Map of life expectancy at birth from Global Education Project.

Monday, May 21, 2007

Here we go again . . .

You don't need me to tell you about the news that Avandia (generic name rosiglitazone), a drug widely prescribed for Type 2 diabetes, has been found to be associated with an increased risk of heart attacks and associated deaths. This is definitely bad news, because one of the major reasons why you don't want to get Type 2 diabetes, and presumably want to control it once you do get it, is because diabetes is associated with an increased risk of heart attacks and death from heart disease.

So, the value added I can give you here, that you probably won't get from your nightly news or your local fish wrapper, is that it points to a fundamental flaw in the FDA drug approval process. This drug, like other drugs for Type 2 diabetes, was approved based on mostly fairly short-term trials (a year or less) that showed that it reduced blood sugar, and that in turn largely based on a marker called glycolated hemoglobin that responds to blood glucose levels over time. Doctors and patients who are trying to manage diabetes generally measure their success based on glycated hemoglobin levels.

This is what we call a "surrogate marker." The real reason you would want to take a drug for Type 2 diabetes is because you want to avoid the complications of diabetes, including death. But the drug approval process isn't based on any evidence that the drug actually does that. It's based entirely on this surrogate end point. While it seemed a reasonable assumption that better glucose control would mean less heart attacks and longer life, it appears not to be true after all.

The study is a so-called meta-analysis, that is it is based on data available from studies that have already been done, none of them with the actual purpose of demonstrating the cardiac benefits or harms of rosiglitazone, so it's not as revealing as we would like. Actually, this means that chances are the stuff is even more dangerous than the investigators were able to determine. But I'll let them speak for themselves:

These emerging findings raise an important question about the appropriateness of the current regulatory pathways for the development of drugs to treat diabetes. The FDA considers demonstration of a sustained reduction in blood glucose levels with an acceptable safety profile adequate for approval of antidiabetic agents. However, the ultimate value of antidiabetic therapy is the reduction of the complications of diabetes, not improvement in a laboratory measure of glycemic control. Although reductions in blood glucose levels have been shown to reliably reduce microvascular complications of diabetes, the effect on macrovascular complications has proved to be unpredictable. After the failure of muraglitazar [a drug that failed to win approval due to demonstrated cardiac risk] and the apparent increase in adverse cardiovascular outcomes with rosiglitazone, the use of blood glucose measurements as a surrogate end point in regulatory approval must be carefully reexamined.

I'll spell it out one more time: Disasters like this one would be much less likely to happen if we had an FDA that worked for us, not for the drug companies. And we won't get that until we have a president who works for us, which we do not have. Enough!

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