Wednesday, January 16, 2008

A bad day for pharma

Last week I came across an interesting article published in Public Library of Science Medicine, an open-access, peer-reviewed medical journal that has produced some excellent literature since its inception. The article evaluated market information and came to the conclusion that big pharmaceutical companies spend roughly twice as much on marketing as they do on research and development. This came as no surprise to me given that of 1147 new patented products released on the Canadian market between 1990 and 2003, only 12% of them could be considered to be novel drug products. The rest are essentially "me too" drugs which are efforts by drug companies to grab a chunk of a large market or to prevent an emerging generic product from eroding market share. So it stands to reason that if they spend so little on research and development that the drug companies would start to get a little sloppy.

The New York Times recently reported some naughty business by Merck and Schering-Plough, makers of Zocor and Zetia (Ezetrol in Canada). The two pharma behemoths, with combined annual revenues of $33 billion, co-market Vytorin, a combination of Zocor and Zetia. You've seen the commercials: some of your cholesterol comes from your diet, which Zetia blocks, and some comes from Grandpa Joe, which Zocor blocks (not Grandpa Joe, the cholesterol). They spent more than $200 million advertising this new drug and planned on sharing the profits.

However, they had a hard time justifying the combination given that there was little evidence for any benefit over existing therapies. So they started the ENHANCE trial. This trial attempted to show that Vytorin would reduce arterial plaque buildup better than Zocor alone. (I will reserve comment for later on the fallacy of this approach, given that this does not necessarily prove that the drug reduces heart attack or stroke risk.) A short time ago, the results were due to be released. Let us just say the companies were not very forthcoming with information.

Finally the powers that be forced the companies to release the information after multiple rounds of stalling. Turns out they had a good reason to not have the data go public. While Vytorin reduced cholesterol better than Zocor alone, turns out it actually caused plaques to buildup in the arteries more, almost twice as fast as Zocor alone. Vytorin patients were also more likely to DIE and suffer HEART COMPLICATIONS, although I must stress this was not statistically significant so may be due to chance alone. That's called a negative result. Drug companies don't like to publish negative results.

In an incredible article published in the New England Journal of Medicine, study authors looked at FDA-registered studies for 12 antidepressants including over 12 000 patients. Of the 74 studies looked at, 31% were not published. It was shown that whether or not the studies were published was related to whether or not the outcomes were positive, which means that subsequent clinical decisions made on the basis of published research were biased completely toward the positive. Only 1 of the 38 positive studies was not published. Of 36 negative studies, only 3 were published.

The really interesting part comes when they compare the effect size shown for these antidepressants in the published studies versus all the studies, published or not. The effect size of the published data was on average 30% higher than the effect sizes reported in all the data, thereby grossly inflating the efficacy of these agents to those accessing medical literature, namely healthcare professionals relying on it to make informed decisions in treating their patients. In other words, according to published data, 94% of the trials conducted on these 12 agents had positive outcomes. In fact, only 51% had such outcomes.

So to the group of guilty parties that includes Merck and Schering-Plough, you can now add GlaxoSmithKline, Forest, Eli Lilly, Organon, Bristol-Myers Squibb, Pfizer, and Wyeth.

That begs the question: if even I as a healthcare professional cannot necessarily trust what I read in peer-reviewed academic medical journals, how can you, the average consumer trust what you read in the lay press?

Verbosen verboten

Prevaricate: to stray from or evade the truth

1 comment:

Anonymous said...

I must say, the word of the day is very fitting to the post.
Well done.