from BostonReview Website
It was prompted by a clinical trial of an antidepressant called Serzone that was published in the same issue of the Journal.
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.
One asked rhetorically,
The second went further:
The author didn’t feel he had to say who the current owner was.
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.
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. That’s because the Food and Drug Administration (FDA) will not approve a drug for sale until it has been tested on human subjects.
Pharmaceutical companies must show the FDA that a new drug is reasonably safe and effective, usually as compared with a placebo. That requires clinical trials, in which treatments are compared under rigorous conditions in a sample of the relevant population. The results of drug trials (there may be many) are submitted to the FDA, and if one or two are positive - that is, they show effectiveness without serious risk - the drug is usually approved, even if all the other trials are negative.
Sponsors had no part in designing or analyzing the studies, they did not claim to own the data, and they certainly did not write the papers or control publication. Grants were at arm’s length.
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.
These are the people who write textbooks and medical-journal papers, issue practice guidelines (treatment recommendations), sit on FDA and other governmental advisory panels, head professional societies, and speak at the innumerable meetings and dinners that take place every day to teach clinicians about prescription drugs.
In addition to grant support, academic researchers may now have a variety of other financial ties to the companies that sponsor their work.
They serve as consultants to the same companies whose products they evaluate, join corporate advisory boards and speakers bureaus, enter into patent and royalty arrangements, agree to be the listed authors of articles ghostwritten by interested companies, promote drugs and devices at company-sponsored symposia, and allow themselves to be plied with expensive gifts and trips to luxurious settings.
Many also have equity interest in sponsoring companies.
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.
In this way, academia and industry are partners, both benefiting from public support.
The start-up companies are often founded by the researchers and their institutions, and they usually either license their promising products to larger companies or are bought by large companies outright.
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.
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.
So what’s wrong with that? Isn’t this
just the sort of collaboration that leads to the development of
important new medical treatments?
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.
A few years ago, the Dana Farber Cancer Institute sent Harvard faculty an invitation to a workshop called “Forming Science-Based Companies.”
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.
Often, when we rejected studies because of their biases, they turned up in other journals essentially unchanged. And looking back, I now realize that despite our best efforts, we sometimes published biased studies without knowing it.
One problem is that we thought that if studies were subjected to rigorous peer review, it was sufficient to disclose authors’ commercial ties - essentially to tell readers caveat emptor, as in the Serzone study I mentioned earlier.
I no longer believe that’s enough.
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.
The sponsor’s drug may be compared with another drug administered at a dose so low that the sponsor’s drug looks more powerful. Or a drug that’s likely to be used by older people will be tested in young people, so that side effects are less likely to emerge. The standard practice of comparing a new drug with a placebo, when the relevant question is how it compares with an existing drug, is also misleading.
Supporters of the status quo claim that attempts to regulate conflicts of interest will slow medical advances, but the truth is that conflicts of interest distort medical research, and advances occur in spite of them, not because of them.
Research collaboration between academia and industry can be fruitful, but it doesn’t need to involve payments to researchers beyond grant support.
And that support, as I have argued,
should be at arm’s length.
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.
Perhaps most important, many members of the eighteen standing committees of experts that advise the FDA on drug approvals also have financial ties to the industry.
After the painkiller Vioxx was removed from the market in 2005 (it increased the risk of heart attacks), the FDA convened a panel consisting of two of these committees to consider whether painkillers of the same class as Vioxx should also be removed from the market.
Following three days of public hearings, the combined panel decided that, although these drugs - called COX-2 inhibitors - did increase the risk of heart attacks, the benefits outweighed the risks. It therefore recommended that all three of the drugs, including Vioxx, be permitted to remain on the market, perhaps with strong warnings on the labels.
As a result of this embarrassing revelation, the FDA reversed the panel and left only one of the drugs, Celebrex, on the market, with a warning on the label.
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.
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.
The programs feature industry-prepared symposia during free meals, as well as academic talks by faculty during the rest of the day.
The two types of talks are listed separately, but take place at the same meeting, where there is also a gigantic exhibit hall for industry sponsors. The Harvard name and logo figure prominently in Pri-Med’s advertising and at the conferences, in return for which Harvard Medical School receives direct income, as well as payments to participating faculty.
The companies are simply buying access to medical school faculty and to doctors in training and practice.
That industry-sponsored education is a masquerade is underscored by the fact that some of the biggest Madison Avenue ad agencies, hired by drug companies to promote their products, also own their own medical-education companies. It’s one-stop shopping for the industry.
Doctors and their patients come to believe that for every ailment and discontent there is a drug, even when changes in lifestyle would be more effective. And they believe that the newest, most expensive brand-name drugs are superior to older drugs or generics, even though there is seldom any evidence to that effect because sponsors don’t usually compare their drugs with older drugs at equivalent doses.
In addition, doctors are encouraged to prescribe drugs for uses not approved by the FDA (known as “off-label” prescriptions).
In fact, responsibility for its own
education is an essential part of the definition of a learned
Most of the big drug companies have paid huge fines to settle charges of illegal activities. Last year Pfizer pleaded guilty and agreed to pay $2.3 billion to settle criminal and civil charges of marketing drugs for off-label uses - the largest criminal fine in history. The fines, while enormous, are still dwarfed by the profits generated by these activities, and are therefore not much of a deterrent.
Still, apologists might argue that, despite its legal transgressions, the pharmaceutical industry is merely trying to do its primary job - furthering the interests of its investors - and sometimes it simply goes a little too far.
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.
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.
I’m aware that my proposals might seem radical.
That is because we are now so drenched in market ideology that any resistance is considered quixotic. But academic medical centers are not supposed to be businesses. They now enjoy great public support, and they jeopardize that support by continuing along the current path.
Conflicts of interest in academic
medicine have serious consequences, and it is time to stop making
excuses for them.