April 3, 2008


The article that has infuriated everyone, that no one will read.

If you don't know: Schering-Plough funded a study between its drug Vytorin-- a combo of Zocor and Zetia, vs. Zocor alone.

The results were expected: the combo Vytorin reduced cholesterols and other parameters better than Zocor alone.

The other results were not expected: the combo was no better than single Zocor in preventing artery thickening.

SP tried to delay the results of the trial: cue righteous indignation everywhere.

The lead investigator's now famous emails:

This starts smelling like extending the publication for no other [than] political reasons and I cannot live with that.

and later:

you will be seen as a company that tries to hide something and I will be perceived as being in bed with you!

SP should not be able to delay the results (BTW, they are almost never able to do so.)

But absolutely no one wants to ask the more pressing question: why did anyone do this study in the first place?

Pay attention, and you will see why medicine will collapse if it continues this way.

  1. There was already data that showed it lowered cholesterol better than statins alone-- and no one disputed that data.
  2. Doctors already have the cognitive bias that two drugs must be better than one (though may have more side effects.)
  3. Vytorin was already approved.  It wasn't looking for a new indication.  This would have been barely knew information even if it was positive:  "It reduced intima thickening?  Didn't we already kind of assume that?"

So the answer is, obviously: SP wanted new data to put in a shiny detail piece.  Gotcha.  But why would a team of doctors care to take on such a purposeless study? 

Do you understand?

And another question: why this outcome?  Why not the obvious one, reduction in mortality? 


Before that can be answered, you have to understand that this story isn't about Vytorin, it's about Pharma and their evil, lying ways.   Never mind that they didn't lie, that the drug did exactly what it was said to do.  It's the public's anti-Pharma backlash, acted out in emails and a cardiology conference.

For sure, they tried to delay the data's release.  But look through the stories, the hostility is really about SP pushing Vytorin, period.

"Vytorin doesn't work."  Wrong.  "Vytorin isn't better than Zocor alone."  Also false: it is better in several different ways (LDL, total cholesterol, CRP, etc.)  What it was the same for was intima thickening.   Could it be that that single parameter is flawed?

Both drugs slowed the progression of intima thickening.  To the same extent.  Here's the problem: both drugs work by slowing the progression and reducing the existing size.  In this study, the size was not reduced because the walls were already thin-- these are familial hypercholesterolemia patients who have already been on statins for decades-- this effect won't be present in them.


So if Vytorin is better than Zocor in several ways, but not for the outcome of intima thickening; and anyway that's hardly the outcome we want to know about-- why such a backlash?

And why would SP do this to itself?  Why not do a study on mortality-- much more probably with a better result-- instead of a technically different study of a proxy for a proxy for mortality?  (Intima thickening is measured because you can't see the tiny plaques themselves, so it is assumed that more thickening must mean more plaque, which must also mean more death.)

The answer is this: doctors don't care about mortality data.  No, don't run away, listen.  The game has never been about reducing mortality specifically-- otherwise a lot more people would be on lithium and a lot less on VPA-- or anything else, for that matter.  And we'd prescribe nicotine gum much more often than Prozac.  Etc.

The medicine game has always been about acute treatment, not chronic.  (Psychiatrists get away with a focus on maintenance because they make their patients come in every one or two months.)  Doctors don't focus on long term because of the perception that a million things could always go wrong, better to fix what's wrong now.  And worse, acute treatments simply default into chronic treatments.  Or a series of chronic acute treatments.

In short: for the first month of an illness, medicine is awesome.  After that, we pretty much don't have a clue what we're doing.


And the reason for that isn't SP or anyone else.  It's bias.  Doctors are a collective existing for a higher purpose; but each individual doctor is a person, and that person has to eat; and he has to eat where his peers will acknoweldge him, value him.  It's narcissism.  Not selfishness; they're not greedy or spiteful or envious.  They simply have an identity they need to validate; a career they need to promote, and by hell if intima thickening is going to get me a grant to pay for some of my academic salary, what's the harm?  

I sympathize, I do.  But the harm is that you've just pissed your life away on another treatment parameter that isn't necessary, while overall life expectancy-- flatlines.