Given all the scandals surrounding the pharmaceutical industry, you might expect academic researchers to maintain a certain skepticism that drug companies might manipulate data or bury bad results or misrepresent findings. Instead, it sometimes seems they’re the only ones left who trust big pharma. A national survey conducted by the Harvard School of Public Health found many clinical-trial investigators “willing to accept provisions that give industry sponsors considerable control.” For that reason there is growing concern at Boston’s universities, teaching hospitals, and medical-journal publishers, where some fear that a few highly publicized disasters — bad research with a well-known institution’s name on it — will turn a Harvard, Tufts, or Massachusetts General into just another untrustworthy name, tarnishing all the good work along with the bad.

Off label = big money
Not so long ago, almost all clinical medical trials were set in motion when an academic researcher decided to pursue a scientific hypothesis. Today, many of them originate when a company wants to sell a device or drug. This is partly because full-scale pharmaceutical testing in today’s expanding market has become enormously expensive, and the industry has surged ahead of government support for research and development. As a result, as much as 80 percent of all clinical trials are now paid for by private industry. “Any clinical trial won’t be done unless somebody stands to gain from it — let’s face it,” says Douglas Gregory, CEO of Cardiovascular Clinical Studies, Inc., in Boston.

Often, the drug company then finds an academic to accept a research grant to serve as lead author of the resulting article — and frequently as its paid “opinion leader,” who may receive honoraria for talking up the product through the company’s “speaker’s bureau,” at continuing medical-education courses, and elsewhere. Harvard, Tufts, Boston University, and other local medical schools and teaching hospitals are filled with professors receiving such honoraria; the Integrity in Science Project Web site (cspinet.org/integrity/index.html) has a searchable database of them. “The more prestigious the institution, the more likely the industry associations,” says John Abramson, clinical instructor at Harvard Medical School and author of Overdosed America. “The drug companies understand who the key opinion leaders are.”

The changing nature of research so concerned the editors of more than a dozen top medical journals — including the New England Journal of Medicine, the Journal of the American Medical Association, and Annals of Internal Medicine — that in September 2001, they wrote in a group letter that, until recently, “academic, independent clinical investigators were key players in design, patient recruitment, and data interpretation in clinical trials.... This may be a thing of the past.” As a result, they announced a new policy that required those seeking publication to disclose exactly who performed what duties on the research and authoring of each submitted paper.

But those disclosures rarely make it into the news articles, Internet forums, and doctor small talk that help increase the number of prescriptions written, boosting sales. In particular, clinical-trial results with an academic institution’s name on it do something that a drug company legally cannot: promote “off-label” use of a drug, or prescription for maladies for which it has not received FDA approval.

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Yahoo.com’s Healthwise encyclopedia tells us, for instance, that Ortho Tri-Cyclen, along with other birth-control pills, “are commonly used” to treat dysfunctional uterine bleeding. The only clinical study of Ortho Tri-Cyclen’s application for that purpose — finding it to be “an effective use” — came in 2000 from Ann Davis of Beth Israel Deaconess Medical Center. Not only was Beth Israel paid by the manufacturer, Ortho-McNeill (a Johnson & Johnson subsidiary), to host the study, but Davis was also a consultant for Ortho-McNeill and a member of its speakers bureau. Not only that, but all four of her co-authors on the Healthwise article were Ortho-McNeill employees. (Davis, now at NEMC, did not return calls from the Phoenix.)

Davis is not the only medical specialist whose name and institution have fronted research — co-authored by the very same four Ortho-McNeill workers — suggesting off-label uses for Ortho Tri-Cyclen. One or more of those Ortho-McNeill employees appear as co-authors on journal articles by Mass General’s Steven Grinspoon, reporting that Ortho Tri-Cyclen may improve bone density; from the University of Pittsburgh, on the use of Ortho Tri-Cyclen to restore hair growth; from Scott & White Memorial Hospital, in Temple, Texas, on the use of Ortho Tri-Cyclen for menstrual-cycle control; and from the Center for Health Studies, in Beechwood, Ohio, and the University of Palermo, in Italy, on the use of Ortho Tri-Cyclen to treat acne.

“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.