As emphasized by the Institute of Medicine, the effectiveness of more than half of therapies used in clinical practice is unclear. High priority should be given to promoting comparative effectiveness (CE) trials, trials of alternative therapies performed to facilitate better informed and more evidence-based decisions by clinicians, patients, third-party payers, and policy makers.2,3  In such trials, the effectiveness of different treatment options is assessed under usual clinical circumstances across a broad range of patients treated clinically with these therapies. CE trials provide essential information to improve outcomes in everyday clinical practice that cannot be obtained from trials performed to assess the efficacy of a new experimental therapy. Such trials are conducted in ideal or restricted circumstances; enroll a limited number of carefully selected, and often uncomplicated, patients; and thus generally yield an optimistic view of efficacy. In comparing alternative therapies already used in clinical practice, CE...

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