September 11, 2008
Big Pharma and Health Care: Unsolvable Conflict of Interests Between Private Enterprise and Public Health/Commentary/Author’s Response
By Brezis, Mayer Belmaker, R H
Mayer Brezis, MD, MPH Center for Clinical Quality & Safety, Hadassah Medical Center & School of Public Health, The Hebrew University of Jerusalem, IsraelAbstract: A landmark paper on Game Theory showed that individual maximization of profit necessarily endangers the public good, and since the problem has no technical solution, "it requires a fundamental extension in morality" (1). We propose here that public health, as a public good, now emerges as a grave example of this problem. Recent events and reports increasingly suggest misalignment between the interests of the pharmaceutical industry and those of public health. Johnson & Johnson illegally and effectively promoted Propulsid off-label for children despite internal company documents raising safety concerns. Death in drug trial has been described as a "trade secret." On Vioxx, Topol wrote: "Sadly, it is clear that Merck's commercial interest exceeded its concern about the drug's toxicity" (2). More and more concerns are raised by scholars and major journal editors about the type and the quality of published evidence, often biased towards efficacy of new products. The industry, funding over 80% of trials, sets up a research agenda guided more by marketing than by clinical considerations. Smart statistical and epidemiological tactics help obtain the desired results. Budget for marketing is by far greater than for research. Massive advertising to physicians and to the public gets increasingly sophisticated: ghost writing, professional guidelines, targeting of consumer groups and manipulating media for disease mongering. Pervasive lobbying and political ties limit the independence of regulatory bodies. Obligation to shareholders overriding public health considerations is not unique to the pharmaceutical industry. The chemical, tobacco and food industries share similar tactics: proclaiming doubts about safety issues, buying researchers, infiltrating universities, boards, media and legislative agencies. By contrast, powerful and cheap health promoting activities, poorly supported by industry because they are too cheap and not patented, are markedly underutilized: technologies for changing behavior (e.g., cardiac rehabilitation), palliative care and use of old, effective and safe drugs - all could benefit from industry's tools of marketing and quality. As those most affected are the sick, the poor and the least educated, free market successes appear to pose unsolvable challenges to social justice in public health.
Social Justice in Health Care
In recent consensus papers on modem physicians' ethics, social justice appears as a fundamental novel principle, not present in the classical Hippocratic Oath. The Ethics Manual, published by the American College of Physicians, declares (3): "Physicians (...) should promote justice in the health care system and should base allocations on medical need, efficacy, cost-effectiveness and proper distribution of benefits and burdens in society."
While the pharmaceutical industry has significantly contributed to therapeutic advances, in recent years the exponential rising cost for medicine (4) is not necessarily translated into far better health care or into increase in longevity. Investing this money in health promotion, clinical quality and safety, or palliative care could in fact be more cost-effective.
Given the profit motive that underlies industry's activities, a general question that emerges is: How solvable is the conflict of interests between private enterprise and public health? Adam Smith, who presciently viewed the modern free-market, claimed: "by pursuing his own interest he frequently promotes that of the society..." (5). More recently, however, a landmark paper on Game Theory described "the Tragedy of the Commons" and showed that individual maximization of profit necessarily endangers the public good, and since the problem has no technical solution, "it requires a fundamental extension in morality" (1). Health care is a public good that induces market failure as it differs from other merchandise such as cars or food: in health care, there is a large information gap between consumers and vendors, there are many uncertainties related to diagnosis or outcomes, the system is complicated by insurance and indirect payments that allow gaming, and, finally, when life itself is at stake, framing of issues is often more emotional than rational. For these reasons, the health market is greatly susceptible to corruption, as recently reviewed by the organization Transparency International (6). We propose here that public health now emerges as a grave example of conflict of interests with private enterprise.
