How good is "Evidence" from clinical studies of drug effects and why might such evidence fail in the prediction of clinical utility of drugs

Promising evidence from clinical studies of drug effects does not always translate to improvements in patient outcomes. In this review, we discuss why early evidence is often ill suited to predict the clinical utility of drugs. The current gap between initial drug effects and their subsequent clinical utility results from deficits in the design, conduct, analysis, reporting, and synthesis of clinical studies – often creating conditions for generating favorable estimates for drug effects. There are potential solutions to improve the relevance of clinical evidence in predicting the real-world effectiveness of drugs. What is needed is a new emphasis on clinical utility, with nonconflicted entities playing a greater role in the generation, synthesis, and interpretation of clinical evidence. Clinical studies should adopt strong design features; reflect actual clinical practice; and evaluate outcomes and comparisons that are meaningful to patients. Transformative changes to the research agenda may generate more meaningful evidence on drug effects to guide clinical decision-making.