Another example of how science works

Believers in “alternative” medicine tend to rely on testimonials, word-of-mouth, and charismatic woo-pushers for their information. Real medical science is much more difficult—and elegant. One of the most important types of paper that can be published is the “negative study”…

A “negative study” is one that did not support the supposition of the authors (or in “stat-speak”, the null hypothesis was not refuted). A study in the most recent edition of the New England Journal of Medicine is such an example.

There were many problems with this study from the start, not the least of which was one of the premises. One of the large drug companies wished to retain the patent on a successful medication. This isn’t easy to do. One way drug companies can do this is by creating a “combination” drug. For example, the company that sold Zocor (simvastatin) created a combination of simvastatin and another cholesterol medicine called Zetia. When simvastatin went generic, they were able sell it as a branded combination drug. This strategy likely saved them millions of dollars.

Lipitor, a competitor of generic simvastatin, is quickly losing market-share, and will eventually lose its patent. The company that makes Lipitor came up with an idea—a drug under investigation for raising HDL (“good” cholesterol) levels could perhaps be combined with Lipitor, taking the sting out of the generic medication crunch…and here is where the real controversy starts.

The large study released in NEJM put Lipitor head-to-head with a combination of Lipitor plus the new drug–there was no other control group. A proper study would have have had an arm with the new drug alone. The study was otherwise well-designed, and this bizarre research design seems to have resulted from the desire to market a new, more profitable drug. The medical community was concerned by such an overt intrusion of marketing into research.

But here the sinister machinations end. The study was a flop. In early statistics, increased mortality was observed in the group receiving the new drug, and the study was halted. There was no cover up, no attempt to “fudge” the numbers, just a wise decision to shut down the study and report the results. In “altie” circles, treatments are never abandoned because of failures—there is always some excuse to keep selling. Thankfully, in “mainstream” medicine, the system usually works—if a drug is not proven to be helpful, it is not used.

Unfortunately, because of the flawed study design, it will be hard to figure out if the new drug was responsible for this increase in mortality–after all, no patients received the new drug alone. It is commendable that the researchers did the right thing. Hopefully, they will use their data and their knowledge to see if this otherwise-promising new class of drugs may be beneficial to some patients. Meanwhile, unlike, say, homeopathy, no one will be selling it.

References

Philip J. Barter, M.D., Ph.D., Mark Caulfield, M.D., M.B., B.S., Mats Eriksson, M.D., Ph.D., Scott M. Grundy, M.D., Ph.D., John J.P. Kastelein, M.D., Ph.D., Michel Komajda, M.D., Jose Lopez-Sendon, M.D., Ph.D., Lori Mosca, M.D., M.P.H., Ph.D., Jean-Claude Tardif, M.D., David D. Waters, M.D., Charles L. Shear, Dr.P.H., James H. Revkin, M.D., Kevin A. Buhr, Ph.D., Marian R. Fisher, Ph.D., Alan R. Tall, M.B., B.S., Bryan Brewer, M.D., Ph.D., for the ILLUMINATE Investigators. Effects of Torcetrapib in Patients at High Risk for Coronary Events. Published at www.nejm.org November 5, 2007 (10.1056/NEJMoa0706628)