Safety Concerns Dwarfed by Industry
Recent events and reports increasingly suggest misalignment between the interests of the pharmaceutical industry and those of public health. Attempts by companies to minimize, deny or hide adverse effects by COX-2 inhibitors have shed an important light on what may be in fact common tactics (7-9). In 2000, JAMA published the information that Celebrex when used for six months is associated with lower incidence of gastro-intestinal complications. In the unreported second six months of the study, nearly all serious complications occurred in people taking Celebrex, negating the original conclusion (7). The JAMA editor said: "I am disheartened to hear that they had those data at the time that they submitted [the manuscript] to us... We are functioning on a level of trust that was, perhaps, broken" (7).
This year, similar concerns have been expressed by the editors of The New England Journal of Medicine, commenting that an original article on Vioxx did not accurately represent the safety data available to the authors. Since 2001 Merck has been denying the risk of myocardial infarction, spending around $160 million/year in advertising Vioxx. Merck sent a note to its sales representatives, ordering: "Do not initiate discussions on [this topic]" and instructing them to show doctors asking about Vioxx and myocardial infarction a pamphlet prepared by its marketing department, indicating that Vioxx was associated with reduced cardiovascular mortality (10). Topol concluded: "Sadly, it is clear to me that Mercks commercial interest (...) exceeded its concern about the drug's (...) toxicity" (2). When fighting a pharmaceutical giant, it may not be wise to be so outspoken: While Merck's CEO received over $30 million in bonus and stock options in 2004, Topol was recently fired from his position at the Cleveland Clinic.
According to an inquiry by the U.S. Senate, Johnson & Johnson had illegally promoted for children the "off-label" use of Propulsid (a medication for gastro-esophageal reflux - now removed from the market because it may induce serious heart arrhythmias) at a time when internal company documents were already raising safety concerns (11). After dozens had died taking the medicine, sales continued to surpass $1 billion per year with continued promotion of use in infants: 20% in neonatal intensive care units were given it, while physicians were never made aware of concerns about a drug which had never been approved by the FDA for this age group.
During a trial on duloxetine (an SSRI tested for use in stress incontinence), a young volunteer with no depression committed suicide. The FDA investigation of the death was reported as a "trade secret" (protected even under the Freedom of Information Act). After medical investigative journalist Jeanne Lenzer published the story (12), the FDA revealed that the rate of suicide attempts with duloxetine in trials of stress urinary incontinence was double that of a placebo. Lenzer concluded: "The use of trade-secret laws to conceal deaths and serious side effects linked to drugs has the obvious flaw of putting profits before public health." It appears as if the interests behind attempts to clear safety issues are by far stronger than the data. Altogether, the events reported above suggest, at the very least, that the systems in place provide the industry more incentives to hide safety concerns than to genuinely protect public health.
Evidence B(i)ased Medicine
More and more concerns are raised by scholars and major journal editors about the type and quality of published evidence, often biased towards efficacy of new products as systematic publication bias favors the industry: Repeated analyses have shown that trials funded by the industry are 2 to 5 times more likely to recommend an experimental drug compared with trials funded by nonprofit organizations (13-15).
The industry, funding over 80% of trials, now sets up most of the research agenda, which is guided more by marketing than by clinical considerations. For instance, very few if any new antibiotic agents are produced to treat short-term bacterial infections induced by emerging resistant bugs, while dozens of antiviral agents are available (or in the pipeline) to treat chronic viral infections, such as hepatitis B, because profits from life-long therapy are by far higher than those from one- or two-week courses of treatment. The money of the industry buys the best statisticians and epidemiologists, who can design the smartest ways to help obtain results desired, as recently reviewed by Richard Smith, former editor of The British Medical Journal (16). A systematic review indicates that randomized trials stopped early (for possible benefit) often show implausibly large treatment effects and recommends viewing with skepticism the conclusions of such trials because they may be biased (17). Cost-effectiveness analyses also show consistent bias favoring the industry in studies funded by for- profit institutions (18). In view of all these problems, how can a genuine reader draw the correct conclusions from reading the literature? Evidence-based medicine has given way to evidence- biased medicine (13). As a result, not surprisingly, many examples exist of therapeutic failures for drugs believed for years to be safe and effective, only later to be shown as dangerous and/or ineffective (19-21). Indeed, it often takes years to achieve a balanced view about widely used medications, often to realize with disappointment their poor performance, such as what happened to hormone replacement therapies, weight-reduction agents, antidepressant and antipsychotic drugs (19-22). In fact, as Deyo and Patrick reflect, our obsession with medical advances bears a high cost of false promises by the industry (21).
