The Avandia Spin Cycle Continues Even After the FDA Safety Hearings

We have posted multiple times about Avandia (rosiglitazone), GlaxoSmithKline's star-crossed glucose-lowering drug.  While Avandia has received considerable media coverage, we focused on two questions: 1 - what are the benefits and harms of rosiglitazone as a treatment of type 2 diabetes, and therefore for which patients under what circumstances should this drug be used? 2 - what barriers have prevented physicians and patients from getting the best possible answer to the first question, and what can be done about them?  (See recent post <a href="http://hcrenewal.blogspot.com/2010/02/bring-back-dsi-avandia-case-as-spy.html">here</a>.)  <br /><br />In particular, the Avandia case has illustrated how those with vested interests in the success of a health care product have done their best to obscure information that might threaten its success, even when doing so obscures the information that physicians and patients need to make the best possible decisions.  At one point, (in 2007, no less) we called this the "<a href="http://hcrenewal.blogspot.com/2007/06/avandia-spin-cycle-continues.html">Avandia spin cycle</a>."<br /><br />Avandia once again has been in the news after the US Food and Drug Administration's hearings on the safety of the drug.  These hearings were so well covered in the media that a lengthy summary would be superfluous.  However, their main points demonstrated the persistence of the Avandia spin cycle:<br />- An FDA reviewer felt that "the company's misreadings of the ... Record trial ... were so profound, he concluded, that they 'suggest <em>serious flaws with trial conduct</em>.'" (per Gardiner Harris <a href="http://www.nytimes.com/2010/07/10/health/10diabetes.html">writing</a> in the New York Times)<br />-A former FDA reviewer "<em>withheld from regulators</em> a study showing its Avandia diabetes drug may cause heart attacks." (<a href="http://www.bloomberg.com/news/2010-07-09/glaxo-withheld-avandia-study-former-fda-manager-said-to-testify-in-suit.html">per Bloomberg News</a>)<br />- GlaxoSmithKline's forerunner SmithKline Beecham "secretly began a study to find out if its diabetes medicine, Avandia, was safer for the heart than a competing pill, Actos, made by Takeda."  However, "the study also provided clear signs that it [Avandia] was riskier to the heart.  But instead of publishing the results, the company spent the next 11 years <em>trying to cover them up</em>." (per Gardiner Harris <a href="http://www.nytimes.com/2010/07/13/health/policy/13avandia.html">writing</a> in the New York Times.<br />- "Government experts and a panel of medical advisers repeatedly voiced <em>skepticism on Tuesday about the trustworthiness of GlaxoSmithKline</em>, which makes the controversial diabetes drug Avandia." (per Gardiner Harris again <a href="http://www.nytimes.com/2010/07/14/health/policy/14diabetes.html">writing</a> in the New York Times.)<br /><br />So the Avandia saga has brought to the front pages the concerns we have had with <a href="http://hcrenewal.blogspot.com/search/label/suppression%20of%20medical%20research">suppression</a> and <a href="http://hcrenewal.blogspot.com/search/label/manipulating%20clinical%20research">manipulation</a> of clinical research, especially when pursued by health care organizations with vested interests in the results of specific research projects coming out a certain way, and how they have been enabled by those with <a href="http://hcrenewal.blogspot.com/search/label/conflicts%20of%20interest">conflicts of interest</a>.  Doctors thus should be worried whether those of us who try to practice evidence-based medicine have been fooled into practicing <a href="http://hcrenewal.blogspot.com/search/label/pseudo-evidence%20based%20medicine">pseudo-evidence-based-medicine</a>.<br /><br />Those commenting on the story focused on the need for transparency when clinical research is funded and run by the corporations whose products are being evaluated.<br />-  "GlaxoSmithKline, the maker of Avandia, can't be trusted to report adverse clinical results fairly.  The company must be <em>watched like a hawk </em>as additional trials that it sponsors go forward."  (<a href="http://www.nytimes.com/2010/07/15/opinion/15thu1.html">NY Times editorial</a>)<br />-  "What America should demand in return for ... [generous patent] protection is that the FDA be able to make an <em>honest evaluation of the efficacy of drugs</em>.  