Corporate involvement in medical research and education: sin or salvation? The answer depends on how you approach the question.
You get one answer if you rely on what you think are self-evident beliefs, akin to religion, to be imposed on all by powerful authorities. You get a very different answer when you look to rigorous scholarly analysis dependent upon empirical facts and logic rooted in practical experience and the canons of history, economics, and the epistemology of science.
One might imagine that universities and governments founded on the principle of separation of church and state would favor the latter approach. Instead, academics and legislators have predominantly followed the former; their policies have a religious flavor, hence sin and salvation.
Since medicine and science merged in the twentieth century, health care expenses have risen exponentially worldwide. While technology is what drives up costs, the costs of the technologies themselves represent less than 15 percent of the total. If companies making the technologies gave them away for free, there would be little change in overall expense.
The sources of money for medical innovation and education have evolved over time from personal wealth and patronage to charitable giving, government subsidy, and, most recently, industry. Industry funding is considered tainted by some, but it is not the first source of investment to be so designated. The fact is that all sources are tainted: taint enough. There is never enough money to support the possible missions of universities. For this reason alone, any money for health care innovation and education is salvation.
Medical research cannot do without industry supportat least, not as well as it has since that relationship began. Industry investment in research tracks perfectly with extended longevity. This adaptive evolution contrasts with public, mostly National Institutes of Health (NIH), funding. Political vagaries and spending limits constrain the Institutes ability to promote health. The only realistic supply of added funding is from industry, which currently provides less than 6 percent of university research funding. Without industry, there is no one to fill the gap: last year, when industry payments for Continuing Medical Education (CME) fell by over $175 million, the total available funding for that activity fell by 7 percent.
Industry involvement in medicine continues to evolvea good thing, because it creates efficiency. But that evolution is complex. To really appreciate the role of corporate money in innovation and education demands a nuanced understanding of arcane technical details. The failure to address this evolving complexity makes industry support for medical science an easy target for demonization, which has contaminated policy efforts.
Opponents of industrys role in medicine seem to ignore the tremendous value that industry generates. I define value as increasing longevity, reducing pain, and improving quality of life from a health standpoint. Much evidence attests to markedly enhanced value, so defined, since industry began taking greater responsibility for medical advances.
In the last 40 years, mortality from cardiovascular disease has fallen steadily by about half. Cancer mortality has remained flat in absolute terms and, relative to population, is at an all-time low. Many factors contribute to this incremental reduction in mortality, but according to economists such as Harvards David Cutler and Columbias Frank Lichtenberg, products produced by industry are the most important.
Still, does industry deserve the credit? One might contend that the NIH mines the gold that companies then take to the bank. This is false. As analyses by the Congressional Research Office and the NIH itself show, return on public investment has been amplified many-fold by industry contributions. Paid collaboration between physicians, academics, and industry shows its benefits in these appreciated returns.
Value is driven by innovation, and innovation in medicine is extremely difficult, for reasons both external and internal to research. Externally, it is heavily regulated by FDA oversight, litigation threats from the Office of the Inspector General, and the laws of product liability.
The list of substantive incidents of fraud is strikingly short, especially in the context of the benefits of industry involvement.
Internally, and most important, is our ignoranceabout which we can do little. Scientists study chemicals that they believe have great prospects, yet only one in roughly 5,000 becomes a drug. And that after sixteen years of research, on average, and billions of dollars spent.
John Ioannidis, a physician and health-policy expert, surveyed more than 25,000 articles in high-profile biomedical journals and found that only 101less than 0.4 percenteven mention a practical medical possibility. Twenty-one of those 101 possible applications were tested in clinical trials. There were five FDA approvals from those trials, and one product is in use today.
These dreary statistics do not arise from a lack of good intentions, or from greed. They are a consequence of natures inscrutability, overcome only by immense trial and error. Industry profitability enables that effort through investment. (In Ioannidiss study, authors with industry connections were eight times more likely to see their ideas brought to clinical trial.) Lack of profit seriously slows innovation by limiting investment.
