Clinical trials (CTs) are the cornerstone of clinical medicine. Besides providing definitive tests for drug efficacy and authoritative guidance for treatment, they reveal disease and drug mechanisms in humans and confirm (or refute) ideas derived from preclinical research (1, 2). Unfortunately, in neurology and psychiatry, CTs may not perform these tasks as well as they should. Their usefulness and validity are often compromised by methodological inadequacies: measurement errors (3–5), analysis and interpretation biases (6, 7), selective reporting and publication (8), inadequate preclinical and early clinical preparations (9, 10), and late-stage protocol modifications (6). These problems result in drug and CT failures, underestimations of effect sizes, and—probably the most unfortunate outcome—information of limited value to clinicians.
