The Gap Between Clinical Trials and Clinical Practice: The Use of Pragmatic Clinical Trials to Inform Regulatory Decision Making

Drug use in clinical practice often deviates from the carefully scripted use in controlled clinical trials or the evidence-based guidance in drug labels. The prescribers' judgments may result in a wider spectrum of disease being treated, including those in patients with more comorbidities. Prescribed doses, as well as patient compliance and adherence, may differ from the experience in the classical clinical trial setting. This may result in an unanticipated (and unfavorable) shift in the benefit-to-risk ratio when the drug is used in general practice. Pragmatic, or naturalistic, clinical trials balance efforts to reflect the practice environment with the need to collect data that robustly inform decision making. Increased use of pragmatic trials has been advocated to support public policy decisions, third-party reimbursement decisions, and decision making by physicians. Pragmatic trials have the potential to better inform drug approval decisions by providing a better understanding of the drug's likely efficacy and safety in the marketplace. Clinical Pharmacology & Therapeutics (2010) 87 3, 351–355. doi:10.1038/clpt.2009.218