Randomized assignment of treatment excludes reverse causation and selection bias and, in sufficiently 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 sufficient numbers of patients, provide the most valid results. Although conceptually straightforward, design of clinical trials requires thoughtful trade-offs among competing approaches—all of which influence the number of patients required, enrollment time, internal and external validity, ability to evaluate interactions among treatments, and cost.
From the *Department of Outcomes Research, Anesthesiology Institute, Cleveland Clinic, Cleveland, Ohio; and †Department of Quantitative Health Sciences, Lerner Research Institute, Cleveland Clinic, Cleveland, Ohio.
Accepted for publication May 1, 2015.
Funding: Supported by internal sources.
The authors declare no conflicts of interest.
Address correspondence to Daniel I. Sessler, MD, Department of Outcomes Research, Cleveland Clinic, 9500 Euclid Ave./P77, Cleveland, OH 44195. Address e-mail to DS@OR.org; www.OR.org.