Another clinical trial finding that a branded drug is no better than a generic. No one should be surprised, no one is surprised, but the popular posture is to pretend that you were the only one who wasn't surprised and to claim vindication.
That's the posture adopted by the attendees at the American College of Cardiology through their proxy, Inquisitor Harlan Krumholz, who said "You've just seen a negative trial that should change practice, especially the way we in this country have prescribed" the drugs. His prior contribution to medicine was an article about how Canada is better than America. I wonder if Dr. Krumholz would have been so outspoken if the results had found it was better?
But of course, his anger isn't about the ENHANCE study, it's about the role of Pharma.
In truth, the ENHANCE study was devoid of any useful conclusions. Vytorin wasn't worse, certainly-- it was better on a number of really important metrics, but failed to be better (read: was the same) in one metric (intima diameter) which itself isn't a useful one; it is a proxy for a proxy for the ultimate question of morbidity and mortality.
But for something with minimal significance it generated lots of emotion, and lots of internet time. I don't know the official definition offhand, but that's a pretty good one for pornography.
Pornography serves no productive pupose, but it allows for a vigourous act of involuted posturing. It is always for masturbation; even when couples use it, it still ends up promoting a kind of mutual masturbation. You're there; your mind isn't. I'm not judging it as evil or useless, but let's be clear it doesn't advance the species. It's just self stroking. It always seems like a good idea at first, charged with emotion and expectancy, and a feeling of necessity- you need to do this. It sounds great if it's 1:36am and you're both drunk and caffeinated in a Courtyard Marriott in Jefferson City; but... but afterwards you have a vague, empty feeling-- "what was the point of that? Should I have just rented The Empire Strikes Back?"
Pornography looks at the obvious, it reveals what is already known but (un)dresses it pseudo-novel settings to entice, titillate. It's no suprise to anyone that the penis goes in the vagina, but you want to see it anyway. And so ENHANCE-- and what a great name-- "Let's look at the intima! Let's get close ups! Wow!!"
The problem isn't with clinical trials in theory; it is with the obsession medicine has with conducting them, no matter what, for any reason, at any cost, and in the process creating new subtypes of "patients" and "disorders" that don't actually exist. "Dementia related psychosis" or "depression secondary to a medical condition." And meaningless outcome measures: Clinical Global Improvement; intima thickening.
Porn again: there's a fetish for everyone. Some docs get off on intima thickening, I guess, so there will be studies to satisfy, though the benefit to the patient is far from obvious. I'm not saying there's no value in a study comparing, for example, all antipsychotics for efficacy in a convoluted paradigm only a fetishist would understand or care about; I'm simply saying there isn't $60M in value there. If you're actually paying for porn, well, you're an addict.
Yet another adjunct study; yet another "open label phase"; yet another "me too" drug; yet another cosmetic indication-- we're not expanding our knowledge base, we are creating froth, we are masturbating. It's no surprise that residents-- people young enough to prefer actually having sex to masturbation-- find more pleasure reading straight science or straight theory than they do from a clinical trial. As you get older you slow down, I guess, and suddenly a crossover design seems like a good idea.
Why so many clinical trials? Don't blame Pharma, who would undoubtedly be much happier with just an indication and a salesforce. There the blame falls squarely on academics. Discovery is rarely the goal; productivity is. Cover the salary, buy out some of the clinical time; and of course create a name for yourself in the hierarchy. You've made it when you can say something like, "oh, Bill Collins's group over at Yale is studying that, he's a really great guy." It's narcissism, not in a malignant way, but in an entirely easy, natural, self-fulfilling way that can be justified to oneself as not hurting anyone. Hey, it doesn't mean you don't love your wife, or that you don't care about patients. But you've been Associate for two years, and...
And how do you cover a salary? Ask Pharma for money-- and be damn sure to carefully design your study for the outcome you want. I don't have reliable data on this, but I'd bet that most people looking for porn on the internet don't type "naked ladies" into the search bar and hit return. You want results.
There is a downside to masturbation, of course, the most significant being the potential to interfere with your desire to have sex with your actual spouse. So it is with academic clinical trials. Do any patients benefit from the ejaculate in the Journal of Clinical Psychiatry? Do the sticky pages of the New England Journal hold any promise for patients? And did those studies prevent-- by time, money, or energy-- the study something else more valuable? The answer is yes, a thousand times yes. I'm sure ENHANCE seemed like a good idea at the time. Now, not so much. I think it's great that the AHA has taken the unusual step of denouncing the use of Vytorin as a first line agent on the basis of one single, flawed, study with apparently no serious attention to its findings. What have they accomplished? Nothing, except to solidify the role of pornography as legitimate science.
Academia is a regression to adolescence. You're not trying to achieve a goal, you want to make progress towards the goal. "Someday, I'll..." That's it. that's everything. Adolescents aren't confident in the goal, they're not sure they really want it or it's worth it. But there will be all sorts of drama around it. That's academia. They're not really scientists, their semioticians, not after knowledge but constructs, frameworks. "Science requires time and diligence-- can't jump to conclusions." Sure. Not like what happened with ENHANCE.
I had expected all this from psychiatrists; it's comforting, but simultaneously horrifying, to know that it exists in the same strength in cariologists as well.
I am anonymous, but I am not without character, and I will put my money where mouth is. As of the open Tuesday, I'm in for 500 shares of Schering-Plough, not because I believe in the company, or in Vytorin, but because I know capriciousness when I see it. After everyone cleans up, SGP will bounce back.
Thanks, ACC. You just made me 20%.