Response to the Nashville Scene's Mr. Hargove's Posted Crticism December 8, 2010

In response to Mr. Hargove comment:

I'm also going to call Dr. Roseman out on his insistence that randomized clinical trials are the only way to judge Avandia (which was clearly contradicted in Glaxo internal memos). Given his education, Dr. Roseman should know that these kinds of clinical trials aren't designed to assess risk. They're designed to assess benefit. You'd have to have an impossibly massive trial to gauge risk. When he misleadingly points to the "insignificant risk," he fails to note that when that risk is spread out over the 23 million diabetes patients in the country, you have some serious numbers. The intent of the article isn't to villainize Dr. Roseman, but to question the close relationship he and others have with the industry. It's worth discussing why he would so steadfastly defend the drug of a company that pays him well when all indications point to its very real danger.

In this response, I will deal with the second of your criticisms, which I have copied above. First of all, please show in my writings or presentations that I asserted that the only way to examine the safety of a drug is through randomized clinical trials alone? Secondly, please show me what GSK internal memos to which you are referring that “clearly” contradict my alleged comment that “randomized clinical trials are the only way to judge Avandia”.

My so-called defense of Avandia, a “drug of a company that pays [me] well” is based upon solid science. As an academically minded physician, I feel that the scientific issues of safety of Avandia are far from settled. Contrary to you insinuation, Mr. Hargrove, my opinions cannot be bought. From a personal standpoint, I have not recognized any direct cardiovascular harm to my patients during my twelve years of experience of prescribing Avandia.

If your article is not meant to villainize me, why is it that you continue to take out of context my statements about the Avandia safety issue and to insinuate that my opinions are biased as a result of the patronage of the pharmaceutical industry? I have fully disclosed my position. I have made available to you my writings on this issue, which you have failed to include in your report: http://www.cardiologywellness.net/CWC/Writings.html, I have never stated that a signal about cardiovascular safety around Avandia dose not exists. Just to reiterate, the scientific evidence for affirming cardiovascular risk to Avandia is incomplete and conflicting. The observational studies, in their totality, have suggested that Avandia use may be linked to a small risk (which I called “insignificant”, not in statistical terms but in terms of absolute risk). (For the readers, the nature of observational studies is described at: http://en.wikipedia.org/wiki/Observational_study.) However, the experimental or randomized clinical studies (for definition: http://en.wikipedia.org/wiki/Randomized_controlled_trial) did not support this conclusion and in the case of two studies, VADT and BARI-2D, which was not funded by the pharmaceutical industry but by the United States government, actually suggested a benefit!

Not acknowledged in your article or your blog, my views comport with that of the American College of Cardiology, the American Heart Association, and even the FDA. Let’s take a look at the facts. In the FDA (Food and Drug Administration) ruling on Avandia, Dr. Woodcock, director of the Center for Drug Evaluation and Research (CDER), stated, “the cardiovascular safety profile of rosiglitazone is still an open question because there are conflicting data on the existence and magnitude of the risk.”[i] This conclusion is similar to the FDA’s position in 2007, “In their entirety, the available data on the risk of myocardial ischemia are inconclusive.”[ii] Recently, in a 2010 update, the American College of Cardiology and the American Heart Association jointly reviewed the safety issue of thiazolidinediones and issued a statement, which concluded similarly, “In summary, an association between rosiglitazone [Avandia] and IHD [ischemic heart disease] outcomes has not yet been firmly established.”[iii] Contrary to your implied depiction of me in this article, I am not alone in my viewpoints. I believe that my viewpoint is credible and defensible, regardless of the appearance of bias related to my GSK association.

Now, lets return to your point about the nature of evidence in determining causation. Your attempt to discredit my viewpoints by quoting an unnamed source is obvious. “Given his education, Dr. Roseman should know that these kinds of clinical trials aren't designed to assess risk. They're designed to assess benefit.” Your statement is a simple distillation and dilution of a difficult issue in science, which in all due respect, you are not qualified to comment. Again I would refer to my writing on this subject included at http://www.cardiologywellness.net/CWC/Writings.html. I have enclosed an addendum, which is a part of my commentaries, which offers a complete response to this issue. Again, your attempts at pseudo-scientific reporting are showing. None other than the FDA’s own Dr. Woodcock disagreed with your insinuation that the randomized clinical trials to which I referred was in somehow inadequate in answering the question of cardiovascular safety of Avandia. In her previously mentioned statement, she exclaimed, “The most reliable evidence about clinical outcomes comes from well-conducted, randomized trials.”

Contrary to your comment, the results of the observation studies were conflicting, despite your suggesting their superiority over randomized clinical trials, For example, the three observational studies on the elderly, including one authored by the FDA’s analyst, Dr. David Graham (http://jama.ama-assn.org/content/304/4/411.abstract), did not show any significant difference in heart attacks among the users of Avandia. The studies did suggest an increase in total mortality, which the preponderance of the observation studies have not.

These observations formed the basis of the FDA’s restricted, not banned, use of Avandia. By the way, if the FDA was so convinced in Dr. Fugh-Berman and your point of view, don’t you think that the FDA would have removed the drug from the US formulary? They did not; they restricted it use until the RECORD safety trial can be reanalyzed.

Again, Mr. Hargove, your one-sided reporting is apparent. These issues, on which you are attempting to report, are complex and warrant more thorough and thoughtful reporting than your sensational snippets that you throw out to your readership in an attempt to push your particular agenda about a news issue. Again, your bias against the pharmaceutical industry has now been fully disclosed. Why don’t you report at least in passing some positive aspects of your subject matter? It would give some balance and credibility to your reporting.

I believe the problem here, a fundamental one in your so-called investigative reporting, is that you get a hold of a “hook” of a story, in this case my defense of Avandia for a company that employs my lecturing services, and create controversy around this news issue, in this case the influence of the pharmaceutical industry. As a passing note, even if we accept your premise that pharmaceutical industry is “pushing” its drugs, what is the harm? The only damages appear that physicians are either overtly or subtlety converted to using the company’s branded drugs, which have been certified as being both efficacious and safe by the FDA. So what is the rub, that the pharmaceutical industry is attempting to make a profit from their innovations and discoveries?

Your purpose seems not to analyze objectively a newsworthy story but to create a buzz in the news media for the purposes of drawing attention to your article. Despite my statements and published views on the issue, you continue to misrepresent my perspective on Avandia. Your presenting my alleged irremovable faith in Avandia, despite “all indications point[ing] to its real danger”, makes for a good headline about the influence of money by the pharmaceutical industry. But, it is not the valid story! Your continued manipulation of the true kernel of the story reveals you for who you are, a polemicist and not an objective reporter. Certainly, your depiction of me is demeaning, and your purposeful effect, contrary to your protestation, is to “villainize” me for the purpose of news sensationalism.

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[i]                   http://www.fda.gov/downloads/Drugs/DrugSafety/PostmarketDrugSafetyInformationforPatientsandProviders/UCM226959.pdf [assessed on December 5, 2010]

[ii]                   
FDA adds boxed warning for heart-related risk to antidiabetes drug Avandia "press release#. Silver Spring, Md: Food and Drug Administration; November 14, 2007. Available at: http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/2007/ucm109026.htm.

[iii]                   
Kaul S, et al., Thiazolidinedione Drugs and Cardiovascular Risks: A Science Advisory From the American Heart Association and American College of Cardiology Foundation. Circulation. 2010;121:1868-1877. Copy available at: http://circ.ahajournals.org/cgi/reprint/CIR.0b013e3181d34114