Friday, February 26, 2010

Revisiting Avandia and personal attacks against Dr. Mintz

Almost 3 years after the safety hoopla raised by Nissen's NEJM meta-analysis the issue has resurfaced. It seems a report on the Avandia controversy by Senators Grassley and Baucus was recently made public and covered by the New York Times. The Times piece was distorted and inaccurate (maybe I'll write a separate post about that later) and uncovered nothing new.

That prompted Dr. Mintz, who has written a great deal about it before, to reassess the controversy in his blog and as a guest blogger over at the Forbes health blog, The Science Business. He reviewed the evidence and pointed out that there's nothing new in the discussion concerning the risks and benefits of Avandia. Then Retired Doc, citing Mintz's analysis, asked readers why we're stirring the pot again. He got one response to his question and that was from Dr. Roy Poses at Health Care Renewal:

Perhaps Dr Mintz may have been influenced by his financial ties to GSK (not disclosed in his blog post that you linked to, but now mentioned in the Forbes Science Business blog version of it, see here:

The undisclosed conflicts were first noted in the PharmaLot blog, see here:

Dr. Poses's response is troubling in a way that is typical when issues of science are thrown into the arena of popular debate. At best it confuses things by conflating questions about Avandia's safety with those concerning the ethics of Dr. Mintz. Or, worse, it may represent the intellectually lazy approach of applying a simple litmus test (Pharma ties) to summarily reject Dr. Mintz's analysis. That sort of ad hominem attack may rarely be justified if ones opponent makes baseless claims without pointing to primary sources of evidence. While Dr. Mintz's analysis is not a systematic review it did appeal to primary sources. There is more than sufficient warrant to accept or reject Dr. Mintz's argument on its own merits. Personal attacks in this case are inappropriate and unnecessary.

Meanwhile over at Pharmalot (linked above by Dr. Poses) the whole thing morphed into a full-scale attack on Dr. Mintz---not so much in the body of Ed Silverman's post, but in the comments. And, to be fair to Silverman, he wrote with a singular focus and made no pretense of evaluating Avandia.

For those readers who take me at my word that I have no Pharma ties (not all readers do!) here's my skinny on type 2 diabetes treatments starting with the categories associated with greatest harm down to the ones with greatest benefit:

Known macrovascular harm

Probable macrovascular harm (Dose and usage pattern related)

Question raised about macrovascular harm without convincing evidence
Rosiglitazone (Avandia)

Preliminary evidence of macrovascular benefit, in need of confirmatory data

Probable macrovascular benefit
Pioglitazone (Actose)

Definite macrovascular benefit
Diet, exercise

No evidence to guide clinicians as to macrovascular benefit, harm or neutral effect
All other agents!

Note that this listing is not a treatment algorithm (you can find that here). It is only concerned with macrovascular effects of diabetes treatments, because that's the focus of the current controversy. It ignores other benefits of glycemic control such as microvascular benefit.

On a related note, another area of obfuscation by the popular media and even some physician writers (who should know better) is the confusion of macrovascular harm with the heart failure issue. Although TZDs cause fluid retention and there are heart failure concerns the evidence is now clear that it is a peripheral effect with no direct adverse effect on the heart. This was well illustrated in a study which showed that although Avandia was associated with increased need for treatment of edema there was no finding of adverse cardiac effect as evidenced by lack of change in cardiac ejection fraction.

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