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Wednesday, May 23, 20071179907741

A "Large" to "Very Large" Effect Size

Those who have been reading tdaxp over the past few months will know why this story is personal.

My first reaction is that the 43% higher risk of heart attacks

Pooled results of dozens of studies on nearly 28,000 people revealed a 43 percent higher risk of heart attack for those taking Avandia compared to people taking other diabetes drugs or no diabetes medication, according to the analysis published online Monday. The study, published by the New England Journal of Medicine, also found a trend toward more heart-related deaths.


Presumably means that .30 of the variation in heart attacks is explained by taking Avandia. This is a "large effect size." It should show up in smaller sized studies. Unless the most recent study is an outlier, it's strange that the effect has not been seen before.

Among worst cases, the increased risk is 64% (presumably, .38 of the variation is explained by taking Avandia). And indeed, apparently the FDA has known about this since 2002:

In 2002, U.S. Food and Drug Administration staff scientists called for reports of congestive heart failure to be included on the label of Avandia as well as Actos, made by Takeda Pharmaceutical Co. Ltd., the group said, citing an internal FDA document.

The group released the memo one day after researchers reported Avandia, or rosiglitazone, raises the risk of cardiovascular-related death by 64 percent and the risk of heart attack by 43 percent.


To me, though, blaming the FDA is like blaming the traffic police for a hit-and-run.

Glaxo strongly objected to the results and defended use of the drug, which treats type 2 diabetes.


I imagine I'll be following this for a while.

03:09 Posted in Health Care | Permalink | Comments (6) | Tags: avandia, glaxo

Comments

"To me, though, blaming the FDA is like blaming the traffic police for a hit-and-run."

So imagine if the traffic police thought of hit-and-run offenders as their clients.

http://content.nejm.org/cgi/content/full/356/17/1697

Posted by: a517dogg | Wednesday, May 23, 2007

a517d0gg,

It's hard for me to take this:

"One FDA scientist who was often criticized for being too concerned about drug-risk data was told by his supervisor to remember that the agency's client was the pharmaceutical industry. "That's odd," he replied. "I thought our clients were the people of the United States.""

seriously. The same snarky criticism can be directed at any client-centric approach ("That's odd. I thought McDonalds' clients were the shareholders.")

Likewise, the use-fees seem reasonable, though I'm hardly worked up one way or another.

More broadly, I'm for the legalization of marijuana and ecstasy, so it's hard for me to cry for the criminalization of Avandia.

What confuses me is how this large of an effect size -- this huge increase in heart attacks and deaths -- was not found earlier. The NEJM article's apparently a metareview, so perhaps it was. This weird secrecy bothers me, and I imagine more news will come of it.

Posted by: Dan tdaxp | Thursday, May 24, 2007

Basically the FDA was told to get drugs on the market faster and cheaper. They did, at the cost of less safety.

About a year ago I got a call from my doctor saying "Hey so you're on these two different (common) medicines. We just found out that the two separately are OK, but together they quickly cause an aggressive lymphoma so you should stop medicine A." In my view that's the kind of stuff that should be figured out by the FDA earlier, not after I've been on the medicines together for 4 years.

"What confuses me is how this large of an effect size -- this huge increase in heart attacks and deaths -- was not found earlier."

In the NEJM article they did say that there isn't enough money in follow-up research, that they just focus the money on getting drugs to market and then they ignore those drugs to focus on new drugs.

Posted by: a517dogg | Thursday, May 24, 2007

There have always been problems that show up later.

A few years ago I stunned a disbelieving internist when I refused to take a new drug called Vioxx. He tried to assure me it was fully tested and harmless. I insisted I preferred good old-fashioned pain to being a lab rat.

My dad is 88. He still cusses that gawd darned tylenol.

Just me, the FDA worked a lot better under Carter.

Posted by: sonofsamphm1c | Thursday, May 24, 2007

a517dogg,

The benefits-now/costs-later trade-off is a hard one. With increased medical tourism, I imagine that people will increasingly make it for themselves. FDA labels of quality (perhaps modeled after the color-coded terror alert system) may be the wave of the future.

sonofsamphm1c,

What was special about Carter's FDA? (I'm too young to remember myself).

PS: A new study on Avandia is out:

http://tdaxp.blogspirit.com/archive/2007/06/06/avandia-has-a-moderate-to-very-large-practical-effect-on-hea.html

Posted by: Dan tdaxp | Wednesday, June 06, 2007

It was slower because they deliberated a little longer before leaping into black water.

Posted by: sonofsamphm1c | Wednesday, June 06, 2007

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