In 2004 GlaxoSmithKline became the first major drug manufacturer to publicly disclose all the data from clinical studies of its products, including information that is usually treated as a trade secret. It was responding to a lawsuit by Eliot Spitzer, then New York’s attorney general and now its governor, who accused Glaxo of hiding data about the safety and efficacy of one of its drugs. Sure enough, the company had concealed data indicating its antidepressant Paxil increased the risk of adolescent suicide. More-recent research suggests that link might not exist after all, but even if that proves true, it doesn’t excuse the initial concealment.
A month later, Merck pulled its new pain reliever, Vioxx, off the market after clinical trial data showed that patients taking it had a 400 percent greater chance of heart attack than those taking the comparison drug, naproxen. Merck researchers implausibly argued that the difference was due not to damage caused by Vioxx but to the other drug’s cardio-protective properties. No previous research had found that naproxen protects the heart.
For critics of the pharmaceutical industry, the Vioxx and Paxil incidents are evidence that conflicts of interest have thoroughly corrupted American medical research. “The Vioxx withdrawal serves as a reminder of the dangerous potential for conflict of interest that exists when pharmaceutical and other for-profit businesses control the dissemination of findings generated by medical research,” warned a November 2004 editorial in the Dayton Daily News. In March 2005, the left-leaning Center for Science in the Public Interest (CSPI) pointed out that a Food and Drug Administration (FDA) panel that reviewed data on the risks posed by COX-2 painkillers like Vioxx included 10 researchers with financial ties to the companies that manufactured those drugs. Had the panelists with conflicts been excluded, a majority of the remaining members would have voted against approving Vioxx for distribution.
The Paxil incident prompted a June 2004 statement from the New York Attorney General’s Office warning that “the ability of drug companies to pick and choose the research they provide doctors in support of their product is an outrageous conflict of interest and puts us all in harm’s way.” An August 2005 story about industry-funded medical research in the San Jose Mercury News quoted Sheldon Krimsky, a longtime critic of pharmaceutical companies, who asserted that “the entire system of drug testing is filled with conflicts of interest.”
There’s no question that some companies have behaved badly in some cases. But are these cases typical or rare?
Activists, politicians, and other critics claim conflicts of interest are pervasive in pharmaceutical research. Several years ago CSPI established an Integrity in Science Project to investigate and publicize the destructive influence of industry-sponsored science. Not to be outdone, the Union of Concerned Scientists launched its own Scientific Integrity Program to “push for reforms that will protect our health, safety, and environment.”
Politicians are jumping on the bandwagon, proposing more-stringent regulations of private clinical research. Sens. Christopher Dodd (D-Conn.) and Edward Kennedy (D-Mass.) recently introduced the Fair Access to Clinical Trials Act, which would require all clinical trials to be registered in a central government database. Marcia Angell, a senior lecturer in social medicine at Harvard University, wants to ban privately funded clinical trials altogether. Instead, she proposes that drug companies be forced to pay into a government fund that would finance a new National Institute of Prescription Drug Trials to conduct all future clinical testing.
Supporters of such changes argue that conflicts of interest undermine public trust in and support for scientific research, endanger research subjects and patients, and boost medical costs by encouraging physicians and patients to use new treatments that are no better than cheaper alternatives. Yet public trust in biomedical research remains high, and that trust seems to be justified. Subjects in clinical trials hardly ever suffer serious harm, and instances in which dangerous side effects turn up after drugs are approved are relatively rare. Rather than making medicine unnecessarily expensive, pharmaceutical innovation ultimately reduces health care costs, because new drugs usually have advantages that pay off in lower medical bills.
The critics’ concerns are not entirely groundless. Driven by self-interest, drug companies and researchers do occasionally hide data or run drug trials that produce data of scant clinical value. But private initiatives by medical journals, universities, and companies are already addressing these challenges, making government action unnecessary.
In 2005 The Journal of the American Medical Association reported that 5.6 percent of health spending in the U.S. goes to biomedical research, more than in any other country. In nominal dollars, funding for biomedical research in this country rose from $37 billion in 1994 to $94 billion in 2003. Even adjusted for inflation, that’s an increase of almost 100 percent. The National Institutes of Health provided 28 percent of that funding; industry gave 57 percent; state, local, foundation, and other federal agencies accounted for the remainder.
This cooperation between academia and industry has been essential to speeding new treatments from lab bench to hospital bedside. “By any measure, the interactions between academic research and industrial research and development, as epitomized by biotechnology, have been overwhelmingly positive,” wrote Thomas Stossel, a professor of medicine at Harvard and a co-director of the Hematology Division at Boston’s Brigham and Women’s Hospital, in a 2005 New England Journal of Medicine article. “We should celebrate their achievements and protect the process that led to them.”
But one man’s beneficial cooperation is another’s conflict of interest, a phrase that has acquired an inappropriately sinister connotation. As defined by the former Harvard epidemiologist Kenneth Rothman in a widely cited 1993 New England Journal of Medicine article, a conflict of interest is “any situation in which an individual with responsibility to others (which includes professional responsibilities) might be influenced, consciously or unconsciously, by financial and personal factors that involve self-interest.”
Such conflicts are not at all unusual. David Korn, senior vice president for biomedical and health sciences research at the Association of American Medical Colleges, noted in 2000 that “conflicts of interest and commitment are ubiquitous in academic life (and indeed, in all professional life), and conflicting pressures inherent in the academic milieu, e.g., for faculty advancement, obtaining sponsored research funding, winning the acclaim of one’s professional peers, competing for prestigious research prizes, and yes, desiring to alleviate human pain and suffering, all may be more powerful in influencing faculty behavior than the prospect of material enrichment.” Such conflicts do not in themselves imply wrongdoing, Korn stressed: “Since these conflicts can never be eradicated from professional life, their existence must be accepted and not equated with professional misconduct.”
Corrupt or Well-Informed?
To illustrate the dangers allegedly posed by conflicts of interest, industry critics repeatedly point to a handful of atypical cases featuring erroneous results, suppressed data, or harmful side effects. (See “Ties That Blind,” page 38.) In addition to such anecdotal evidence, they cite studies that show a correlation between industry funding and results that are favorable to the sponsors. As the researchers themselves acknowledge, however, there are benign explanations for such correlations.
In 1998 The New England Journal of Medicine published an article that claimed to show how commercial interests influenced the scientific evaluation of data on the relative safety and effectiveness of calcium-channel blockers, a class of drugs used to control high blood pressure. The study found that “authors who supported the use of calcium-channel antagonists were significantly more likely than neutral or critical authors to have financial relationships with manufacturers of calcium-channel antagonists (96 percent vs. 60 percent and 37 percent, respectively).” The authors concluded that this “strong association” meant the “medical profession needs to develop a more effective policy on conflict of interest.”