Now what?

Now what?

As Diabetic Investor predicted before the Avandia meeting even started, the panel voted in favor of leaving the drug on the market. Several panel members noted their vote to allow Avandia to remain on the market was not a vote of confidence for the drug rather a vote based on the data that was supposed to condemn the drug. Simply put the data was just not strong enough or perhaps clear enough to warrant a full withdrawal from the market.


In today’s Wall Street Journal, former FDA Commissioner David Kessler said the Avandia controversy “will chart the future direction of the agency on drug safety,” and result in more time and money spent by companies getting drugs approved, and “more safety for the consumer.” While Diabetic Investor agrees the drug approval process will take longer and result in higher costs to drug makers, we strongly disagree that there will be “more safety of the consumer.” If we have learned anything at all from this controversy it is difficult if not impossible to draw a straight line from using a particular drug to a single set or series of adverse events. Frankly if the issue was that clear cut, Avandia would have been removed from the market long ago.


We further disagree that this “will chart the future direction of the agency on drug safety” not unless the agency develops a crystal ball that can accurately predict the future. It is statements such as these that show just how out of touch the FDA has become with reality. Granted the FDA has to do their best to reassure the public that their doing their job and the drugs people take are safe and effective. Yet the public has become increasingly skeptical when the agency can’t reach agreement on Avandia. Keep in mind this issue has now been debated for over two years and we still do not have a clear answer on the central question; does Avandia lead to an increased incidence of adverse cardiovascular events.


As we noted yesterday there are no guarantees that after a drug has made it all the way through the lengthy drug approval process that a problem won’t develop after the drug has been on the market for several years. Like it or not this is the reality of situation.


While GlaxoSmithKline (NYSE:GSK) could claim victory here, it would be a hollow victory at best. Avandia sales have fallen dramatically here in the US and European regulators are also looking into the drug. With the majority of the lawsuits now settled this clears the way for Glaxo to voluntarily remove the drug from the market and put this issue behind where it belongs, in the past. A voluntary withdrawal would also help Glaxo repair their reputation with the FDA and as the company knows they will have other drugs before the agency which will receive extra scrutiny because of the way Glaxo handled Avandia. A voluntary withdrawal will take the FDA off the hook and allow the healing process to begin.


It also remains to be seen how this vote will impact the reputations of Dr. Nissen and Dr. Graham, two of Avandia’s strongest and most vocal opponents. It seems fairly obvious to Diabetic Investor that Dr. Nissen’s original meta-analysis which started this whole mess added to the confusion of the panel members; panel members who for the most rely on scientific evidence not retrospective analysis when making decisions. Diabetic Investor has never been a big fan of meta-analysis as there are too many variables in how the analysis is constructed to make it a useful tool. As one statistician noted the results of any meta-analysis can vary greatly depending on which data sets are used. And there are no hard and fast rules as to which data sets should or should not be included in a meta-analysis. Put more concisely a researcher can skew the results of the meta-analysis by which data they chose to use and which they chose to ignore.


One also to wonder what our distinguished Senators will have to say about this vote, Senators Grassley and Baucus who have it made it their missions to paint GSK as the Evil Empire hell bent on destroying the free world. For all their grandstanding the issue which they helped to create remains unsolved. This is another reason Diabetic Investor believes GSK will voluntarily pull Avandia off the market. The company correctly understands they not only have to repair their reputation with the FDA, but they want to be taken off the Senators hit list and move out of the public spotlight. The Senators may not have a clue when it comes to knowing much about drugs or drug development but they do have the power to make Glaxo’s life a living hell.


Diabetic Investor also believes yesterday’s vote really won’t change the minds of physicians who already have stopped prescribing Avandia and have already switched patients who were using the drug to alternative medications. As we have noted previously we can’t think of a single reason why any physician would risk using the drug given its tainted reputation and abundance of effective alternatives available.


For those who framed this issue as a major cataclysmic event for the FDA and the Obama administration, the panel’s vote only reinforced the need for major reform at the agency and did little to advance the possibility of reform. Diabetic Investor never help out much hope this panel meeting would do anything more than add to the confusion and as we correctly predicted there was no clear cut conclusion that would be gained from this debate. Given the strong positions staked out by both sides and the results of the vote the issue is not dead and will likely be debated well into the future. Anyone hoping this meeting would put an end to this whole mess allowing everyone to move on will be vastly disappointed. It’s just a matter of time before all the players involved whether they were pro or con will begin talking about why the panel failed the public.


So here we are two years into this controversy and still we have no clear answers. From the very beginning Diabetic Investor has looked at this issue form a very simple perspective; will anything good come from all this debate. Will patients be better off than before? Will the FDA develop better standards and methods for approving new diabetes drugs? Will the physicians who treat patients with diabetes have greater confidence in the drugs they prescribe? Will researchers develop a set of standards on how and when to use meta-analysis? Will the FDA get back to following their stated mission which states that decisions should be made using scientific evidence? Will everyone wake up and realize that no matter how hard drug companies try and how rigorous the approval process there is no such thing as a completely risk free drug? And lastly, will people realize that diabetes is a complex disease state which left uncontrolled leads to devastating and costly consequences?


Sadly the answer to these questions is a huge NO. About all that’s happened here is that the FDA has become overly conservative, the drug approval process has slowed to a crawl and no one is quite sure just what constitutes a reasonable risk/reward profile for drugs used to treat diabetes.


Just where we go from here is anyone’s guess or as we noted at the very beginning; Now what?