Former editors of The New England Journal of Medicine, Kassirer and Angell, have each described in great detail (23,24) how the drug companies have become powerful and sophisticated in the way they deceive us with frequent ghost writing in scientific journals (legitimizing claims from the industry under cover of paid experts) and pervasive involvement in the formulation of professional guidelines (25). The proportion of the budget spent on marketing is estimated at 36%, by far higher than the 11% devoted to research - allowing massive advertising to physicians at a yearly cost of $5.5 billion in the U.S. alone, an amount greater than the entire budget of medical schools to train physicians in the U.S.A. (10). Harvard Professor Arnold Relman, also former Chief Editor at The New England Journal of Medicine, says the drug corporations have changed their role from "developing the drugs that society really needs to trying to extract as much money as they possibly can from the health care system" (26). It is interesting to note that these judgements by former editors of prestigious medical journals were made public after they had left their positions at editorial boards, suggesting that they perhaps felt not so free to speak while still working at their journals. Since revenue from advertising is substantial (27), companies may refuse to advertise in journals that publish opinions critical of the drug industry (28).
Advertising Drugs and Selling Sickness
Public advertising gets increasingly powerful using aggressive direct-to-consumer marketing, payments to celebrities for appearing on TV shows and telling about their illnesses and cures, and sophisticated targeting of consumer groups that will then effectively lobby insurers and regulators for the industry's causes (23, 24).
A most remarkable tactic for expanding drug markets is "disease mongering," i.e., trying to convince essentially well people that they are sick by medicalization of trivial conditions: for instance, defining abdominal discomfort as irritable bowel syndrome or normal aging as menopause and osteoporosis, inducing people to believe they need treatment (29). Psychosocial conditions are especially susceptible to framing by experts as medical conditions: attention deficit hyperactivity disorder (ADHD), depression, social anxiety disorder, sexual dysfunction, and premenstrual "dysphoria." Pharmaceutical companies use the Internet to access teachers and to influence their brokerage role to increase ADHD diagnosis and Ritalin usage (30). For concerned parents, a suggested response by Novartis to teachers is: "Make it clear to them that it is important for them - and their child - to understand and follow the doctor s medical advice about medication and other therapies for ADHD. ADHD is a serious condition that may require the child to be on medication and undergo counseling for a long duration" (30). Big Pharma has taken an aggressive marketing interest in sex, using public relations, advertising, and a variety of tactics to create a sense of widespread sexual inadequacy and interest in drug treatments, both for women and men. People are often enchanted by simple solutions, fitting a cultural overinvestment in biological explanations, to bypass sexual embarrassment, ignorance, and anxiety (31). Pfizer hired a former baseball player as spokesman, teaming up with Sports Illustrated magazine, in an attempt to convince men to enhance normal sexual function with Viagra, as a lifestyle drug. Because of public pressure on insurers, an important concern is that paying for lifestyle drugs will limit resources for other health care (32). A collection of articles on disease mongering and how to counteract the problem was recently published in the 2006 April issue of Public Library of Science Medicine.
