I regret that the PROactive Study Group has taken the view that I had“reiterated” an opinion of misconduct on their part after they had clarified the situation. My first commentary appeared in DOC News in December 2005 and was written at the request of its editor, Dr. Irl Hirsch. My second commentary was adapted from the first at the request of then-editor of Clinical Diabetes, Dr. Jennifer Marks. It was submitted on 14 January 2006 and appeared in the February 2006 issue. The PROactive Study Group response to my commentary in DOC News was apparently submitted on 24 February 2006 and was forwarded to me by Dr. Hirsch on 13 March 2006. Thus, my Clinical Diabetes commentary appeared prior to my seeing the PROactive Study Group explanation of the details surrounding the creation of the “principal secondary end point.” I accept their explanation,which is actually more detailed in their current letter. I am sorry that the writers believe that I have impugned their integrity. That was not my intent.
I should note, however, that my commentary emphasized many other aspects of the PROactive study:
The lack of consistency across all cardiovascular outcomes
The difference in A1C between the two groups, rendering it impossible to attribute the results to pioglitazone per se, as opposed to better glycemic control
The fact that benefits were only seen in those subjects not taking statins
The increased complications in the pioglitazone group, including congestive heart failure, weight gain, and edema
The inappropriate generalization of “benefits” to all patients with diabetes
The fact that because the primary end point was negative, the study was a negative study
As for my “undeclared reasons” for having difficulty accepting PROactive, I believe that numbers 1 to 6 above (detailed in my commentary)provide a legitimate basis for challenging the conclusions asserted by the investigators. Moreover, I find the marketing of the PROactive results in a precedent-setting number of talks across North America to lack fair balance in not addressing the issues raised by me and by a number of other commentators referenced in my commentary. It was this marketing onslaught that stimulated the editors (Drs. Hirsch and Marks) to ask for my comments. I appreciate that the PROactive investigators have not been involved in this marketing exercise and may not realize the extent of concern that it has caused many in the U.S. diabetes community.