The history of biotechnology entrepreneurship illustrates these limits. The prominent academics involved in early biotech are the few who have made a lot of moneydeservedly so, not so much because of specific inventions, but because by straddling academe and industry, these researchers retained the credibility that unlocked investment from venture capital. Their networks facilitated talent recruitment and other technical contributions to product development. However, in the aggregate, biotechnology profitability has been zero or less than zero until recently because of inadequate investment. Many potentially lifesaving technologies are languishing in the pipeline, especially now, with the investment ecosystem dried up by recession and paralyzed bank lending.
I dont know how to make medical innovation and education easier, but do we want to make it harder, as further obstacles to the relationship between industry and academia would ensure?
A vast literature consisting of medical-journal articles, books, news reports, and even movies abruptly appeared in the late 1980s charging the corruption of medical science under the code term conflict of interest. Conflict of interest is a meaningless epithet, a framing bias implying that risks necessarily eclipse benefits and that conflicts must therefore be managed. Our countrys founders rejected such management. In Federalist 10 James Madison described the removal of conflicts (or factions, as he called them) as a violation of liberty, a remedy . . . worse than the disease. We should address effects of conflicts with checks and balances, not conflicts per se. That is good policy.
But health care has gone a different way: instead of punishing speeders, we have moved to banning fast cars prophylactically.
We now have academic and state regulations that invade privacy and mandate mass confession (disclosure), restrict freedom of speech (researchers who work with companies cannot discuss company products in high-profile medical journals), limit freedom of association (physicians can meet with company marketers only in prescribed settings), and undermine rewards for excellence (payments for value-enhancing services are capped or eliminated). The controls do, however, empower some members of the profession: unaccountable authorities. Rather than allow entrepreneurial faculty to raise industry funds for their specific research and education activities, academic administrators expect industry to donate unrestricted monies for them to distribute as they see fit.
These regulations have all been justified by severe allegations. The accusers argue that industry is inherently corrupt, physicians cannot cope with industry marketing, and industry association for pay is both unethical and alarming to the public.
Are these allegations true?
You would think, considering the size of the health care enterprise and the force of the allegations, wed be awash in corruption. Yet the list of substantive incidents of fraud is strikingly shortespecially in the context of the benefits of industry involvementand the legitimacy of many of the accusations is questionable.
Critics point to researchers failures to disclose corporate relationships in publications and presentations, but these failures cause no demonstrable damages. Critics also cite delayed or non-reporting of research results unfavorable to corporate research sponsors; however, they neglect to mention examples in which economically devastating outcomes were promptly publicized. Over the past 30 years there have been a half-dozen high-profile incidents of alleged wrongdoing ascribed to financial motivations, including the death of a research subject, corporate violation of a researchers academic freedom, and suppression of publication of academics research results unfavorable to a sponsoring company. But no evidence supports the contention that the research subjects death had anything to do with money, and the supposed intrusion against academic freedom was subsequently ascribed to interpersonal academic squabbling, not corporate misbehavior. The charges are grave and unsettling, and so make good headlines, but rarely survive the test of time.
One of the major sources of unnecessary allegations of corruption is the widespread assumption that payments to physicians are likely to result in decisions favoring the payer and that this yields bad outcomes for patients.
An article published in the Journal of the American Medical Association (JAMA) in 2006 by anti-industry activists allied with persons in high administrative positions in medicine, seems to affirm this assumption. Today it is cited by every institutional conflict-of-interest policy and even inspired a write-up in The New York Times. Referring to a 2000 JAMA paper by the psychiatrist Ashley Wazana, the authors state, The systematic review of the medical literature on [industry gift-giving] by Wazana found that an overwhelming majority of interactions had negative results on clinical care. This is not true.
The Wazana paper was a compilation of physician opinions and reports of behavior resulting from interactions with industry marketing. However, Wazana has no information about clinical care, and explicitly says so.