Similar Problems in Psychiatry
Mental health presents remarkable examples of economic pressures hampering the process of discovering true evidence on drugs and cautious use in practice. For instance, the safety problems and the limited efficacy of atypical antipsychotic agents are only recently becoming realized, many years after their original approval by the FDA (22, 33). Professor David Healy lost a job offer by the University of Toronto after he publicly raised the question of whether Prozac might increase the risk of suicide (34). Prior to Healy's lecture, Eli Lilly, manufacturer of Prozac, had donated 1.5 million dollars to this institution, which apparently became worried about the risk to further financial inflows from pharmaceutical company sources (35). As recently discussed by Healy (36), the approval of SSRIs suggests that current regulatory practice overstates the benefits and underestimates the risks of drugs. A review showing excess of suicides on SSRIs suggests prior manipulation of data (stepping-up suicides on placebo by inclusion of the wash-out period) to support a null hypothesis (37). An observational study denying an increase in risk of suicide after starting treatment with newer antidepressant drugs (38) allows an inverse conclusion: peak incidence of suicides before discharge could derive from those having just started the medication. A letter we wrote to the Editor discussing this issue did not get published for "lack of space" - space for advertising antidepressants being perhaps more lucrative (27, 28). Manipulation of data by the industry has biased the estimates for suicide risk while rigid interpretation of confidence intervals for each trial has delayed our appreciation of the potential danger of suicide as a class effect of SSRIs (36). Recent meta-analyses now suggest that these medications may in fact have no clinically meaningful advantage over placebos and that antidepressants have not been convincingly shown to affect the long-term outcome of depression (39). Since antidepressants have become society's main response to distress expectations may be false, and the guidelines for their appropriate use need to be reconsidered (39). In a recent discussion, Moncrieff proposes that the pharmaceutical industry has popularized the idea of "imbalances in brain chemicals," a message that has helped neoliberal economic policies increase consumption of drugs rather than finding political responses to social challenges and maladjustments (40).
Pervasive Lobbying and Political Ties
Conflicts of interest among senior scientists are pervasive in prominent agencies such as the National Institutes of Health, and many top paid scientists fail to report their financial deals with pharmaceutical companies. The implications are far-reaching and, although solutions have been proposed, to clear concerns about the integrity of the biomedical research enterprise will be daunting (41). An example of a potentially corrupting influence of industry on policy was recently seen when an PDA's advisory panel recommended Vioxx and other COX-2 inhibitors to continue to be sold, despite their clear cardiovascular toxicity, only with black-box warnings: The decision was swung by 10 of the 17 panelists who had ties with drugs' manufacturers (42).
Constant pressure of the industry on regulatory agencies also manifests as relentless attempts by manufacturers to extend patents, in one way or another, such as modification of the formulation or isomer production of the same molecule - allowing AstraZeneca to renew an expiring patent on Prilosec to a new one for Nexium, despite the two drugs having essentially the same active molecule: omeprazole (26). With FDA approval Pfizer will study a new promising HDL-cholesterol raising drug only in combination with the company's best-selling Lipitor, although antitrust laws would normally prohibit a manufacturer from offering a drug only when "bundled" with another one of its products (43).
President Bush's federal action agenda for mental health has met criticism because it promotes unproven screening examinations and a controversial treatment algorithm with use of newer, more expensive antidepressants and antipsychotic drugs (44). Alien Jones, an employee of the Pennsylvania Office of the Inspector General, revealed that key officials with influence over the medication plan in his state received money from companies with a stake in this medication algorithm (45). As it turns out, one of them, Eli Lilly, has multiple ties to the Bush administration: George Bush Sr. was a member of Lilly's board of directors and Bush Jr. appointed Lillys chief executive officer to a seat on the Homeland security Council. Lilly made $1.6m in political contributions in 2000 - 82% of which went to Bush and the Republican Party (44).
