More fallout from yesterday’s big news about Avandia and its association with heart attacks and cardiovascular death.
“The 43% increase in heart attacks/myocardial infarctions and the 64% increase in death from cardiovascular causes is also sensational. It is the same statistical trick the pharma companies use to promote the efficacy of their products, and the same eye-catching method the Women’s Health Initiative reported when hormone replacement therapy was discouraged. But if you look at the actual numbers they seem less impressive and less news-worthy, but still significant.”
“FDA’s analyses of all available data are ongoing. FDA has not confirmed the clinical significance of the reported increased risk in the context of other studies. Pending questions include whether the other approved treatment from the same class of drugs, pioglitazone, has less, the same or greater risks. Furthermore, there is inherent risk associated with switching patients with diabetes from one treatment to another even in the absence of specific risks associated with particular treatments. For these reasons, FDA is not asking GlaxoSmithKline, the drug’s sponsor, to take any specific action at this time. FDA is providing this emerging information to prescribers so that they, and their patients, can make individualized treatment decisions.”
“For the record, I was never a big fan of Avandia, especially since I saw a small study in a 2003 issue of the Mayo Clinic Proceedings which showed that ‘thiazolidinediones can cause or exacerbate heart failure and pulmonary edema and should be avoided in patients with left ventricular dysfunction or chronic renal insufficiency.'”
“Is there an explanation for these apparently disparate effects? It may lie in the fact that while rosiglitazone is a pure PPAR gamma agonist pioglitazone is a mixed PPAR gamma and PPAR alpha agonist. PPAR alpha agonism may confer more favorable lipid effects on pioglitazone. Specifically, while both drugs raise HDLC, pioglitazone has little or no effect on LDLC while rosiglitazone raises LDLC. Pioglitazone seems to lower triglycerides more effectively than does rosiglitazone.”
“As long as the FDA approves the drug for use, public advertising cannot be suppressed. The issue and the consequences is reflected in today’s news about the heart attack risk with the popular diabetic drug Avandia. The long-term benefits and long-term risks are unknown at the time of FDA approval and there is no energetic but only casual attempts to obtain information regarding the long-term benefits and risks after the drug is released to the general public.”
“Take a page out of Pfizer’s book: Keep Avandia on the market and hire the best cardiologist there is — actually it will have to be the second best; the cardiologist who dissed Avandia in the NEJM (Dr. Nissen of the Cleveland Clinic) is considered one of the best, if not best — to start a massive study of the cardiovascular effects of Avandia (with the goal of proving that it has no adverse CV effects, of course). Some people thought Pfizer was crazy when it followed this strategy for Celebrex, but that product has survived, albeit a little beaten up.”
“On May 1, he and Ms. Wolski sent the New England Journal of Medicine a manuscript tying Avandia to a statistically significant heart risk.
Glaxo learned of the submission and dispatched four executives to Cleveland. Dr. Krall argued that the data didn’t clearly show a risk. Glaxo said yesterday that the meta-analysis technique isn’t the most rigorous way to reach conclusions about safety issues because it combines studies that are designed differently and the data collected in the studies may not be comparable.
Dr. Nissen said the meeting was ‘very collegial and respectful,’ but the Glaxo team didn’t change his mind about the safety concerns.”
Merrill Goozner (via Schwitzer):
“Once again, millions of Americans have been subjected to unwarranted risks from a drug that had no real benefits over other, cheaper drugs already on the market. And now that they’re on this more expensive drug, they face additional risk if they decide to get off because of what they just learned. Thanks a lot, FDA.”
“But the FDA does not have to worry about sales or share prices. Its job is supposed to be to protect the public’s health and safety. Why didn’t it act?
Has its funding by users’ fees made FDA officials feel they are responsible first to the drug, device, and biotechnology companies that pay these fees?
Has its dependence on advisory panels often populated by people who have financial arrangements with drug, device and biotechnology companies made it more used to these companies’ interests than any others?
We can hope that the Avandia story will mark the tipping point on the way to reinvigorated FDA that sees itself as responsible first and foremost to the public, not specific commercial interests.”