In fact, he documents positive and negative outcomes of industry interactions with physicians. On the positive side is improved ability to identify the treatment for complicated illnesses. On the negative side, nonrational prescribing, based on a single Dutch study. Wazana found that doctors more readily prescribe marketed drugs and are more likely to ask drug benefit plans to cover them. But placing these behaviors, as he does, in the negative column is not justified, because they could benefit patients. Both Wazana and the authors of the subsequent highly influential paper based on his work simply equate negative outcomes with activities they oppose without empirical basis.
Those who would banish industry from medicine do not appreciate that avarice is no longer the deadliest of sins, that capitalism is the engine of prosperity.
Not only are many allegations of corruption false, but consequences allegedly rising from financial relationships of physicians and academics with industry are almost entirely theoretical. Damages from the supposedly adverse incidents have been compared with those attending pederasty, influence peddling in Congress, Ponzi schemes, corporate fraud, and the mortgage meltdown, but the hyperbole is without merit.
This may come as a surprise in light of the huge legal settlements paid by pharmaceutical and device manufacturers for alleged marketing violations. But in Three Felonies a Day, How the Feds Target the Innocent, civil rights lawyer Harvey Silverglate points out that these cases are part of a prosecutorial extortion racket that doesnt address any damages at all. If the companies lose a case of alleged marketing irregularities, they may be disbarred, which means they are prevented from doing business with the federal governmentno Medicare or Medicaid payment for any of the companys products. The companies cannot afford that risk. They have to settle.
One might conclude that the decision to settle justifies the threat of disbarment. But individuals included in indictments dont care about disbarment; they care about their reputations, so they dont settle. They go to court and win easily. Silverglate cites two such cases, involving the pharmaceutical companies TAP and Serono. Although the companies settled, juries rapidly acquitted their employees.
Even if drug manufacturing is practiced properly, education may be compromised. But the doctors who attend the courses dont seem to think it is. Despite widespread speculation to the contrary, there is little perceived bias in commercially supported CME, as indicated by four publications in the past year, including a Cleveland Clinic survey of almost 100,000 CME participants.
Ultimately, the direct, empirical evidence for corruption is extremely thin, hence the false claims.
To those not working directly in medical research, disclosure, voluntary or enforced, appears benign. But in the lab, it becomes an engine of gossip, a means to act out grievances and take political, legal, or personal advantage.
Rules now in force have prevented the formation of start-up companies by restricting financial involvement of inventors with the startups. They have decreased total support of CME by 7 percent. They have diverted time and money from innovation and education to legal and compliance-assurance efforts that grapple with confusing and, for the most part, unenforceable regulations. Although regulation proponents view impediments to corporate promotion to physicians as salutary, if such promotion actually imparts valuable information for patient care, patients will suffer in its absence. Sorting this out is a challenge for researchers, but the recent stiffening of regulations may accelerate recognition of their negative consequences.
Why, despite lack of empirical evidence, faulty logic, and high costs does the drive to separate academics, physicians, and industry succeed in inflicting flawed and potentially damaging policies? The answer lies in ideology surrounding health care and in the politics of academic medicine.
The pernicious ideology of anti-industry advocates results from the confusion of merit and value. Value is what I defined earlier about longevity and life quality, and you access it only with effort and time. Merit is easyit is probably what you believe now. Merit gauges behaviors, which we deem either inherently good or bad regardless of their health impact.
But activities or outcomes declared to be of low merit and therefore categorically corrupt, such as peer-to-peer education of physicians based on specific products (speakers bureaus), have clear value for improving patient care. Though the media only cover the benefits to physicians paychecks, that value is transmitted well beyond the speakers and the audiences who hear them.
The 2006 JAMA paper I cited is emblematic of the confusion of merit and value. Physicians commitment to altruism . . . scientific integrity and an absence of bias in medical decision-making, the authors assert, now regularly come up against financial conflicts of interest. Scientific integrity, however, is not about absence of bias. It is about experiments designed to falsify, not confirm, hypotheses. The conflict-of-interest literature ignores this basic epistemological point and is itself rife with confirmation bias because it begins with the assumption that medicine should promote activities that conflict-of-interest researchers find meritorious. A value-centric perspective would set aside ideological concerns over supposed conflicts of interest and instead focus on whether industry-supported research is producing better health outcomes for patients.