While traditionally opposed to regulation, in recent times, more and more corporations wish to be closely involved in the enacting of new laws, in a clever strategy of "if you can't beat them, join them." Indeed, Congressmen and Senators are constantly exposed to lobby from the industry, including from drug companies, which have become deeply involved in the formulation of new regulations, to make sure to protect the manufacturers' interests, such as those related to patents. This area is worth research to examine to what extent public or private interest is being protected in this game. At this point, it appears as if political ties with the industry limit the independence of regulatory bodies, such as the FDA, and jeopardize critical democratic functions designed to protect public health. Shared Strategy with Other Industries
The problematic stratagems described above are by no means unique to the pharmaceutical industry and have been used by others, such as the tobacco, the chemical, and the food industries: proclaiming doubts about safety issues, buying researchers, infiltrating universities, boards, media and legislative agencies (46 - 48). An executive of a tobacco company described the slogan for his industry's disinformation campaign: "doubt is our product," i.e., to promote the impression of considerable uncertainty and scientific controversy about the damage from smoking. A remarkable review in The Scientific American describes how, in recent years, many other industries have adopted a similar strategy (47): Corporations have mounted campaigns to question the adverse health effects of exposure to beryllium, lead, mercury, vinyl chloride and a long list of other toxic chemicals and medications. In fact, Congress and President Bush's administration have encouraged such tactics by making it easier for private groups to challenge government-funded research (47). An enlightening book entitled "Deceit and Denial" details the attempts by the chemical and lead industries to mislead Americans about the dangers that their products present to workers, to consumers and to the public at large (49). The authors, scholars of public health and history, carefully describe the public relations campaigns and the manipulations of regulatory bodies by the lead and the polyvinyl industries to market their products even after they had realized their potential risks. For instance, advertising lead to paint walls, toys and furniture continued even after a wealth of information was available that children were at risk for serious brain damage and death from ingesting this poison (49). Similarly, the food and drink industries, like the tobacco industry, lobby officials, co-opt experts and expand sales by marketing to children, members of minority groups, and people in developing countries (48).
In all these instances, the obligations to shareholders appear to override considerations about public health. But corporate CEOs are not the ones likely to pay the price of environmental pollution or poor health care. Those most affected are the sick, the poor and the least educated, and, therefore, free market successes appear to pose unsolvable challenges to social justice in public health. Thus, the model of the Game Theory mentioned earlier, the Tragedy of the Commons (1), does not accurately depict the problem, since the price of individual maximization of profit does not affect public health uniformly: it falls predominantly on the have-nots.
By contrast to the overuse of marginally effective emerging health technologies, major, powerful and cheap health promoting activities, poorly supported by industry because they are too cheap and therefore not patented, are markedly underutilized: technologies for changing behavior (e.g., cardiac rehabilitation), palliative care and use of old, effective and safe drugs - all could benefit from industry's tools of marketing and quality.
Many scholars have proposed technical solutions to the problems posed by the pharmaceutical industry (19-21, 23, 24, 26). Voluntary ethical guidelines have been shown to fail (50). A reform in drug approval should include that manufacturers should produce, not evaluate new drugs and that the comparison should be with existing drugs and not with placebo. The independence of regulatory bodies should be strengthened and patent protection should be reduced. The industry should be excluded from medical education and direct-to- consumer advertising totally banned. Evaluation of new treatments needs a radical, in-depth revolution (51).
The industry will oppose these changes, and with its current power and ties to political forces, a significant move towards correct directions is unlikely. Awareness, research and public education about the problem are necessary to foment sufficient political will for change. Transparency about potential risk of products should be an integral part of an ethical code of conduct in the industry. On the other hand, public health activists should learn from the industry the valuable techniques of marketing and quality control to better achieve an effective and just utilization of limited health care resources (52).
I'm grateful to Prof. Hillel Halkin and to Ms. Jeanne Lenzer for their constructive criticism of this manuscript.
1. Hardin G. The tragedy of the commons. Science 1968; 162:1243- 1248.
2. Topol EJ. Failing the public health - rofecoxib, Merck, and the FDA. N Engl J Med 2004;351:1707-1709.
3. Snyder L, Leffler C. Ethics manual (5th edition). Ann Intern Med 2005;142:560-582.
4. Editorial. Prescription drug expenditures rising - too fast? CMAJ 2005;172:1261, 1263.
5. Smith A. An inquiry into the nature and causes of the wealth of nations. Dublin: Whitestone, 1776.
6. Transparency International. Corruption and Health. 2006 http:/ /www.transparency.org/publications/gcr/download_gcr.
7. Abramson J, Starfield B. The effect of conflict of interest on biomedical research and clinical practice guidelines: Can we trust the evidence in evidence-based medicine? J Am Board Fam Pract 2005;18:414-418.
