Simple Principles of Clinical Trials Remain Powerful

摘要

N THIS ISSUE OF JAMA, 2 ARTICLES FROM THE CLINICAL Trial of Reviparin and Metabolic Modulation in Acute Myocardial Infarction Treatment Evaluation (CREATE) greatly enhance the knowledge base for the treatment of acute ST-segment elevation myocardial infarction (STEMI).1'2 Yet, as with all good clinical trials, this study raises new questions and perspectives that deserve further consideration.The factorial design of the CREATE trial proves 2 points: (1) low-molecular-weight heparin reduces mortality and ischemic events in STEMI and (2) the age-old argument about glucose, insulin, and potassium (GIK) therapy can be put to rest-this treatment does not work in STEMI. The CREATE trial is powerful and definitive on both counts. However, the conduct and results of the trial stimulate thoughts about several questions.Do the Principles of Pragmatic Clinical Trials3-4 Still Hold in This Era of "Personalized Medicine"? Despite ongoing efforts to develop more targeted approaches to therapeutics using biomarkers and genomics, the majority of therapies for complex diseases act through mechanisms that are not specifically targeted. Accordingly, a trial of adequate size to show modest but important effects on true clinical outcomes must remain the standard for the evidence on which therapies are based. In fact, it is easy to postulate many mechanistic reasons why either of the therapies tested in CREATE would or would not "work," but the definitive proof requires an accounting of the risks and benefits using the "big 4" measures: length of life, quality of life, discrete negative events, and costs.