Avandia Should Stay On Market: FDA Panel
11 CommentsBy Ed Silverman // July 30th, 2007 // 6:31 pm
After a widely anticipated, day-long meeting, the FDA advisory committee voted 22-to-1 that Glaxo’s diabetes med should remain available because the benefits outweigh the risks. But the panel also found that Avandia increases the likelihood of heart attacks and should carry new safety warnings.
The panel, which also discussed the possibility of a patient registry, voted 20 to 3 that the studies presented during the daylong panel meeting showed Avandia carried a higher risk of “cardiac ischemic risk.” The FDA often follows the advice of its advisory panels, although the agency isn’t required to do so.
“It’s probably beneficial to some people,” FDA panel chairman Clifford Rosen, a senior staff scientist at the Maine Center for Osteoporosis, told Bloomberg News after the meeting. “You can keep the highest-risk patients from taking the drug.”
“My feeling here is that we’re being asked to take a very draconian action based on studies that are very inadequate for us to make that kind of decision,†Rebecca Killion, a patient representative and committee member from Bowie, Md., told The New York Times. Gerald Van Belle, a committee member from the University of Washington, told the paper that “when this particular drug is used, there must be some care taken in who gets it.â€
Earlier in the day, David Graham, the infamous FDA medical reviewer, called for Avandia’s withdrawal and estimated it caused up to 205,000 heart attacks, strokes and death from 1999 to 2006. For every month that Avandia is sold, he argued, another 1,600 to 2,200 patients are likely to suffer heart attacks or strokes, some of them fatal.
Yet even as Graham and his boss, Gerald Dal Pan, who oversees the FDA’s safety office, openly supported yanking Avandia, another FDA official publicly disagreed. Bob Meyer, who directs the FDA office that reviews new diabetes drugs, said he remained undecided and acknowledged a “fundamental disagreement” took place among agency staffers.
Avandia was the world’s best-selling diabetes drug last year, with sales of $3.3 billion, but usage plummeted after a New England Journal of Medicine report on May 21 linked the medicine to a 43 percent increased risk of heart attacks, setting off an industrywide controversy that prompted a debate over the value of the meta-analysis and a congressional hearing.
Dr. Remulac
I love it when I get to say a hearty and tongue-in-cheek “Told ya so!”
GC
Wonder what the cost of each vote was…..
Duxiangjun
The question is how can the FDA overlook each person’s right to life, liberty and the pursuit of happiness? Several drugs have recently been recallled due to various errors. These “errors” are lives cost.
This has to stop! I honestly believe that each physician should have to tell his/her patient individually about each drug. By doing so, it makes not only the patient aware but also the doctor.
Ed
Hey Dr. Remulac…How long have you worked for GSK?
This finding is a joke. I wonder how many more people have to die/suffer before the FDA does something?
Melody
Looks like another case of CYA. Doctors (those who have “arrangements” with GSK) can re-state FDA’s decision and inform patients, “Of course Avandia’s safe; the FDA said so.” Eventually, defense attorneys will use the same argument as they face some prosecutors who feel that murder is murder, no matter what agency endorses the weapon.
Dr. Remulac
I’m way too ethical to have ever worked for GSK! The FDA can only act on the strength and totality of the data available to it, and despite the incredible lengths that GSK, the FDA, and others have taken to slice and dice the Avandia data, at best all anyone can see is that the verdict remains inconclusive. Where they had better quality data, such as in patients on insulin, they acted with appropriate warnings. What the layworld needs to do is leave statisitics and medical decision making to the experts, and stop swallowing sensationalistic media crap hook-line-and sinker. All the metaanalyses and other retrospective analyses do is develop associations and form hypotheses. It is a well know statistical fact that with a large enough sample, any 2 factors can be associated with each other. Here’s a great example (humor intended): Analyzing data from the entire world population over the past 200 years, I have found that there is an association of 1.00 between breathing air and mortality - meaning that 100% of people who dies breathed air before doing so. Should the FDA ban breathing the air?? I make that outlandish point to provide an example of the dangers of over-interpreting retrospective or pooled data. While I agree that there does appear to be a signal associating Avandia use with a statistical risk of MI, it has yet to be borne-out in prospective controlled trials - which is the gold standard for making those determinations. The definitve answer will come when RECORD (flawed design), ACCORD, and BARI-2D are completed over the next few years.