8. Curfman GD, Morrissey S, Drazen JM. Expression of concern reaffirmed. N Engl J Med 2006;354:1193.
9. Juni P, Reichenbach S, Egger M. COX 2 inhibitors, traditional NSAIDs, and the heart. BMJ 2005;330:1342-1343.
10. Waxman HA. The lessons of Vioxx - drug safety and sales. N Engl J Med 2005;352:2576-2578.
11. Saul S. Senators ask drug giant to explain grants to doctors. New York Times, July 6, 2005; C p. 3.
12. Lenzer J. Drug Secrets. What the FDA isn't telling. Slate. Sept. 27, 2005 http://www.slate.com/id/2126918/.
13. Melander H, Ahlqvist-Rastad J, Meijer G, Beermann B. Evidence b(i)ased medicine - selective reporting from studies sponsored by pharmaceutical industry: Review of studies in new drug applications. BMJ 2003;326: 1171-1173.
14. Djulbegovic B, Lacevic M, Cantor A, Fields KK, Bennett CL, Adams JR, Kuderer NM, Lyman GH. The uncertainty principle and industry-sponsored research. Lancet 2000;356:635-638.
15. Als-Nielsen B, Chen W, Gluud C, Kjaergard LL. Association of funding and conclusions in randomized drug trials: A reflection of treatment effect or adverse events? JAMA 2003;290:921-928.
16. Smith R. Medical journals are an extension of the marketing arm of pharmaceutical companies. Public Library of Science Medicine 2005;2:e138.
17. Montori VM, Devereaux PJ, Adhikari NK, Burns KE, Eggert CH, Briel M, Lacchetti C, Leung TW, Darling E, Bryant DM, Bucher HC, Schunemann HJ, Meade MO, Cook DJ, Erwin PJ, Sood A, Sood R, Lo B, Thompson CA, Zhou Q, Mills E, Guyatt GH. Randomized trials stopped early for benefit: A systematic review. JAMA 2005;294:2203-2209.
18. Bell CM, Urbach DR, Ray JG, Bayoumi A, Rosen AB, Greenberg D, Neumann PJ. Bias in published cost effectiveness studies: Systematic review. BMJ 2006;332: 699-703.
19. Abramson J. Overdosed America: The broken promise of American medicine. New York: Harper Collins, 2004.
20. Avorn J. Powerful medicines: The benefits, risks, and costs of prescription drugs. New York: Knopf, 2004.
21. Deyo RA, Patrick DL. Hope or hype: The obsession with medical advances and the high cost of false promises. New York: AMACOM, American Management Association, 2005.
22. Lieberman JA, Stroup TS, McEvoy JP, Swartz MS, Rosenheck RA, Perkins DO, Keefe RS, Davis SM, Davis CE, Lebowitz BD, Severe J, Hsiao JK. Effectiveness of antipsychotic drugs in patients with chronic schizophrenia. N Engl J Med 2005;353:1209-1223.
23. Angell M. The truth about the drug companies: How they deceive us and what to do about it. New York: Random House, 2004.
24. Kassirer JP. On the take: How America's complicity with big business can endanger your health. New York: Oxford University, 2005.
25. Choudhry NK, Stelfox HT, Detsky AS. Relationships between authors of clinical practice guidelines and the pharmaceutical industry. JAMA 2002;287:612-617.
26. Law J. Big Pharma. Exposing the global healthcare agenda. New York: Carroll & Graf, 2006. Public Health/Politics.
27. Friedman LS, Richter ED. Excessive and disproportionate advertising in peer-reviewed journals. Int J Occup Environ Health 2006;12:59-64.
28. Lexchin J, Light DW. Commercial influence and the content of medical journals. BMJ 2006;332:1444-1447.
29. Moynihan R, Cassels A. Selling sickness: How the world's biggest pharmaceutical companies are turning us all into patients. New York, NY: Nation Books, 2005.
30. Phillips CB. Medicine goes to school: Teachers as sickness brokers for ADHD. Public Library of Science Medicine 2006;3:e182.
31. Tiefer L. Female sexual dysfunction: A case study of disease mongering and activist resistance. Public Library of Science Medicine 2006;3:el78.
