“It goes on because there is a financial and regulatory reason that spurs it on,” says Sheldon Krimsky, an adjunct professor at the Tufts School of Medicine. As Krimsky points out, industry research has found that as much as 40 percent of all prescriptions in the US are written for off-label uses, despite the drug makers’ enforced silence. For some drugs, the figure is much higher. In 2003, doctors wrote $1.8 billion worth of off-label prescriptions — 90 percent of total retail sales — for a Pfizer drug called Neurontin. The drug was later the subject of a massive lawsuit here in Boston, alleging that Pfizer, in effect, paid off doctors to write off-label Neurontin prescriptions. Pfizer lost the suit in 2004, paying $430 million in fines.
“How do you get all this off-label use of drugs?” asks Merrill Goozner, director of the Integrity in Science Project and author of The $800 Million Pill. His answer: by paying doctors to prescribe the drug under the guise of testing. “That’s a huge aspect of these seeding trials,” Goozner says.
The resulting articles get out to more physicians — and the general public.
Seattle-based Berlex Laboratories, a subsidiary of Schering AG, paid for a study that ran in the May 26, 2005, issue of the New England Journal of Medicine, which concluded that its leukemia drug Leukine “decreased disease severity and improved the quality of life in patients with active Crohn’s disease.” The lead author, Joshua Korzenik of Harvard Medical School and Massachusetts General Hospital, is not only a paid consultant for Berlex and a member of its speakers bureau, but he also co-owns the patent behind the drug.
Korzenik says that he went to great lengths to “create a firewall” to protect the integrity of that study, which he and a colleague initiated when he was at Washington University, in St. Louis. The university established two committees to review the study results and process, and it even sent the compiled data to the outside clinicians who oversaw the bulk of the trials for individual review. Since receiving the patent, Korzenik has removed himself from further involvement in any research or promotion of the product.
Korzenik’s precautions are unusual, but the situation is not. And now, on the basis of his article, Berlex is doing just what Goozner described: spreading the word to physicians by sponsoring a huge, multi-site clinical trial of Leukine on Crohn’s patients.
University for sale
Now that industry-sponsored research has become a predominant reality, a battle is under way for control of the process, the data, and the writing: the sponsoring companies want to keep as much control as possible, and many academic researchers, or their administrators, don’t trust them with it.
For the past several years, the pendulum of power has been swinging toward the corporations sponsoring the research, particularly in conducting clinical trials. Their sponsoring contracts have frequently put the corporation in control of the design and oversight of the trials — which often take place at several or even dozens of sites. In some cases the sponsor also maintains drafting or final approval of the article, and even control over which data is sent to the academic researcher, and which isn’t.