Randomized assignment of treatment excludes reverse causation and selection bias and, in suffciently large studies, effectively prevents confounding. Well-implemented blinding prevents measurement bias. Studies that include these protections are called randomized, blinded clinical trials and, when conducted with suffcient numbers of patients, provide the most valid results. Although conceptually straightforward, design of clinical trials requires thoughtful tradeoffs among competing approaches—all of which infuence the number of patients required, enrollment time, internal and external validity, ability to evaluate interactions among treatments, and cost.