9 No. 4
Drugs and Money
Pharmaceutical companies, academic medicine, and the flow of funds and favors
Reviewing conflict-of-interest policies
Funds flowing in
"We accept money because we need to do clinical trials, and that's where the rubber meets the road in this conflict-of-interest business."
"I'm not under any illusion that [drug companies] give money for the sake of neuroscience. They won't do a study if the potential is there for the outcome to have a negative impact on marketing."
THE INTELLECTUAL COMMUNITY
Bringing the Big Questions to the Community
Re-imagining the Gustafson Seminar
Multiversity or University?
Pursuing competing goods simultaneously
On the failure of roots and the strength of weak ties
On the many occasions when Nassir Ghaemi has addressed his colleagues about psychiatric drugs, the audiences are invariably dubious, despite his credentials as a respected researcher. Theirs, however, is not a natural skepticism instilled by the scientific method, but one that emanates from the knowledge that Ghaemi’s presence before them came courtesy of a pharmaceutical company, which paid him to speak about one of their products.
“No matter what I said they would to some extent be skeptical because a drug company funded the venue,” says Ghaemi, an associate professor of psychiatry and public health and director of the bipolar disorder research program. “Even if I said that drug X was good for some uses, and then at the next talk said it was bad for other uses, they’d still be skeptical. It seems that there is no way I could convince people that I really believe what I tell them.”
Distrust of drug companies—and those hired to speak for them—is in vogue; the vast volumes of money flowing from the industry to academic medical centers have stirred up ethical eddies that trouble consumer groups, the media, a growing number of medical professionals, and even the recipients themselves. For the most part, institutions and researchers eagerly accept the cash. Researchers who don’t accept it run the risk of severing a huge source of financial support that can make or break careers. Ghaemi observes that, before they have established a track record, academic physicians have little choice but to rely on drug company funding to launch their professional trajectories. Competition for the primary alternative, National Institutes of Health grants, is fierce, and the resources not as plentiful. In 2003, the NIH—the largest source of public money for health research—handed out about $23 billion for research grants, training, and research and development contracts. The same year, member companies of the Pharmaceutical Research and Manufacturing Association spent $33 billion on research and development for new drugs, much of it awarded externally in the form of research grants to physician-researchers.
Even critics admit that industry-sponsored research can yield medically important findings, but many charge that things have gotten out of hand. Through its largess, most commonly by funding clinical trials, drug companies (and medical device manufacturers to a smaller degree) have insinuated themselves as integral participants in drug research at academic medical centers. The modern university sanctions the bond by fostering a kind of scientific entrepreneurship among faculty. “The pressure didn’t come from industry saying you must take this money and work with us,” says Don Stein, professor of emergency medicine and author of Buying in or Selling Out: The Commercialization of the American Research University. “Pressures came from university administrators saying that if you want to do any kind of research you’ve got to get outside money, and if you don’t get it, sooner or later we’re going to toss you out of here.” Drug companies also pay for fellowships, continuing medical education programs, speakers bureaus, and lots of drug samples for physicians to hand out to patients. Detractors allege that all of these introduce the potential for investigator bias—and worse.
In his October 10 State of the School Address, Thomas Lawley, dean of the medical school, summed up the overarching schism: “Research conflicts have the potential to bias not only the outcome of the research but also the delivery of patient care. We as an institution and as individual faculty investigators must be extremely careful to prevent even the appearance that these conflicts might affect our judgment. The problem is that academia and industry have fundamental differences in their motives that can never be fully reconciled.” He went on to say that one is driven by a professional, social, moral, and educational obligation to their various constituencies; the other by the pursuit of profits.
It takes surprisingly little to alter a person’s behavior. In his book On the Take, Jerome Kassirer, a physician and past editor-in-chief of the New England Journal of Medicine, describes the “rule of reciprocation,” a powerful social force that impels people to repay favors, no matter how trivial. (Kassirer also remarks that “gifts” from drug companies are no such thing, but are “marketing ploys intended at a minimum to ingratiate the drug representative to the doctor.”)