32. Lexchin J. Bigger and better: How Pfizer redefined erectile dysfunction. Public Library of Science Medicine 2006;3:e132.
33. Lamberti JS, Olson D, Crilly JF, Olivares T, Williams GC, Tu X, Tang W, Wiener K, Dvorin S, Dietz MB. Prevalence of the metabolic syndrome among patients receiving clozapine. Am J Psychiatry 2006;163:1273-1276.
34. Schafer A. Biomedical conflicts of interest: A defence of the sequestration thesis - learning from the cases of Nancy Olivieri and David Healy. J Med Ethics 2004;30: 8-24. 35. Healy D. Good science or good business? Hastings Cent Rep 2000;30:19-22.
36. Healy D. Did regulators fail over selective serotonin reuptake inhibitors? BMJ 2006;333:92-95.
37. Healy D, Whitaker C. Antidepressants and suicide: Risk- benefit conundrums. J Psychiatry Neurosci 2003; 28:331-337.
38. Simon GE, Savarino J, Operskalski B, Wang PS. Suicide risk during antidepressant treatment. Am J Psychiatry 2006;163:41-47.
39. Moncrieff J, Kirsch I. Efficacy of antidepressants in adults. BMJ 2005;331:155-157.
40. Moncrieff J. Psychiatric drug promotion and the politics of neoliberalism. Br J Psychiatry 2006;188:301-302.
41. Steinbrook R. Standards of ethics at the National Institutes of Health. N Engl J Med 2005;352:1290-1292.
42. Okie S. Raising the safety bar - the FDA's coxib meeting. N Engl J Med 2005;352:1283-1285.
43. Avorn J. Torcetrapib and atorvastatin - should marketing drive the research agenda? N Engl J Med 2005; 352:2573-2576.
44. Lenzer J. Bush plans to screen whole US population for mental illness. BMJ 2004;328:1458.
45. Lenzer J. Whistleblower removed from job for talking to the press. BMJ 2004;328:1153.
46. Cohen JE, Ashley MJ, Ferrence R, Brewster JM, Goldstein AO. Institutional addiction to tobacco. Tob Control 1999;8:70-74.
47. Michaels D. Doubt is their product. Sci Am 2005;292: 96-101.
48. Nestle M. Food politics: How the food industry influences nutrition and health. Berkeley: University of California, 2002. California Studies in Food and Culture: 3.
49. Markowitz GE, Rosner D. Deceit and denial: The deadly politics of industrial pollution. Berkeley: University of California, 2002.
50. Chalmers I. From optimism to disillusion about commitment to transparency in the medico-industrial complex. J R Soc Med 2006;99:337-341.
51. Evans I, Thornton H, Chalmers I. Testing treatments. Better research for better healthcare. London: British Library, 2006.
52. Siegel M, Doner L. Marketing public health: Strategies to promote social change. Gaithersburg, Maryland: Aspen, 1998.
Address for Correspondence: Prof. Mayer Brezis, Center for Clinical Quality & Safety, Box 53, The Hebrew University Hadassah Medical Center, POB 12000, Jerusalem 91120, Israel. E-mail: [email protected]
RH Belmaker, MD
Ben-Gurion University, Israel
The very title of this paper, "!Insolvable Conflict of Interests," presupposes the conclusion that the conflict of interests between big pharma and health care are unsolvable. No one can argue that the pharmaceutical industry and medicine have differing interests but I think it could be clearly argued that they also have many interests in common in addition to those which diverge. The author mentions game theory and models of divergent interests, but he does not take into account that not every game is a zero sum game. The famous and useful book, called "Getting to Yes" (R. Fisher, B. M. Patton and W. L. Ury, Boston: Houghton Mifflin, 1992), points out that even a chess game is not entirely a zero sum game since both players have a common interest that no outsider should overturn the chess table. Clearly, medicine and the pharmaceutical industry have a common interest that no one overturn the table in our common desire to find new treatments for our patients.
