More on the Avandia Debate: Common Sense vs. the Statisticians
I previously addressed the issue of â€œrelative riskâ€ in this blog, as it applies to the perceived hazard of using Avandia (rosiglitazone) to treat diabetics. To gain a better understanding of the true Avandia risk, I went back to the actual data submitted by Dr. Nissan et. al. in the meta-analysis which ignited this controversy. What I found supports my notion that the real risk is allowing statisticians to bludgeon common sense into immediate submission with a few technical terms.
In Nissanâ€™s meta-analysis of 42 studies which compared Avandia to other diabetes treatments (â€œotherâ€), results from a total of 27,843 diabetics were analyzed (15,560 received Avandia and 12,283 â€œotherâ€ treatments). During the study period there were a total of 158 heart attacks (M.I.â€™s) and 58 deaths from cardiovascular causes. Compared to â€œotherâ€ treatments there were 14 extra M.Iâ€™s in the Avandia group then the â€œotherâ€ group. If your first reaction is â€œgeeâ€¦14 extra deaths seem unacceptableâ€, remember there were 2300 more people in the Avandia group for bad things to happen toâ€¦.see the blog on â€œrelative riskâ€ for more on that issue).
The over-all incidence of cardiovascular death for diabetics in the U.S. is generally accepted as 65% or more and the incidence of heart attack (M.I.) substantially higher. In Nissanâ€™s study of 27,843 total diabetics 65% is equivalent to 17,730 total M.I.â€™s. The 14 extra M.I.â€™s in the Avandia group would make the M.I. rate 65.09%. Not a very alarming increase if it were true. In the â€œotherâ€ group if we equalize for the smaller number of participants in that group, we find the M.I. incidence would be higher at 65.12%. ( 72 M.I.â€™s for Avandia, 91 M.I.â€™s for â€œotherâ€ treatment).
Another way to look at the magnitude of the supposed increase in Avandia related events,
we find the â€œexcessâ€ number of M.I.â€™s is equivalent to 1 per 1250. For practitioners who treat diabetes and understand the enormous degree of variation between diabetic patients, trying to pin-point the factors accounting for one M.I. per 1250 in this group would be like trying to isolate one snowflake in a blizzard.
I simply do not believe that there is a way to validate the results of Nissanâ€™s study. Believing the use of statistics can correctly pin-point the cause of 1 in 1250 M.I.â€™s within the chaos that is diabetes care, in my opinion, is being naÃ¯ve to the true complexity of this disease and its treatment.
Gary Pepper, M.D.