Part of the difficulty in detecting drug side effects, Furberg says, has to do with study size. Drugs go through a regimen of tests prior to receiving approval from the FDA. During the first two stages, called Phase I and II trials, an experimental drug is tested on just a few hundred volunteers to look for side effects. If no serious problems are detected, the drug is tested for efficacy in a Phase III trial. But efficacy trials often involve only several hundred to a few thousand patients. And while a study of 200 to 300 arthritis patients is large enough to show whether a new drug relieves pain, just one such study isn’t large enough to pick up less-common—but potentially deadly—side effects. Furberg says, “If only one in a thousand patients will die from a heart attack, an efficacy study of 200 or even 2,000 patients is simply too small to get a reliable answer about rare side effects.” Seemingly rare side effects can take tens of thousands of lives when millions of prescriptions are written.
How do today’s medical “breakthroughs” become tomorrow’s discredited science
Such limitations in a study’s design can escape detection even by top peer reviewers and medical editors. Marcia Angell, the former editor-in-chief of The New England Journal of Medicine (NEJM), says that most doctors are ill equipped to critically assess the conclusions of researchers. A trim woman with a warm smile, Angell leans forward in her seat at her home in Cambridge, Massachusetts, and says, “Let me tell you the dirty secret of medical journals: It is very hard to find enough articles to publish. With a rejection rate of 90 percent for original research, we were hard pressed to find 10 percent that were worth publishing. So you end up publishing weak studies because there is so much bad work out there.” Doctors, Angell says, are not skeptical enough about what they read in top journals. “They should say, ‘I don’t believe this; prove it to me.’”
The rest of the media don’t get any better marks. Gary Schwitzer, director of graduate studies in health journalism at the University of Minnesota School of Journalism, examined 400 medical news stories that were carried by 57 of the top print and broadcast media. “The majority failed to adequately discuss costs, quantify harms and benefits, and examine the quality of the studies,” Schwitzer says. Many quoted a sole source and failed to report potential financial conflicts. Schwitzer concluded that media reports give “a kid-in-the-candy-store portrayal, where everything is made to look amazing, harmless, and without a price tag.” Patients themselves “should not escape notice as willing collaborators, wishing for magic potions and taking drug company money to support consumer organizations,” Schwitzer continues.
Phil Brewer, the doctor whose stroke patient died after being treated with tPA, says media portrayals of new medicines are often “irrationally exuberant.” He points to a May 2007 article in The New York Times that he says typifies the problem. The article, about stroke victims, said that the clot-buster “tPA was shown in 1996 to save lives.” Yet in 2001, the American Heart Association (AHA) had withdrawn the claim that the drug “saves lives” from its promotion of tPA for stroke after the group was challenged to provide scientific evidence to support that claim. The AHA was also the subject of scrutiny when it was revealed that in the decade prior to its recommendation that doctors use tPA for stroke victims, the heart association had received $11 million from Genentech, tPA’s manufacturer.
The same Times article quoted a number of doctors saying that too few stroke patients were receiving tPA, yet failed to mention that many of these same doctors had received funding from Genentech. Nor did the article give a hint of the ferocious battle among doctors about the safety and efficacy of tPA: While a number of professional associations endorsed the drug, many others, such as the American Academy of Emergency Medicine, said it should not be considered the standard of care for acute stroke.
Asked about this reporting, Barbara Strauch, health editor of The Times, responded, “While some researchers had said in interviews that they believed the drug saved lives, our article incorrectly stated that the study had made that conclusion.” Strauch said the paper would publish a correction—which it did this past April, nearly a year later. (This was done in response to DISCOVER’s inquiries.) She added, “It is also true that some researchers quoted in the article, like many stroke researchers and many who study other diseases, are funded by and receive honoraria from the pharmaceutical industry. However, the main sources for our article were researchers at the National Institute of Neurological Disorders and Stroke (NINDS), who, the National Institutes of Health says, do not take money from drug manufacturers.”
“What you read in the media are these stories of a stroke patient getting tPA and miraculously improving within minutes,” Brewer says. “But we’ve all seen that happen in the ER, even before tPA was ever invented.” After his patient died, Brewer, wary of drawing conclusions on the basis of a single case, wanted to make sense of the data about tPA. Even though a landmark 1995 study conducted by NINDS showed that 12 to 13 of every 100 treated patients had less disability, Brewer says that “it was hard to put the conflicting [study] results together and determine whether the benefits really did outweigh the risks.” So, like many physicians, he turned to the articles and analyses of Jerome Hoffman, a professor of medicine and emergency medicine at UCLA. “Dr. Hoffman has a brilliant mind,” Brewer says. “He is listened to and trusted by more emergency physicians than anyone I know.” An authority on medical studies, Hoffman, it turns out, was also the lone dissenting member of the AHA panel that recommended tPA for stroke.
