Phil Brewer thought he knew exactly what to do when the ambulance crew wheeled a well-dressed man in his late sixties into the emergency department. What he didn’t know: He was about to be involved in a series of events that would kill his patient. Brewer, then an assistant professor of emergency medicine at Yale School of Medicine, had been alerted by the crew that the man, Sanders Tenant (a pseudonym), had suddenly begun to talk gibberish while dining out with his family. Then his right arm and leg had gone weak.
Brewer suspected an acute stroke, but first he had to rule out conditions that can masquerade as a stroke, such as low blood sugar, a seizure, a brain tumor, and migraine headache. He had only minutes to make the correct diagnosis. Then the gathering medical team would decide whether to use a new stroke treatment that had recently been approved, a clot-buster known as tPA. Brewer called in a neurologist and the stroke team. After a CAT scan of the patient’s brain showed no sign of bleeding (something that would prevent the use of a clot-buster), the decision was made: Yes, use tPA. Despite following each step of the established protocol for this new treatment, Brewer experienced the unthinkable—his patient’s death. Tenant suffered a massive brain hemorrhage and died, not from his stroke but from effects of tPA, the drug that was meant to save him.
When we go to the doctor, we assume that the drugs he or she prescribes have been carefully tested to make sure they are both safe and effective. Most times they are. Yet sometimes the drugs cause more problems than they solve. Adverse drug reactions kill tens of thousands of people annually; one widely cited study published in the Journal of the American Medical Association (JAMA) in 1998 puts the number at more than 100,000. Recently a series of drug recalls have pulled back the curtain to show how the media, the public, and some doctors can misinterpret medical studies or take them out of context in ways that make medical treatments look safer and more effective than they actually are.
To a greater degree than ever before, powerful forces in the marketplace are impacting the quality, use, and safety of prescription medications. Drug manufacturers are spending more to promote their products while being subjected to tighter regulation and greater pressure for financial returns. The media are talking up each new “miracle cure” in headlines and television segments. Doctors have to navigate a tangle of administrative and medical concerns, one physician noting that “if you have a patient in your office, you can’t say, ‘Oh, I’m going to look at the drug company’s online database about Zyprexa.’ Most doctors don’t even know the databases exist. But even if they did, the next thing you know, three or four hours have gone by and you’ve missed all the patients waiting to see you.” Insurance companies and even the stock market play a role too. And consumers, increasingly subject to pharmaceutical advertising, are routinely urged to demand the best and the newest for their health. All together, this is a perfect storm for prescription drug problems.
How often do today’s medical “breakthroughs” become tomorrow’s discredited science? John P. A. Ioannidis, an epidemiologist at Tufts University School of Medicine in Boston and the University of Ioannina School of Medicine in Greece, studied the question. He examined the most-cited clinical studies published in the top three medical journals between 1990 and 2000 to see how well researchers’ initial claims held up against subsequent research. His findings, published in JAMA, show that the key claims of nearly one-third (14 out of 49) of the original research studies he examined were either false or exaggerated. Small study size, design flaws, publication bias (failure to publish negative results or duplication of positive results), drug-industry influence, and the play of chance were among the problems Ioannidis found that caused false or exaggerated claims.
Studies can be designed and interpreted in ways that make even ineffective drugs seem like lifesavers, says Curt Furberg, a well-known cardiovascular epidemiologist and former chief of the clinical trials branch at the National Heart, Lung, and Blood Institute in Bethesda, Maryland. Furberg, a tall, square-faced man with a Swedish accent, wants more objectivity in medical research. “We need more publicly funded studies,” he says, adding that manufacturer-sponsored research tends to minimize risks and exaggerate benefits.
A score of studies support his opinion. Among them is a 2003 analysis by Cary P. Gross, an associate professor of medicine at Yale School of Medicine, that was published in JAMA. In his survey, one study found that industry-sponsored research was positive 87 percent of the time compared with 65 percent positive for research that was not industry sponsored. According to Gross, the evidence was overwhelming that “industry sponsorship was likely to yield pro-industry results.” A 2006 analysis published in the American Journal of Psychiatry found that 90 percent of manufacturer-sponsored studies of antipsychotic drugs led to claims that the study drug was as good as, or superior to, every other drug in its class. Shannon Brownlee, an award-winning medical writer based in Washington, D.C., ascribed this to the “Lake Wobegon effect,” which renders every drug “above average.”
Furberg’s efforts to debunk overly enthusiastic interpretations of medical studies have led to occasional clashes with his colleagues. In 2004 the U.S. Food and Drug Administration (FDA) was preparing to hold hearings on the safety of painkillers known as COX-2 inhibitors, including Vioxx, which David Graham, an official in the FDA’s Office of Drug Safety, said may have caused an estimated 39,000 to 60,000 heart-attack deaths in just five years. At the time, Furberg was a member of the FDA Advisory Committee on Drug Safety and Risk Management. But after he told The New York Times that the COX-2 inhibitor Bextra also caused heart attacks, the agency made a surprising move: It removed Furberg from the advisory panel. Sandra Kweder, acting director of the Office of New Drugs, Center for Drug Evaluation and Research at the FDA, told a reporter that Furberg’s comments showed he could not be objective. Furberg now asks, “If bias was a concern, why did they allow 10 advisory members with ties to the manufacturers to be seated?” He was reinstated to the panel two days later and vindicated when the FDA announced that it had asked Pfizer to voluntarily withdraw Bextra from the market.