The JAMA paper reveals another ideology-laden framing bias that plagues anti-industry activists: the celebration of altruism in medicine. Those who would banish (or mostly banish) industry from medicine do not appreciate that avarice is no longer the deadliest of sins, that capitalism is the engine of prosperity and value.
In its pre-scientific era, medicine did more harm than good, so these early physicians sought elevated stature by positioning themselves as priests and aristocrats. The rank of the physician was therefore a product of character, not results. The residua of this desperate grasp for status, an anachronism now that medicine can deliver value, accounts for the energy behind the emergence of conflict-of-interest literature and the reticence of physicians and academics to shed the illusion that money doesnt matter to them.
In addition to ideology, academic politics gets in the way of industry financing in medicine. Most physicians, including academics in health centers, are independent contractors struggling to survive, competing for scarce resources. They cannot sustain a practice, fund a research project, publish a paper, or secure investment for innovation without the support of their bosses.
The need for these crumbs makes the rank and file dependent upon leaders. The dependence means that the leaders have little accountability and can make unsupported, misleading, or false claims in an effort to protect their own authority, which may be undermined when even unwarranted allegations of financial corruption invite political and media opprobrium.
Basing policies on ethics has been an excuse to avoid the hard scholarly work of assessing risks and benefits in the highly complex activities of health care.
Despite their ideological and political commitments, policymakers still pay lip service to the need for collaboration with industry. But collaboration is a difficult and long-term task, and the policymaking effort is always directed toward a short-term goal: to lower the temperature raised by the reverberation between critics, politicians, prosecutors, tort lawyers, and the press. Rather than promote valuable collaboration, the policies mollify activists. Yet even the most draconian protocols are light years from where the most extreme activists want them, and the hysteria will not remit unless persons of credibility resist.
One route to bad policy collects so-called experts on conflict of interest. These are policy entrepreneurs or ethicists who make their living or have staked their prestige on promoting the dangers of industry relationships and on strict regulation of them. The policies they write are predictable.
Another approach relies on senior faculty, even some with industry experience, to write conflict-of-interest guidelines. Unfortunately, these individuals have many responsibilities, have not read and digested the conflict-of-interest literature, and dont have the time or interest to address the nuances of industry relationships. Above all, they protect their own interests. The process defaults to imitation of other policies and to appeasement.
Corporate money in health care is not an ethics problem. It is a matter of nuanced practicality. Basing policies on ethics has been an excuse to avoid the hard scholarly work of assessing risks and benefits in the highly complex and granular activities operating in health care.
The key issue is value for patients. Value is as I defined it: not abstract virtue. The public wants value, not virtue. The public gets value, and the public gets it about value. Contrary to the allegations, patients do not have a trust problem. Surveys have shown no decline in physician esteem; two-thirds of respondents believe researchers should profit from their discoveries; and an overwhelming majority of patients enrolled in clinical trials have no concerns about the financial relationships of the physicians conducting the research.
The policies now in place are based on subjective reflection and misleading and even false ideas imposed and enforced without accountability or feedback. They persist because my most prominent superstar academic colleagues who have gained mightily from their industry relationships remain silent. They fear the wrath of a medical culture that frowns unnecessarily upon the notion that physicians work for profitsometimes extraordinary profit, when they provide extraordinary benefits.
Anti-industry critics advance utopian schemes, grounded in sacred or secular religion. They propose that the government and academic institutions tap nonexistent monies to reward physicians and academics only with salaries fixed by anointed authorities, and that physicians and academics work for abstract ends defined by those same authorities. These are interesting classroom exercises, but ultimately are incompatible with an imperfect reality that has nonetheless delivered great advances in health care.
Thomas P. Stossel is American Cancer Society Professor of Medicine at Harvard Medical School, Senior Physician at Brigham and Womens Hospital, and co-founder of Critical Biologics Corporation.