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Medical science has always benefited from a healthy debate about the risks and benefits of various treatments. Doctors and other health professionals are trained to think critically about published data and to be cautious about recommending new (and old) treatments that have not met the highest standards of safety and efficacy.

Then, they leave the relatively protected environment of their training institutions and enter the real world of high pressure, big business that is medicine today. Squeezed by time pressures, struggles over reimbursement, marketers pushing their products, and patients demanding stuff they see on TV, they start to prescribe products and recommend treatments that they may not have under different circumstances. I’ve been there myself…writing a prescription for an antibiotic for a cold because I didn’t have the time or energy to argue the point with a patient whose mind was firmly made up.

But that type of pressure is minor compared to what is going on in the high stakes world of big pharma. To wit, the sad tale of Avandia, a diabetes drug with the scientific name of rosiglitazone; GlaxoSmithKline, its manufacturer; the FDA; and a medical researcher at the University of North Carolina (UNC), John Buse, MD, Ph.D, soon to be president of medicine and science for the American Diabetes Association.

John Buse, MD, Ph.D, a UNC researcher, reported that he was threatened by the manufacturer of Avandia, SmithKline Beecham, which later combined with GlaxoWellcome to become GlaxoSmithKline or GSK. According to a report on NCBI, Dr. Buse testified that after he raised concerns about Avandia’s heart risks, “it was mentioned on two occasions that there were some in the company who felt that ‘my actions were scurrilous enough to attempt to hold me liable for a loss in market capitalization.’

The report goes on to say that rather than pursuing his concerns, Buse offered to help the company with further studies and signed a clarifying statement drafted by SKB which was to be used with the investment community.” The NY Times reports that Dr. Buse sent a letter to the FDA a few months later, in March 2000, stating that “Avandia might raise patients’ risks of heart attacks, and he criticized the company’s marketing, saying it employed ‘blatant selective manipulation of data’ to overstate the drug’s benefits and understate its risks.” Oh, oh, this is not good news for a publicly traded company earning billions on the sale of this product.

According to another news report in The News&Observer (the article is no longer available), the then chairman of Dr. Buse’s department at UNC also pressured him “out of respect for a longstanding academic colleague“, who held a senior position in the company. This pharmaceutical company apparently left no stone unturned when it came to pressuring Dr. Buse.

Glaxo recently issued a statement saying, “We regret if, at any time, Dr. Buse felt the conduct of any employee was contrary to the spirit of open, scientific debate.” Well, I don’t know about Dr. Buse, but I think threatening an academic physician with being held liable for billion-dollar losses IS contrary to the spirit of open, scientific debate.

The bullying tactics surrounding this drug don’t stop there. They also involve the FDA, the government agency that is supposed to protect us from unsafe drugs. According to The NY Times, an FDA supervisor, Rosemary Johann-Liang, has said, “she was rebuked last year after calling for a stronger warning label on Avandia and a competing drug, Actos [by Takeda Pharmaceutical Co.’s” for swelling that could lead to heart failure. She went on to say that “she was ordered to retract her approval of the warning, lost her power to approve such assessments.” On June 6, 2007, under scrutiny by Henry Waxman and the Oversight Committee, the FDA announced that it would require a black box warning about the risk of heart failure on the labels of both Avandia and Actos.

And, if all of that is not enough, Dr. Steve Nissen, chairman of Cardiovascular Medicine at the Cleveland Clinic and author of a recent study, published in the May 21, 2007 New England Journal of Medicine, found that Avandia increased the risk of heart attacks by 43%. How did the FDA respond? According ABC News, Douglas Arbesfeld, a senior communications consultant to the FDA sent e-mails to journalists entitled, “What are St. Steven’s feet made of? Clay, perhaps?” The email included an anonymous blog accusing Nissen of playing favorites among drug companies. The blog posting, originally published in the Wall Street Journal, accuses Nissen of focusing his criticism on drug manufacturers that do not support drug trials at the Cleveland Clinic:

“Wake up pharmaceutical companies, this is a call from Dr. Nissen. If you don’t hire the Cleveland Clinic for your big trials, then you face the firing squad from Nissen and Company. The Cleveland Clinic was one of the most respected names in medicine, now they are positioning themselves as candidates to take over for a new series on HBO to replace the Soprano’s—the Clinico’s ‘next week who should we wack…’—Bata bing bata boon. Comment by Brian A – May 22, 2007 at 10:15 pm.”

Hmmmm. Who do you suppose wrote that blog…some interested, but impartial citizen or could it, just possibly, have been written by someone with industry ties*?

Dr. Nissen responded by telling ABC News, “I’m a pretty tough guy, but I’ll tell you, having this kind of an e-mail that questions my motives, broadcast to the major journalists with whom I work and have established a reputation is—it’s an outrage.”

Yes, Dr. Nissen, you are right, it is an outrage. The FDA is supposed to be protecting the company from unsafe drugs, not wreaking havoc on the reputations of researchers who raise legitimate questions about a drug’s side effects. And Henry Waxman, you are right, too, to be shining a light on a governmental agency that seems to have abdicated its responsibility to protect patients in favor of a stance that appears to protect drug company profits.

Clinical trials must be performed and the results disseminated without coercion and intimidation—can anyone really argue with that? And, drug companies must be held accountable for completion of high-quality post-marketing studies. Drug labels need to err on the side of caution so that doctors and their patients can fairly judge the risk-benefit equation for every medicine prescribed and taken.

The pharmaceutical industry has contributed greatly to the overall health of the world. They have also been rewarded handsomely for their products. It is way past time to rebalance the whole pharma/pharma oversight system and move away from a strong “need to sell” and toward an industry-wide “need to be safe” stance.


*(PS: While you are on the WSJ link, check out the obnoxious comment about Dr. Nissen written by someone who describes himself as “detail man”—as in “drug detail man”? Here’s a sample of what he says: “Nissen is a world-class boor, with an ego the size of an asteroid and a bug in his bonnet to screw the drug companies.” Civilized discussion, no?