Jennifer Washburn: Hired Education. A hidden culprit in the Drug scandals: the increasingly corporatized university

Jennifer Washburn: Hired Education. A hidden culprit in the Drug scandals: the increasingly corporatized university

M. Michael Wolfe, a gastroenterologist at Boston University, admits he was duped by the Pharmacia Corporation, the manufacturer of the blockbuster arthritis drug Celebrex. (In 2003, the company was purchased by P?zer.) In the summer of 2000, The Journal of the American Medical Association asked Wolfe to write a review of a study showing that Celebrex was associated with lower rates of stomach and intestinal ulcers and other complications than two older arthritis medications, diclofenac and ibuprofen. Wolfe found the study, tracking 8,000 patients over a six-month period, persuasive, and penned a favorable review, which helped to drive up Celebrex sales.

But early the next year, while serving on the Food and Drug Administration’s (FDA) arthritis advisory committee, Wolfe had occasion to review the same drug trial again, and was ?abbergasted by what he saw. Pharmacia’s study had run for one year, not six months, as the company had originally led both Wolfe and the Journal to believe. When the complete data was considered, most of Celebrex’s advantages disappeared because the ulcer complications that occurred during the second half of the study were disproportionately found in patients taking Celebrex.

“I am furious,” Wolfe told The Washington Post in 2001. “I looked like a fool. But ... all I had available to me was the data presented in the article.” Remarkably, none of the Journal study’s 16 authors, including eight university professors, had spoken out publicly about this egregious suppression of negative data. All the authors were either employees of Pharmacia or paid consultants of the company.

Celebrex, an anti-in?ammatory drug similar to Vioxx, is once again in the news due to concerns that it may be associated with the same cardiovascular risks that caused Vioxx to get yanked from the market. In recent months, we’ve heard a great deal about con?icts of interest at both the FDA, the agency that approves drugs for public safety, and the National Institutes of Health, where publicly funded scientists moonlight as consultants for the very companies that manufactured the drugs they are testing. Still largely ignored, however, is the role played by the once-autonomous ivory tower and the university scientists who, either knowingly or unknowingly, facilitate the pharmaceutical industry’s manipulation of drug testing by lending it an aura of objectivity.

Today, market forces are dictating what is happening in the world of higher education as never before, causing universities to look and behave more and more like business enterprises. Instead of honoring their traditional commitment to teaching, disinterested research, and the broad dissemination of knowledge, universities are aggressively striving to become research arms of private industry. Faced with declining government funding, they are avidly seeking to enhance their role as “engines” of economic growth, promising state legislators and governors that they will help drive regional economic development by pumping out commercially valuable inventions.

This radical rede?nition of the university’s mission can be traced back to the economic stagnation of the 1970s. Propelled by heightened competition from Germany and Japan, Congress passed landmark legislation in 1980 that allowed universities to automatically retain the rights to intellectual property stemming from taxpayer-?nanced research. The intent of the legislation, popularly known as the Bayh-Dole Act (its sponsors were Senators Birch Bayh and Bob Dole), was to stimulate innovation and speed the transfer of federally ?nanced research to industry. What it accomplished in the process was the introduction of a dangerous new pro?t motive into the heart of the university.

As a result, schools now routinely operate expensive patenting and licensing operations to market their faculty’s inventions, extracting royalty income and other fees in return. They invest their endowment money in risky startup ?rms founded by their professors. They run their own industrial parks and venture capital funds. They publish newsletters encouraging faculty members to commercialize new research by launching independent, faculty-owned companies. Star professors consult for, or hold equity in, the same ?rms that manufacture the drugs they are studying, while also often accepting generous fees to join corporate advisory boards and speakers’ bureaus. Sometimes these professors even hold the patent to the drug or device being tested. In a study of 800 scienti?c papers published in leading journals of medicine and molecular biology, Sheldon Krimsky, a professor of public policy at Tufts University, found that slightly more than a third of the lead authors based at research institutions in Massachusetts had a signi?cant ?nancial interest in their own reports. So pervasive are such ties that journal editors now frequently complain that they can no longer ?nd academic experts who do not have a ?nancial interest in a drug or therapy the journal would like to review.

Research suggests that publicly funded science, most of it performed at universities, was a critical contributor to the discovery of nearly all of the 25 most important breakthrough drugs introduced between 1970 and 1995. If university scientists lose their independence, who will perform this pathbreaking research and objectively evaluate the safety and effectiveness of drugs already on the market? Con?icts of interest are more than an academic concern. When it comes to health policy, they pose a serious threat to public health.

With the possible exception of business schools, the nation’s medical schools have been more in?ltrated by industry than any other sector of the university. Pharmaceutical companies sponsor daily lunches for medical students at which they market their latest drugs; they ply professors with fancy dinners, gifts, luxurious trips, and free prescriptions designed to in?uence medical decisions and prescribing habits. The drug industry also spends millions of dollars ?nancing clinical drug research at the academy, but increasingly this money comes with many more strings attached. After conducting a thorough review of the medical literature for The New England Journal of Medicine in 2000, Thomas Bodenheimer, an internist at the University of California, San Francisco, concluded that academic investigators were rapidly ceding to industry control over nearly every stage of the clinical research process.

In the past, for example, it was common for university scientists to initiate the research protocol. Now, studies are frequently conceived and designed in the company’s own pharmacological and marketing departments, thus removing this formative stage of the research from academic hands almost entirely. The company then shops the study around to various academic institutions (and a growing number of competing for-pro?t subcontractors that run clinical trials) in search of investigators to conduct the research. As university medical schools have grown more dependent on industry grants to sustain their operations, their professors have become increasingly willing to accept an industry-initiated protocol without modi?cation, even though the study may be largely designed to secure a company’s market position. Should a professor reject the study or insist on changes, another university scientist will very likely be more solicitous.

Industry also encourages the use of ghostwriters on scienti?c papers. This means an article or review bylined by a prominent academic might in fact have been written by a medical-communications company working for the drugmaker, with the “author” paid an honorarium to attach his or her name to it.

When Wyeth-Ayerst sought to boost market demand for Redux, one part of the once highly popular “fen-phen” diet-drug combination, the company hired a company called Excerpta Medica to help draft the manuscripts and pay doctors to review and sign the articles. One of the many doctors who signed Excerpta’s papers was Richard Atkinson, a renowned obesity expert at the University of Wisconsin-Madison. Atkinson denied having any knowledge of Excerpta’s connection to Wyeth, but as an independent academic, he nonetheless agreed to lend his name to a company he apparently knew little about. (Excerpta maintains that all its authors were told of the company’s association with the manufacturer.) In a deposition on January 15, 1999, Wyeth-Ayerst executive Jo Alene Dolan admitted that her company had written the article for Atkinson, stressing that all drug companies ghostwrite articles. Shortly before the article could be published, Redux was pulled from the market because of its association with serious heart and lung problems.

Scientists who perform industry-sponsored research are also asked routinely to sign legal contracts requiring them to keep both the methods and the results of their work secret for a period of time. Research conducted by David Blumenthal and Eric Campbell, health-policy researchers at Harvard University, suggests that data withholding and publication delays have become far more common over the last 25 years, particularly in molecular biology, medicine, and other life-science disciplines, where commercial relationships have grown dramatically in recent years. In a survey of 2,167 life-science faculty, Blumenthal found that nearly one in ?ve of them had delayed publication for more than six months to protect proprietary information.

Industry also manipulates academic research by suppressing negative studies altogether. Recently, it came to light that a whole class of popular antidepressants -- including such heavily prescribed drugs as Paxil, Zoloft, and Prozac -- are largely ineffectual in treating childhood depression and actually increase the risk of suicide. One of the main reasons this information was not available to doctors and the broader public, it turns out, is that the academic investigators who led these studies either allowed industry to bury their research or were complicit in downplaying negative ?ndings in their own published papers. How prevalent is such corporate meddling? The question has received surprisingly little scholarly attention, but what research does exist is not encouraging. One survey of major university-industry research centers in the ?eld of engineering, for example, found that 35 percent would allow corporate sponsors to delete information from papers prior to publication.

But all the blame for the eroding objectivity of university researchers does not rest with industry. Universities themselves are complicit: They are so ?nancially invested in their professors’ research through patents, equity, and other ?nancial holdings that their disinterested pursuit of knowledge has been gravely compromised. For instance, when the Harvard Center for Risk Analysis’ longtime director, Professor John D. Graham, was nominated by President George W. Bush to become the government’s “regulatory czar” at the Of?ce of Information and Regulatory Affairs (part of the Of?ce of Management and Budget), it helped to expose just how extensive Harvard’s ?nancial con?icts really were. Congressional hearings revealed that Graham’s center solicited tobacco money and worked with the tobacco industry to disparage the risks of secondhand smoke. (Harvey Fineberg, a dean at the Harvard School of Public Health, demanded that one check from Philip Morris be returned. In response, Graham wrote to the company asking if it might send the $25,000 back to the Harvard center via the Philip Morris subsidiary Kraft Foods instead.) Graham’s center also argued that cell-phone use by drivers should not be restricted, even though its own research, which was funded by AT&T Wireless Communications, showed that such use could lead to a thousand additional highway deaths a year. As a member of the Environmental Protection Agency’s scienti?c advisory board subcommittee on dioxin, a known human carcinogen, Graham argued that reducing dioxin levels might “do more harm … than good.” His Harvard center, meanwhile, was heavily funded by dioxin producers.

Worse yet, the universities’ loyalties are now so con?icted that schools are increasingly willing to cave in to narrow commercial demands rather than defend their own professors’ academic freedom or the public interest. When researchers at the University of Utah discovered an important human gene responsible for hereditary breast cancer, for example, they didn’t make it freely available to other scientists, even though we -- the U.S. taxpayers -- paid $4.6 million to ?nance the research. The university raced to patent it, then granted the monopoly rights to Myriad Genetics Inc., a startup company founded by a University of Utah professor, which proceeded to hoard the gene and prevent other academic scientists from using it.

Professors, too, are increasingly driven by the bottom line. More and more, they not only accept industry grants to support their research but also hold stock in or have other ?nancial ties to the companies funding them. Many experts fear this skewing of professors’ research toward short-term commercial goals will impede long-term scienti?c and technological innovation. Financial entanglements between researchers and corporations have grown so common that the Securities and Exchange Commission (SEC) has investigated numerous academic researchers suspected of engaging in insider trading. In a case ?led in Pennsylvania, the SEC charged Dale J. Lange, a Columbia University neurologist, with pocketing $26,000 in pro?ts after Lange bought stock in a company that was about to release promising new ?ndings concerning a drug to treat Lou Gehrig’s disease. Lange had good reason to expect the stock to soar because he had conducted the con?dential clinical trials himself. In 2000, an investigation by USA Today found that more than half the experts hired to advise the U.S. government on the safety and effectiveness of drugs -- a large number of whom are academics -- now have ?nancial links to companies that will be affected by their conclusions. When Wyeth-Ayerst was trying to get its diet drug, Redux, approved for sale in the United States, for example, it faced a serious hurdle: Patients in Europe who had taken a drug virtually identical to Redux had an increased chance of getting a rare, life-threatening lung ailment known as pulmonary hypertension. To combat this negative health pro?le, the company packed an FDA hearing room with a who’s who list of the nation’s top academic obesity experts, all of whom were also paid consultants to Wyeth-Ayerst or other companies involved in the sale of Redux. In addition, the company recruited expert “opinion leaders,” such as George Blackburn, a renowned obesity expert at Harvard, to testify before the Medical Society of Massachusetts for approval of the drug. Blackburn and other academic luminaries further participated in the company’s “Visiting Important Professors Program” and were paid thousands of dollars in honoraria to ?y to fancy resorts and promote Redux at medical conferences. Not surprisingly, the drug handily won market approval, and prescriptions in the United States began to soar.

Soon, however, evidence of the drug’s association with lung damage surfaced once again, and the company turned to leading university scientists to do damage control. In the summer of 1996, an internal company memo revealed that the company was planning to spend $5.8 million to pay for more university-based studies, noting that that money was needed to “establish and maintain relationships with opinion leaders at the local and national level to communicate to their colleagues the bene?ts of Redux and to encourage its use.” Among the many doctors willing to heed the company’s call was Atkinson, the obesity expert at the University of Wisconsin, whose name appeared on a company-authored article. “Let me congratulate you and your writer,” wrote Atkinson in a thank-you letter to the ghostwriting ?rm that was one of numerous company documents that became public during subsequent legal proceedings. “Perhaps I can get you to write all my papers for me!”

So how does this growing web of academic-industry ties affect research outcomes? A vast body of work suggests that industry-funded research is far from impartial. In 1996, Stanford researcher Mildred Cho co-authored a study in the Annals of Internal Medicine that found that 98 percent of papers based on industry-sponsored research re?ected favorably on the drugs being examined, compared with 79 percent of papers based on research not funded by industry. An analysis published in The Journal of the American Medical Association in 1999 found that studies of cancer drugs funded by the pharmaceutical industry were nearly eight times less likely to reach unfavorable conclusions than similar studies funded by nonpro?t organizations. More recently, a systematic review of 1,140 clinical trial studies, published by researchers at Yale in 2003, concluded that, from cancer to arthritis to cholesterol, the evidence is overwhelming that when research is industry-sponsored, it is “signi?cantly more likely to reach conclusions that [are] favorable to the sponsor” than non-industry-funded research.

In the area of health and drug research, of course, the results of such manipulation can be deadly. Running down the list of drugs recently pulled from the market or subject to increased health warnings -- Rezulin, the diabetes drug; Redux (or fen-phen), the diet drug; Retin-A, the anti-wrinkle cream; Neurontin, the epilepsy drug; Paxil, Zoloft, and the many other antidepressants now deemed ineffective for children -- one ?nds that a remarkable number of prominent university professors with close ?nancial ties to the manufacturers played a central role in lobbying for these drugs to be approved, recommending them to other doctors, and, in many cases, urging that they remain on the market long after the problems or lack of effectiveness became known. Not infrequently, the university scientists who shill for the drug companies most aggressively are also the biggest-name professors in their ?elds.

Universities have gone out of their way to assure the public that their clinical trials meet the highest standards of “scienti?c excellence” and “academic rigor.” But over the last 20 years, public dismay over the growing ?nancial entanglements in clinical research has prompted the federal government to impose tougher con?ict-of-interest regulations, only to encounter ?erce university opposition. In 1995, the federal government ?nally succeeded in pushing through rules that would apply to all academic researchers funded by the Department of Health and Human Services (HHS) or the National Science Foundation (NSF). But the rules, which remain in place today, were not tough enough to be effective. Although they mandate that serious con?icts of interest must be managed and/or eliminated, they leave the determination of what action is to be taken, if any, entirely up to the university. The policy also doesn’t provide any guidance on which con?icts warrant serious attention, nor does it impose any prohibitions, such as banning ?nancial con?icts outright in the area of human-subject research. Signi?cantly, the policy also says nothing about institutional con?icts of interest.

The result, not surprisingly, is that university con?ict-of-interest rules vary widely. One comprehensive 2000 survey of the written policies at 100 academic institutions found that only 55 percent of schools required disclosure of con?icts of interest from all faculty, and only 19 percent speci?ed any limits on researchers’ ?nancial ties to corporate sponsors. Worse yet, under this fragmented system, there is enormous pressure on universities to keep their policies lax. Schools with tighter restrictions run the risk of losing talented faculty to competing schools with more permissive policies, where the ?nancial rewards and commercial prospects are likely to be greater.

Another conspicuous problem with the HHS/NSF policy is that it does not require universities to make any of the information they compile on faculty ?nancial con?icts available to the public. Many academic journals do require their authors to disclose corporate ?nancial ties. But in practice, reporting is astonishingly poor. In a 2001 study, Tufts’ Krimsky found that a mere 0.5 percent of the 61,134 papers appearing in 181 peer-reviewed journals contained statements about the authors’ ?nancial ties. More recent studies have found similarly low levels of reporting.

In some respects, the whole debate re?ects how far the academic world remains from dealing seriously with the issue; disclosure of potential con?icts of interest is, after all, a far cry from eliminating them outright, as many professions not only recommend but also require. In the legal profession, for example, attorneys are prohibited from taking on cases in which they have a ?nancial interest or other explicit con?icts that might be seen to compromise their professional integrity. The same is true of judges. But when it comes to academia, neither the medical community nor the government (whether through Congress or the regulatory agencies) has taken up the task, instead proceeding under the assumption that universities can be trusted to manage these commercial interactions themselves. It’s a nice idea. But are academic institutions really capable of performing this function? There is good reason to be skeptical: Far from being independent watchdogs capable of dispassionate inquiry, universities are increasingly joined at the hip to the very market forces the public has entrusted them to check, creating problems that extend far beyond the research lab.

The American Prospect  (reproducido en New America Foundation), 04/02/05