PROactive: A Sad Tale of Inappropriate Analysis and Unjustified Interpretation

Abstract

T he results of the Prospective Pioglitazone Clinical Trial in Macrovascular Events (PROactive) study1 have stimulated much discussion in both the diabetes and cardiovascular communities. The official commentary of the American Diabetes Association (ADA) was published in Diabetes Care 2 and is reprinted in this issue of Clinical Diabetes (p. 66). Previously, I offered a different view of PROactive in another ADA publication, DOC News ,3 from which this commentary is adapted. My earlier comments generated a flood of e-mails, a few of which claimed I was a naysayer or curmudgeon, but the majority of which expressed agreement with my views. Other commentaries have been published by Yki-Jarvinen4 as an accompanying article in the same issue of Lancet in which the PROactive study appeared, Freemantle5 in the British Medical Journal , and Ceriello6 in Diabetic Medicine . These commentaries focus on different points, but there are a number of commonalities among them. PROactive was a much-anticipated study because it was the first large study to be reported that was designed to determine whether the potential theoretical benefits of peroxisome proliferator-activated receptor-γ (PPAR-γ) agonists (in this case pioglitazone) on endothelial function and cardiovascular risk markers might indeed result in fewer macrovascular disease (atherosclerosis) events in patients with type 2 diabetes. That anticipation was driven by a considerable amount of hype and by the 2004 publication of the study's design and baseline data in Diabetes Care .7 An entire hour was allocated for the PROactive presentation on 12 September 2005 during the annual meeting of the European Association for the Study of Diabetes (EASD) in Athens, Greece, and the presentation was webcast worldwide.8 The publication of the study's results in Lancet occurred < 1 month later.1 PROactive researchers had enrolled 5,238 patients at 321 …