When drug companies make this impossible by suppressing test results, not only do they violate their fundamental obligation of honesty with the public, their customers and their regulator, but they also break the bargain they have struck in return for the protection of their intellectual capital."  (Former NY Attorney General Eliot Spitzer<a href="http://www.slate.com/id/2260470/"> in Slate</a>.)<br /><br />Instead, as I have written before, maybe we ought to consider whether those with vested interests in drugs or devices ought to be running clinical research meant to evaluate their own products.<br /><br /> Ironically, while this discussion of how the Avandia spin cycle first began to revolve were going on, others were still trying to add revolutions (per minute).  In particular, a Reuters <a href="http://www.reuters.com/article/idUSN1511649320100715">story</a> noted:<br /><blockquote>Three influential groups of doctors who treat diabetes urged patients not to stop taking Avandia, saying on Thursday that while news about the controversial drug may be frightening, it would be worse to suddenly stop taking it.</blockquote><br />That is odd, given that Avandia has never been shown to improve clinical outcomes for patients with diabetes, and that there are many other drugs that control blood sugar which appear to be safer. But wait, there is more,<br /><blockquote>The Endocrine Society, American Diabetes Association and the American Association of Clinical Endocrinologists <em>worried that patients may be afraid to take Avandia</em>.<br /><br />'Patients should continue taking all currently prescribed medications unless instructed otherwise by their health care provider,' Dr. Robert Vigersky of the Endocrine Society said in a statement.<br /><br />'Stopping diabetes medications can cause significant harm and result in higher levels of blood glucose that may cause severe short term health problems and could increase the risk of diabetes-related complications in the long term.'</blockquote><br />Would not it make more sense to advise patients still on Avandia to consult with their doctors urgently about possible alternatives?  Meanwhile, it does not seem irrational to be afraid of taking Avandia, given the increasing evidence about its harms, and increasing evidence that what we know about its harms may be an under-estimate.<br /><br />So I wondered why these august medical societies seemed so unaffected about the doubts about Avandia's safety, and about the evidence offered to support its use that the latest news ought to generate. It turns out that all three of the medical societies get financial support from, -- wait for it --, GlaxoSmithKline.<br /><br />The Endocrine Society lists GSK as one of its <a href="http://www.endo-society.org/industry/CLB_about.cfm">Corporate Liaison Board Members</a>. The American Diabetes Association lists GSK as one of its <a href="http://www.diabetes.org/donate/sponsor/our-corporate-supporters.html">Banting Circle Supporters</a>, that is, those that give at least $1,000,000 a year. The American Association of Clinical Endocrinologists lists GSK as a member of its <a href="http://www.aace.com/org/cap/capdirectory.php">Corporate AACE Partnership</a>. (I was not able to find out the total amount contributed by GSK to either the Endocrine Society or the AACE.)<br /><br />So once again, the loudest voices in support of the product come from those used to, and perhaps dependent on financial support from its manufacturer. As a physician, I have been particularly disappointed that our medical societies, whose missions are ostensibly to support our professional values, seem to act more and more like marketers for the companies whose contributions, rather than members' dues increasingly support them.<br /><br />The cycle keeps spinning.<br /><br />For further thoughts on the latest in the Avandia case, see <a href="http://brodyhooked.blogspot.com/2010/07/side-trip-into-diabetes-selling-wrong.html">this post</a> by Howard Brody on the Hooked: Ethics, Medicine and Pharma blog, and <a href="http://alison-bass.blogspot.com/2010/07/when-will-big-pharma-learn-story-of.html">this</a> by Alison Bass on the Alison Bass Blog.

The Avandia Spin Cycle Continues Even After the FDA Safety Hearings

We have posted multiple times about Avandia (rosiglitazone), GlaxoSmithKline's star-crossed glucose-lowering drug.  While Avandia has re...

Đọc thêm »