became immediate. The fi rst recognized double-blind RCT, conducted in 1943, was similarly designed to address patient and population needs in a viral illness — the common cold. 1 The fundamental importance of randomization in reducing systematic bias in interventional trials is deeply rooted and widely accepted in medicine. 2 Thus, the RCT has taken its place as the gold standard for establishing causation in clinical research. Although our understanding of diseases and the practice of medicine have substantively evolved over time, the design and conduct of RCTs, despite their obvious limitations, have continued with little adaptation. Conventional, evidence.