April 3, 2008

Vytorin



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.

 







Comments

Let me see if I can sum my ... (Below threshold)

April 5, 2008 2:27 PM | Posted by Anonymous: | Reply

Let me see if I can sum my perspective of your entry in a couple of sentences. Study is conducted between competing drugs. Study finds what previous studies have found, though expecting to find significant differences of the thickening of artery walls (plaque build-up), but differences remain insignificant. Your point is that this study was unnecessary due to a fault in the set up of the experiment, “these are familial hypercholesterolemia patients who have already been on statins for decades-- this effect won't be present in them.” And, therefore doctors fail to notice why their experiment was faulted when motivated by market forces to produce desired results  "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."  Doctors are narcissist because they, like everyone else, are instruments of economic (grants for med school) and social (preservation of identity) forces.

Instead of the above argument consider how doctors focus on long-term by examining the doctor-patient relationship? There are really only three reasons anyone goes to a medical (implied to exclude psychiatrists) doctor: something is wrong, a check-up, or pregnancy. When something is wrong with a patient, the patient demands relief (treatment of the symptoms) as fast as possible, a good computer or doctor would be able to consider all possible options at once, assuming the doctor has a core-quatro processor. But again, most doctors (I think you’ve written about this before) fall back to heuristics to treat the patient: the established patterns in medicine (be they faulted or correct) to treat most patients. Unfortunately, a million things could always go wrong, so how do you treat that? You ask as many questions about the patient’s history or recent activity to gage the probability that the patient might have syphilis or the flu. With most people as patients, their responses will conceal pertinent information, purposefully or accidental. And here’s where I put the narcissism on the patients instead of the doctors. At this point, there is enough information out there to get an idea of what you as a patient might be infected with or suffer from such that when setting up a “something’s wrong” appointment, the patient should be prepared to carry a productive conversation about his or her own health. At this point, the narcissism might fall back to the doctor as the doctor tries to narrow the actual causes vs. symptoms from the annoying know it all patient. Obviously, as you’ve pointed out before, a doctor thinking of symptoms only is probably the narcissist and the doctor thinking about causes is the actual doctor. I’m sure most doctors are a mix of both.

On to doctor’s thinking long-term, how can they think long-term? Doctor’s have no control over how a patient abuses his or her body. All they can do is provide preventative information, which can be boiled down to avoiding addictions, eating right, and exercising regularly. By the time a patient is on statins, the long-term mentality for the doctor and the patient is gone, well except that the patient will be on static long-term and occasionally watch what he or she eats. I understand that some people need statins, but I consider the situation analogous to anti-depressants: how many people really need to be on drugs? (Of course, with restless leg syndrome, it seems as though everyone will get a chance, thank you pharma-propaganda) Long-term is self-help for the patient, short term is treatment by the doctor. Taking a complete different direction, the removal of asymmetric information from the doctor-patient relationship (improving communication between patients and doctors, pharmacies and doctors, and doctors and doctors, and every other possible interactive identity and doctors) will vastly improve treatment, assuming doctors can be trained to identify causes rather than just symptoms. Cue the Google health concept and issues of patient privacy.

Response to final paragraph: At what point do people stop thinking of the bigger picture and default into the daily routine? When they become narcissists?

Vote up Vote down Report this comment Score: 0 (0 votes cast)
between the two of you, her... (Below threshold)

April 6, 2008 7:42 AM | Posted by trei: | Reply

between the two of you, here's what I fear we're up against: total brake-down.

I don't trust the doctors anymore. they don't know anything; plus, they don't care. too many problems, so little time, too little do we know about a few of them, and all of it is biased by economics and/or politics. now what?

do I lay down and die? do I google it and self-medicate? do I google it and discuss differential diagnosis with my doctor? do I eat well, exercise and hope for the best? do I go back to school and become a doctor myself just to make sure that at least my family will be alright?

oh, wait. if I don't trust doctors, I'm paranoid. If I think I can only trust myself, I'm a narcissist.

Now what?

Vote up Vote down Report this comment Score: 0 (0 votes cast)
I'm trained to this regard ... (Below threshold)

April 6, 2008 10:49 AM | Posted by KWL: | Reply

I'm trained to this regard so it's no surprise that I always consider what the "system" is that is in play whenever I read material discussing scenarios that affect people and populations. I've come to believe that at least two frames of reference are always in tension when considering what impacts our lives and how. These are the large and the small, the large typically concerns itself with treating humankind as a large mass, so almost always an "efficiency" problem; the greatest coverage and what single practice will reach the farthest with the most good possible to the mass.

The small is, of course, the treatment of humankind as individuals. And here, surprisingly we often see "efficiency" as a problem as well, though not the same as the former, here it is more to do with making the best possible treatment of each individual and how to apply this practice to as large a population as possible. The best practices of each still fall short of the ideal.

My point, finally, is that understanding problems of this regard are, in fact, critically important. As our sophistication as social citizens evolves, and interestingly pressured by increasing population, the next great political evolution will need to be integrating into the global society to the point of inherent practice how to navigate well the line between treatment of the individual in antagonism of the masses and vice-versa.

Vote up Vote down Report this comment Score: 0 (0 votes cast)

Post a Comment


Live Comment Preview

October 30, 2014 08:13 AM | Posted by Anonymous: