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At first I thought: "What's the use?"

but then two friends pointed out an article by Marcia Angell about the Pharma/Academic Health Sciences interface. This matter has been consistently ignored by the AHC/Medical School at the University of Minnesota for going on three years.

So I post:

Big Pharma, Bad Medicine

How corporate dollars corrupt research and education

Marcia Angell

In May of 2000, shortly before I stepped down as editor-in-chief of the New England Journal of Medicine, I wrote an editorial entitled, "Is Academic Medicine for Sale?" It was prompted by a clinical trial of an antidepressant called Serzone that was published in the same issue of the Journal.

The authors of that paper had so many financial ties to drug companies, including the maker of Serzone, that a full-disclosure statement would have been about as long as the article itself, so it could appear only on our Web site. The lead author, who was chairman of the department of psychiatry at Brown University (presumably a full-time job), was paid more than half a million dollars in drug-company consulting fees in just one year. Although that particular paper was the immediate reason for the editorial, I wouldn't have bothered to write it if it weren't for the fact that the situation, while extreme, was hardly unique.

Academic medical centers are charged with educating the next generation of doctors, conducting scientifically important research, and taking care of the sickest and neediest patients. That's what justifies their tax-exempt status. In contrast, drug companies--like other investor-owned businesses--are charged with increasing the value of their shareholders' stock. That is their fiduciary responsibility, and they would be remiss if they didn't uphold it. All their other activities are means to that end. The companies are supposed to develop profitable drugs, not necessarily important or innovative ones, and paradoxically enough, the most profitable drugs are the least innovative. Nor do drug companies aim to educate doctors, except as a means to the primary end of selling drugs. Drug companies don't have education budgets; they have marketing budgets from which their ostensibly educational activities are funded.

This profound difference in missions is often deliberately obscured--by drug companies because it's good public relations to portray themselves as research and educational institutions, and by academics because it means they don't have to face up to what's really going on.

No area of overlap between industry and academia is more important than clinical trials. Unlike basic medical research, which is funded mainly by the National Institutes of Health (NIH), most clinical trials are funded by the pharmaceutical industry. In fact, that is where most pharmaceutical research dollars go.

Since drug companies don't have direct access to human subjects, they've traditionally contracted with academic researchers to conduct the trials on patients in teaching hospitals and clinics. That practice continues, but over the past couple of decades the terms and conditions have changed dramatically.

The major drug companies are now hugely profitable, with net incomes consistently several times the median for Fortune 500 companies. In fact, they make more in profits than they spend on research and development (R&D), despite their rhetoric about high prices being necessary to cover their research costs. (They also spend twice as much on marketing and administration as they do on R&D.) The reasons for the astonishing profitability of these companies aren't relevant here, but suffice it to say that as a result the industry has acquired enormous power and influence. In contrast, medical centers have fallen on difficult times (or so they believe), mainly because of shrinking reimbursements for their educational and clinical missions. To a remarkable extent, then, medical centers have become supplicants to the drug companies, deferring to them in ways that would have been unthinkable even twenty years ago.

Often, academic researchers are little more than hired hands who supply human subjects and collect data according to instructions from corporate paymasters. The sponsors keep the data, analyze it, write the papers, and decide whether and when and where to submit them for publication. In multi-center trials, researchers may not even be allowed to see all of the data, an obvious impediment to science and a perversion of standard practice.

Much of the time, the institutional conflict-of-interest rules ostensibly designed to control these relationships are highly variable, permissive, and loosely enforced. At Harvard Medical School, for example, few conflicts of interest are flatly prohibited; they are only limited in various ways. Like Hollywood, academic medical centers run on a star system, and schools don't want to lose their stars, who are now accustomed to supplementing their incomes through deals with industry.

Schools, too, have deals with industry. Academic leaders, chairs, and even deans sit on boards of directors of drug companies. Many academic medical centers have set up special offices to offer companies quick soup-to-nuts service. Harvard's Clinical Research Institute (HCRI), for example, originally advertised itself as led by people whose "experience gives HCRI an intimate understanding of industry's needs, and knowledge of how best to meet them"--as though meeting industry's needs is a legitimate purpose of an academic institution.

Much of the rationalization for the pervasive research connections between industry and academia rests on the Bayh-Dole Act of 1980, which has acquired the status of holy writ in academia. Bayh-Dole permits--but does not require, as many researchers claim--universities to patent discoveries that stem from government-funded research and then license them exclusively to companies in return for royalties. (Similar legislation applies to work done at the NIH itself.) In this way, academia and industry are partners, both benefiting from public support.

The result of Bayh-Dole was a sudden, huge increase in the number of patents--if not in their quality. And the most prestigious academic centers now have technology-transfer offices and are ringed by start-up companies. Most technology-transfer offices at academic medical centers don't make much money, but every now and then one strikes it rich. Columbia University, for example, received nearly $300 million in royalties from more than 30 biotech companies during the seventeen-year life of its patent on a method for synthesizing biological products. Patenting and licensing the fruits of academic research has the character of a lottery, and everyone wants to play.