Dr. Remulac
In the meantime, patients with type 2 diabetes and their prescribers have tough decisions to make. Sulfonylureas and metformin have been well-studied, and so far metformin seems to be the best bet. The jury is still out on Actos, and anyone who thinks that there is adequate evidence to use Actos instead of Avandia is a fool. We’ll know more when the same analyses that were done for Avandia are completed for Actos. Newer drugs like Byetta and Januvia - who knows??? They haven’t been around long enough in order to make a call.
Remember, these drugs are approved and prescribed in order to control glucose and to keep HbA1c values as low as possible. If you’re a diabetic patient with an HbA1c of 8.2% (elevated) and you’re already on the combination of metformin/sulfonylurea, what do you do next? This is where the art or medicine enters, and where prescribers and their patients work together to decide next steps based on available data. There’s very good data that adding Avandia/Actos will help achieve better HbA1c control, but now there is a some evidence that this could increase CV risk (absolute risk goes up by only a fraction of a percent), so you have to take that under consideration. Instead of going mad over this whole Avandia debate, the general public should be demanding better prevention of CV disease!! There are a multitude of papers showing that patients with diabetes are not being well-served when it comes to controlling other CV risk factors, such as high LDL-C, low HDL-C, high TG, high blood pressure, etc. What this debate should be about is why this is not happening. I can guarantee you that if all patients on Avandia were also being adequately treated so as to achieve full control of their lipids, blood pressure, etc, you would find absolutely NO increased risk of CV events. That’s what we should be focusing on in our society.
Melody
Dr. Remulac, You state: “What the layworld needs to do is leave statisitics and medical decision making to the experts.” Exactly WHICH experts are we to trust? The pro-pharma experts . . . or the anti-pharma experts . . . or the unbiased researchers–if and when such creatures can be discovered? I know . . . we should trust the FDA, or perhaps the many doctors who receive their post-med school education from pharma PR, conflicted “prestigious” journal articles and/or Ken/Barbie pharma reps.
You also state: “The definitve answer will come when RECORD (flawed design), ACCORD, and BARI-2D are completed over the next few years.” The definitive answers won’t matter to those who die in the meantime, especially if the answers confirm today’s theories.
Dr. Remulac
Melody - despite what you may think, there are many competent, ethical, and caring scientists remaining in clinical practice, academia, pharma (yes, even there!), and federal agencies. I know it may seem that is not the case based on all that you may read, but I’d caution you to “walk a mile” in someone elses’s shoes before you claim to be an expert on that basis. Is our system imperfect? Yes. Is it hopeless and completely morally and professionally bankrupt as you describe? No.
Your last statement is flatly insulting, and way off the mark. Science is about testing hypotheses and proving causality to a degree not explained by simple chance alone. What science tells us at this point is that there is no way to actually know if your supposition is correct, so your accusation that people are being unduly harmed is unfounded. You have to balance KNOWN benefits against KNOWN risks. In this case, you are using risks that cannot be said to be known by a scientific standard.
Is there a chance (statistically speaking) that Avandia may indeed increase the risk ov MI?? Yes, there is a chance, but the actual increase is so small that even with data from hundreds of thousands of patients exposed for 6-months to several years, the picture still is not clear. From a clinicians point of view, this is acceptable risk. Here’s a case in point that you may grasp: Aspirin has saved countless lives over the decades by preventing MI or improving outcomes during/after MI. However, over these decades many thousands of patients have been hospitalized or died secondary to GI ulceration/bleeding, and this number is far more than have ever been harmed to date or will be harmed by Avandia. Should we blame unethical scientists, pharma, the government, etc for all of this? Should we immediately ban the use of aspirin? No - you have to understand the full risk/benefit profile in order to make that decision, just as is being done with Avandia now.
Hank
As far as risk, the Advisory Committe confirmed Nissen’s estimate. So the “experts” have spoken on that one by an overwhelming majority.
The issue then becomes risk/benefit, as Dr. R. rightly says. Benefit is not an equation - it comes down to weighing other tx options, other risks, seriousness of condition (diabetes is serious), whether those who can most benefit with least risk can be identified, whether there may be ways to reduce risk (like adding aspirin), etc., etc..
Some of the experts - Graham most definitively - argued for withdrawal. His calls in that regard have turned out to accurately predict eventual FDA action some 80% of the time. So a “betting man” would predict that is Avandia’s eventual fate.
In any event, the aspirin analogy doesn’t help much exactly because of the complexity of risk/benefit assessment. You can’t take any one dimension (e.g., number of hospitalizations) and make that the sole criterion (unless, I suppose, we were talking trainloads).
Personally, I am not an expert and so I have no basis beyond a modicum of confidence in those whose views, over time, have most often won the day.
Dr. Remulac
Well-stated. Thank you for your comments.