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Clinical Trials And What to Do With Them

Allow me to get a little defensive. If I understand some of the critics of my industry, we spend most of our time making “me-too” ripoff drugs rather than doing something that provides any clinical benefit to patients. And, if I have this right, here’s how we determine efficacy: we run clinical studies until we get the answer we want, and then we bury all the other ones. (Mind you, we bury the data by giving it to the FDA, but stay with me here.)
OK, now let’s try to explain this. Merck has just released a study on its statin drug, Zocor. Following in the footsteps of two other studies with Pfizer’s statin, the market-leading Lipitor, Merck dosed patients who had just suffered heart attacks. Lipitor treatment seemed to show a real benefit in these situations, lowering the rate of later cardiovascular trouble, and Merck was hoping for (and no doubt expecting) the same thing.
But they were rudely surprised. At the lower doses of Zocor, they failed to show any benefit at all. And at the highest dose, while they managed to show a lower rate of second heart attacks, they still didn’t reach significance versus the placebo group. Worst of all, several of the high-doses patients showed the muscle-weakening condition rhabdomyolosis. That’s the bane of statin drugs, and the reason why Bayer pulled their compound (Baycol) from the market. (Just to complicate things, one of Merck’s placebo patients showed rhabdomyolosis, too, which is food for thought and should give you an idea of how much fun it is to interpret clinical trial data.)
So what’s going on here? Zocor and Lipitor both work by inhibiting HMG-CoA reductase. They hit the same mechanism. Were the patients different? The study’s authors say it’s possible. The patients in the Lipitor studies seem to have been receiving more aggressive therapy in addition to the drug. Are the drugs different? That’s possible, too. Lipitor, as it turns out, seems to lower the inflammation marker C-reactive protein much more than Zocor, and that could potentially make a difference.
But if the drugs are really different, what happens to the idea that Lipitor is just a me-too, yet another statin piling on the profits? If we in the industry hadn’t kept banging away at these drugs, we wouldn’t have ever known that better ones could be found. Would we? As I’ve pointed out in the past, if you’re going to market a drug in a category where the competition is ahead of you, you’d better have some improvement to point at or set about finding one. Lipitor came into the market under the banner of “lower dose / higher efficacy”, and it may be picking up more advantages as time goes on.
Now, if we believe that the drugs aren’t different, which will be an interesting thing to try to prove at this point, then we have to figure out how much weight to put on this study. How does it go into the Great Clinical Trial Repository? With an asterisk? Then shouldn’t the earlier two studies with Lipitor have one, too? This is the same situation I spoke of before.
And what about this clinical trial data in general? Isn’t this the sort of bad news that we’re supposed to be sweeping under the rug over here? A full article in JAMA complete with vigorous editorial commentary. . .some rug. Oh, and one other thing: those two earlier Lipitor studies that showed a benefit. One of them was from Pfizer(/Pharmacia), as you’d expect. But the other one was from their competition. Bristol-Meyers Squibb has been trying to prove that their statin, Pravachor, is better than Lipitor, and failing. Where’s that damn rug when you need it?

5 comments on “Clinical Trials And What to Do With Them”

  1. fin2ut says:

    What’s to apologize for? ‘Me-too’ drugs are a good thing. Practically by definition, such drugs are developed for extremely common diseases. So what do we as a society want? One lipid pill? One ulcer pill? Anyone who takes that kind of logic seriously is misguided, at best (which is a gentle way of calling them idiots). The Not-Idiots, however, realize that the argument is facile, but use it to cynically further their short-term interests, & this is really the key point. We have the moral authority here, not our detractors, so we should attack their motives, not vice-versa. Moreover, we should attack their short-sightedness & global inadequacy in interpreting medical data.

  2. Mike Levy says:

    Derek, here’s an idea for a blog entry:
    Over the last 15 years, how many drugs have been FDA-approved that are truly irreplacable and life-saving, that save 1000 or more lives a year, which couldn’t (or wouldn’t) be saved in any other way. How many drugs that fit that category are approved per year?
    As a layman, the drugs that come to mind are Gleevec, Taxol, the various AIDS drugs…
    — Mike

  3. Doug Sundseth says:

    Let us, for the sake of argument, assume the counter-factual, “All me-too drugs are the same as their competitors.” Will the price of a drug without competition be higher or lower than the price of a drug for the same condition that has three competitors?
    Given the assumed ease with which entirely new drugs can be produced (just look at the press), it would only make economic sense to exclusively make unique drugs with higher profit margins.
    By the available evidence, it would seem that drug companies are only interested in altruistically reducing the price of treatment at the expense of their profits.

  4. Derek Lowe says:

    Doug: There’s not as much competition on price in the drug industry as you’d expect, mainly because the drugs inside a given category aren’t as equivalent as critics make them out to be. If Lipitor really is more effective, for example, then Pfizer has more pricing power.
    I’ll have some more to say on the me-too issue in the next post, if I have time tonight to write it.

  5. Doug Sundseth says:

    Sorry, that was sort of my point. If all similar drugs are equivalent, new drugs will compete on price and drive prices down. If similar drugs are not equivalent, new drugs will treat some part of the population more efficiently than they were previously being treated (presumably this is a good thing). In either case, the argument against me-too drugs has serious problems.

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