“You’d be amazed how little it takes to influence people,” says Howard Kushner, Nat C. Robertson Distinguished Professor in the Institute of Liberal Arts and School of Public Health. His solution: “If you’re a researcher, don’t take gifts of any kind, from a fountain pen to a lunch. Drug companies can give whatever they want but no one has to take it. Everyone is being paid a salary anyway, so there’s no need to take gifts. We’re not talking about starving people.” Kushner’s paper, “The Other War on Drugs: The Pharmaceutical Industry, Evidence-Based Medicine, and Clinical Practice, will appear in the winter 2007 issue of the Journal of Policy History.
“I would approve of that statement,” responds Peter Block, an interventional cardiologist and professor of internal medicine, and medical director of the School of Medicine Clinical Trials Office, “but there are practical problems one needs to understand. To ensure that the next generation of physicians who come along will be trained as well as I can train them, I need a lot of things, such as journal clubs to review important articles and meetings to review teaching materials, angiograms, and procedures that we’ve done. These cost money. You have to pay for a lunch if that’s what it takes to get physicians together. Journal clubs are frequently done over dinner [paid for by a drug or device company]. Do I feel beholden to a company for buying lunch? I do not. The topic of that meeting might in fact have nothing to do with their drug or device, which is what I’d prefer.” Block emphasizes that when investigators fully disclose extenuating corporate relationships, they serve fair warning to their peers. “In clinical trials, the data speak for themselves. As long as you carefully review the results and don’t just accept some else’s interpretation—if you look hard at the data—you’ll come up with the truth.”
Some researchers, though, are wary of the way some of that data is gathered to begin with, and with what they consider the industry’s blatant manipulation of the clinical trial process itself. Drug companies frequently pay for, design, and coordinate multicenter trials—trials that follow a single plan and are conducted at more than one medical center. They enlist anywhere from a handful to dozens of geographically scattered researchers who conduct the clinical work piecemeal. The sponsor tabulates and analyzes the data and even decides whether or not to submit the final product to a medical journal for consideration. All of the participants are listed as co-authors on the paper, which may actually have been composed by in-house medical writers. Contractually, the sponsor controls the disposition of the results. In one trial of an antipsychotic medication for bipolar disorder, Ghaemi noticed that even though the data clearly showed that the primary outcome exposed flaws in the drug’s efficacy, the draft of the paper sent to him to review downplayed that fact. “I gave them option of rewriting the analysis or taking my name off the paper. To their credit they changed it, but they were reluctant,” he says, adding that sponsors frequently refuse to let him see the aggregate study data, claiming it is proprietary and therefore not subject to outside evaluation.
Burying the evidence?
The outcome of industry-sponsored multicenter trials is usually known to the sponsors because they frame the questions and devise the methodology. And in the unlikely event that results disappoint, the sponsor can simply bury the results by withholding a paper from publication—a practice that some researchers detest. Investigators and institutions can challenge that strategy by demanding that sponsors release study results to the FDA and the public after a reasonable delay to protect intellectual property, says Stein. “Maybe it’s time for universities to set standards requiring full disclosure for drug or device research, stipulating that at some point after a trial is complete all data must be openly recorded and published, regardless of the results.” The obvious danger is that drug companies will seek out centers with less restrictive rules. “That’s their moral choice, and maybe it should be that if you choose to work at Emory you may have to accept stricter conflict-of-interest criteria. Another approach would be for medical journals to consider only papers that are written by researchers themselves. The momentum for the hundreds of medical journals to change their policies could be started by leading publications, such as the New England Journal of Medicine and the Journal of the American Medical Association. Still better, Stein says, would be for the American Association of Medical Colleges to establish guidelines so that schools couldn’t be played off against one another.
For now, the burden of reducing conflict of interest may fall disproportionately to individual researchers, said Ghaemi, who says he’s doing far fewer promotional talks for drug companies and accepts industry funding mainly for continuing medical education-accredited lectures and for investigator-initiated trials in which he controls the design and the data. (Even then, he senses that if a drug company is unhappy with the results there’s a likelihood that they won’t fund future work.) “Researchers and academics in general need to be more self-critical, and we need to get our own house in order,” he says. “If we don’t, then outside forces will. We’re already seeing a strong public opinion backlash; people are less trusting of academic medicine because of these issues. Critics say we are being influenced and don’t realize it—that drug companies are smarter than we are and know a lot more about human psychology than we think, and they’re probably right about that to some extent.”—S.F.