A less-appreciated outcome of Bayh-Dole is that drug companies no longer have to do their own creative, early-stage research. They can, and increasingly do, rely on universities and start-up companies for that. In fact, the big drug companies now concentrate mainly on the late-stage development of drugs they've licensed from other sources, as well as on producing variations of top-selling drugs already on the market--called "me-too" drugs. There is very little innovative research in the modern pharmaceutical industry, despite its claims to the contrary.

Increasingly, industry is setting the research agenda in academic centers, and that agenda has more to do with industry's mission than with the mission of the academy. Researchers and their institutions are focusing too much on targeted, applied research, mainly drug development, and not enough on non-targeted, basic research into the causes, mechanisms, and prevention of disease.

Moreover, drug companies often contract with academic researchers to carry out studies for almost entirely commercial purposes. For example, they sponsor trials of drugs to supplant virtually identical ones that are going off patent. And academic institutions are increasingly focused on the Bayh-Dole lottery. A few years ago, the Dana Farber Cancer Institute sent Harvard faculty an invitation to a workshop called "Forming Science-Based Companies." It began:

So you want to start a company? Join the Provost, Harvard's Office for Technology and Trademark Licensing (OTTL), leading venture capitalists, lawyers and entrepreneurs for a conference on the basics of forming a start-up based on university technology
.

There's a high scientific opportunity cost in serving the aims of the pharmaceutical industry. For example, new antibiotics for treating infections by resistant organisms are an urgent medical need, but are not economically attractive to industry because they are not likely to generate much return on investment.

In addition to distorting the research agenda, there is overwhelming evidence that drug-company influence biases the research itself. Industry-supported research is far more likely to be favorable to the sponsors' products than is NIH-supported research.

An important cause of bias is the suppression of negative results. But clinical trials are also biased through research protocols designed to yield favorable results for sponsors. There are many ways to do that.

Conflicts of interest affect more than research. They also directly shape the way medicine is practiced, through their influence on practice guidelines issued by professional and governmental bodies and through their effects on FDA decisions.

Conflicts of interest are equally troubling in medical education, where industry influence is perhaps greatest and least justified. The pharmaceutical industry devotes much, if not most, of its vast marketing budget to what it calls the "education" of doctors. The reason is obvious: doctors write the prescriptions, so they need to be won over.

Drug companies support educational programs even within our best medical schools and teaching hospitals, and are given virtually unfettered access to young doctors to ply them with gifts and meals and promote their wares. In most states doctors are required to take accredited education courses, called continuing medical education (CME), and drug companies contribute roughly half the support for this education, often indirectly through private investor-owned medical-education companies whose only clients are drug companies. CME is supposed to be free of drug-company influence, but incredibly these private educators have been accredited to provide CME by the American Medical Association's Accreditation Committee for Continuing Medical Education--a case of the fox not only guarding the chicken coop, but living inside it.

If drug companies and medical educators were really providing education, doctors and academic institutions would pay them for their services. When you take piano lessons, you pay the teacher, not the other way around. But in this case, industry pays the academic institutions and faculty, and even the doctors who take the courses. The companies are simply buying access to medical school faculty and to doctors in training and practice.

This is marketing masquerading as education. It is self-evidently absurd to look to companies for critical, unbiased education about products they sell. It's like asking a brewery to teach you about alcoholism, or a Honda dealer for a recommendation about what car to buy.

What should be done about all of this? So many reforms would be necessary to restore integrity to medical research, education, and practice that they can't all be summarized here. Many would involve congressional legislation and changes in the FDA, including its drug-approval process. But the medical profession also needs to wean itself from industry money almost entirely.

For some time now, I've been recommending these three essential reforms:

First, members of medical school faculties who conduct clinical trials should not accept any payments from drug companies except research support, and that support should have no strings attached.

Second, doctors should not accept gifts from drug companies, even small ones, and they should pay for their own meetings and continuing education. Other professions pay their own way, and there is no reason for the medical profession to be different in this regard.

Finally, academic medical centers that patent discoveries should put them in the public domain or license them inexpensively and non-exclusively, as Stanford does with its patent on recombinant DNA technology based on the work of Stanley Cohen and Herbert Boyer. Bayh-Dole is now more a matter of seeking windfalls than of transferring technology. Some have argued that it actually impedes technology transfer by enabling the licensing of early discoveries, which encumbers downstream research. Though the legislation stipulates that drugs licensed from academic institutions be made "available on reasonable terms" to the public, that provision has been ignored by both industry and academia. I believe medical research was every bit as productive before Bayh-Dole as it is now, despite the lack of patents. I'm reminded of Jonas Salk's response when asked whether he had patented the polio vaccine. He seemed amazed at the very notion. The vaccine, he explained, belonged to everybody. "Could you patent the sun?" he asked.

And to those academic researchers who think the current path is just fine,
I have this to say: no, it is not necessary to accept personal payments from drug companies to collaborate on research. There was plenty of innovative research before 1980--at least as much as there is now--when academic researchers began to expect rewards from industry. And no, you are not entitled to anything you want just because you're very smart. Conflicts of interest in academic medicine have serious consequences, and it is time to stop making excuses for them.


Dr. Cerra, how long are you going to ignore common sense?

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