It’s been amusing to watch former Pfizer executive John LaMattina try to pick apart Ben Goldacre’s new book, Bad Pharma, a powerful indictment of the industry in which LaMattina used to work. This is not the occasion to get into the details of this battle, but as an aside let me just say that I would advise any representatives of the pharmaceutical industry to think very carefully before choosing to take on Goldacre.
What I want to focus on here is an assertion, accepted by both Goldacre and LaMattina, that is simply mistaken. LaMattina’s latest post is a response to a brief statement by Goldacre in his book that there has never been a head-to-head clinical trial comparing statins. Both writers accept this statement as a fact.
I think it is very curious that neither Goldacre not LaMattina remember the PROVE-IT TIMI 22 trial published in NEJM in 2004. This trial compared pravastatin (Pravachol, Bristol Myers Squibb) with atorvastatin (Lipitor, Pfizer). I’m particularly surprised that LaMattina doesn’t remember it because it turned out to be a huge, unexpected boon for his company, despite the fact that it was sponsored by a rival.
I won’t get into all the complex medical and scientific issues here, but the history is fascinating: At the time Pfizer’s Lipitor was dominating the rapidly growing, astonishingly lucrative statin marketplace, despite the complete absence of any trials with hard clinical outcomes. Its success was based entirely on atorvastatin’s extremely potent LDL lowering properties.
Pravastatin, by contrast, had been tested and shown to benefit patients in several important outcome trials, but it was well known that it did not lower LDL as effectively as atorvastatin. Bristol Myers maintained that the outcome trials should outweigh the surrogate endpoint, and to prove the point funded the TIMI group to run the pugnaciously-named PROVE-IT trial.
From a business perspective, PROVE-IT turned out to be a huge, self-inflicted disaster. Instead of demonstrating, as BMS intended and hoped, that pravastatin was as good as atorvastatin, the trial ended up showing that atorvastatin was superior to pravastatin. Fueled by the boost from PROVE IT, Lipitor surged to new heights and became the best-selling drug of all time, while Pravachol became a much less successful also-ran. (See this chart.) In retrospect, BMS took a gamble and lost big time.
I’m not sure how the true story of these drugs and the PROVE IT trial fits into either Goldacre’s or Lamattina’s narrative about the pharmaceutical industry. But Goldacre’s larger point, which he was attempting to make when he mistakenly said that comparative trials with statins had never been performed, strikes me as being impossible to refute. Goldacre writes with passion and eloquence about the need for large, simple trials to compare therapies, and this far more important point strikes me as unassailable.
I think the way the PROVE IT story relates to this issue is that we shouldn’t expect industry to perform these hugely necessary trials on its own. Industry learned an important lesson from PROVE IT and now most pharma companies are extremely reluctant to perform these sort of risky comparative studies. In his book Goldacre suggests several innovative ways large and important trials could be performed without significant extra expense. Maybe it’s time now to start acting on these ideas.
Saturday, March 02, 2013
Bad Pharma And The Statin Wars - Forbes