On June 6, 2007, a packed audience at a Congressional hearing listened as the U.S. Food and Drug Agency (FDA) announced that it was putting its most serious safety warning on the diabetes drugs Avandia (rosiglitazone) and Actos (pioglitazone). Just 23 days before, hardly anyone in the world thought there were any major problems with these two drugs. To understand how the way we look at these medications could change so quickly, let’s review what we’ve known for a long time, and what we have recently learned.
First, some key background facts. On May 21, 2007, The New England Journal of Medicine published an analysis of data from 42 separate studies, and concluded that Avandia was associated with an increased risk of heart attacks and death from heart disease. Because of limitations in the data available to the researchers, most experts considered their findings alarming, but not definitive proof that Avandia was harmful.
One June 5, The New England Journal of Medicine published a second study, which the manufacturer of Avandia touted as providing reassurance that its drug was safe. However, many experts looked at the data, and were not reassured. This study is intended to last six years, and the researchers were reporting on less than four years of follow-up because of the “crisis” caused by the May 21 study. This second study found “no evidence of any increase in death from either cardiovascular causes or all causes” but this is a preliminary analysis of study that is ongoing, the study’s authors described its findings as “insufficient” and “inconclusive.” In addition, researchers found trends suggesting that, with a longer period of follow-up, the group of patients assigned to take Avandia could have a higher rate of heart problems.
What do we know? And not know?
No one should start Avandia because they think it will lower their risk for heart disease. There are plenty of other medications for treating diabetes, several of which are older (and therefore we have more data on them) and much less expensive. In fact, it’s hard to make the case for any patient to start Avandia given the recently published data.
Should patients on Avandia stop it? This is more of a grey area. We are worried, but do not know for sure that this drug is bad for your heart. So, my colleagues and I are not calling up every patient on this drug and telling them to stop it as soon as possible. On the other hand, plenty of patients are calling us on their own, and telling us that they are worried by the news report. I am saying to them, “Let’s switch you to something else.”
Should Actos be tarred with the same brush as Avandia? Actos is in the same chemical class as Avandia, and there is some evidence that it might carry an increased risk for heart failure. But concern about Actos has not been nearly as great as the worries about Avandia. Some physicians are even switching patients from Avandia to Actos.
Avandia helps the insulin made by the pancreas work more effectively
What have we learned?
There has been a lot of finger-pointing in the days since – at the FDA for being too lax… at the manufacturer for over-promoting its drug … at doctors for being too quick to embrace a new drug with scant evidence of benefit. Who’s really to blame? I don’t think the FDA is “broken” or that pharmaceutical companies are evil. They both have very difficult jobs. Developing drugs is incredibly risky and detecting problems such as those that appear to be plaguing Avandia takes years of research and information on many thousands of patients taking the drug. And doctors do their best to make sound decisions based on the information at hand. But we're not psychics, and our recommendations should and do change in response to new information.
We want medical progress, and there will surely be many more drugs that make their debut in the decades ahead that help people enjoy healthier, longer lives. Some of them are sure to have problems that are not recognized for some time. Sure, the FDA can and should improve, but we should not assume that it can ever be perfect.
I actually think that the lesson of the Avandia story is the same as the lesson from the Vioxx story (a pain reliever that was pulled off the market after concerns about its impact on cardiovascular health): patients and physicians should take their time in embracing new drugs. Before you go on a new-to-the-market medication, let some time go by – time during which side effects and serious complications can emerge. In the meantime, see if your medical problems can be controlled with older, generic drugs. You will be safer, and have lower co-payments at the same time.
Thomas H. Lee, M.D., is an internist and cardiologist who is a Professor of Medicine at Harvard Medical School. He is also the Network President of Partners Healthcare System, the integrated delivery system founded by Brigham and Women's Hospital and Massachusetts General Hospital.
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Comments: 6
Thank you for your article.
Trying new drugs is a lot like upgrading to a new computer operating system (OS). As concerns the latter, computer experts generally recommend waiting until the first service pack is released before upgrading to a new OS. That way, the first round of bugs and glitches will be worked out before you install the OS on your system.
The same can be said for new drugs. During clinical trials, drugs are only tested on a limited number of patients, leaving us with little knowledge of the long-term effects on larger numbers of patients. Unless a patient has a terminal illness and has exhausted all known treatments, it is probably best to wait for more long-term data.
One of the problems with new drugs is direct to patient advertising. Patients see advertisements lauding the benefits of a new drug and then want to try it. In my opinion, physicians should advise patients about the risks of using drugs that are new to the market. If patients knew that older drugs were far less risky and could achieve a good result, they'd be more likely to choose a conservative course of treatment.