It is brave of Dr. Brezis to write the article he did which points out many examples of industry exploitation, overcharging, monopolization and data management. However, he does not point out the many accomplishments of the pharmaceutical industry which are clear in all areas of medicine and in psychiatry in particular. Moreover, he does not even hint at an alternative to the private pharmaceutical industry that exists in the West today. It is well known, but cannot be stated often enough, that in the 70 years of its socialist existence the Soviet Union did not develop a single new drug. There is a well known concept in economics, fittingly described in the book, "The European Economy Since 1945" (B. Eichengreen, Princeton, N.J.: Princeton University Press, 2007), that it is much easier to be a follower economy and adopt technologies that have been developed by a "leader" economy than to be an innovator economy. Given the existence of pharmaceutical treatments of mental illness it would probably be possible, as Dr. Brezis suggests, to develop a cheaper and more egalitarian system of pharmaceutical delivery. The question is whether we would reduce our chances for innovation in the future.
Dr. Brezis's manuscript is brave but I dare to say that it is not balanced. While we in the Jewish tradition cling to our faith in the Messianic era, all of my life experience teaches me that there are no really perfect solutions to any human problem: It is unwise and even dangerous to suggest revolutions; rather we should tinker with the system, continually to try to improve it. The present system needs tinkering to reduce conflict of interest between physicians as independent prescribers and pharmaceutical companies as profit seeking promoters; it needs tinkering to guarantee access by the public to all data available on pharmaceutical company trials; it needs tinkering to assure that new compounds be compared to existing compounds rather than placebo in most cases; it needs tinkering to ensure that there is adequate public non-profit funding for orphan compounds and new uses for already existing generic compounds; and it needs tinkering to ensure that major journals publish only scientific articles for which individual physicians are responsible and that they have seen all the data and analyzed it independently. However, we should never let our campaign to make these changes be hijacked in a way that would endanger the existence of a free, competitive and innovative pharmaceutical industry.
With regard to disease mongering, Dr. Brezis gives some examples and there is no question that the discovery of a new medicine can sometimes tremendously increase medical and public awareness of the problem for which the medicine is profitable to use. All of us know some examples of great overuse of medicines in situations where non- pharmaceutical treatment might also be effective. However, I am uncomfortable with the Puritan thread in Dr. Brezis's attack on the use of sildenafil, which he calls a lifestyle drug. Pain has been part of dying for most of human history but no physician would call use of pain relief medicine a life-style intervention. The reduction in erectile function with age may be a normal part of aging in the sense that it occurs in the majority of men with aging, but as a clinician I have seen many couples' marital relations deepened and even saved by appropriate use of sildenafil. There is certainly a place for a polemic like Dr. Breziss article which can awaken public opinion. However, the danger is always that when both sides sling mud the cause of balanced truth will be the loser.
No conflict of interests declared.
Address for Correspondence: E-mail: [email protected]
Mayer Brezis, MD, MPH
Harvard University (sabbatical)
I put in front of ourselves a mirror shared by a growing and impressive list of academic leaders. We may not like what we see in the mirror - denial is a natural but unconstructive defense mechanism. As I see here from my sabbatical at Harvard, the problems posed by the intricate relationship between healthcare and private enterprise are viewed as so grave that they are discussed time and again in many academic forums. Every week, a new book or articles in leading scientific journals shed light on unfathomed depths of issues that need better understanding and better solutions. Over the last year alone, a real deluge of publications has flooded the public agenda with the very problems Dr. Belmaker thinks I exaggerate (1-13). I will quote here from just a few for our readers.
At the American Academy of Arts and Science in Boston, near Harvard Square and the beautiful autumn foliage of New England, I heard former Chief Editor of The New England Journal of Medicine, Professor A. Relman, present his new book, "A second Opinion" (1). Relman analyzes in detail the "medical-industrial complex," showing that for-profit organizations regularly underperform not-for-profit ones. He calls for a return to values: "Medical professionalism cannot survive in the current commercialized health care market. The continued privatization of health care and the continued prevalence and intrusion of market forces in the practice of medicine will not only bankrupt the health care system, but also will inevitably undermine the ethical foundations of medical practice and dissolve the moral precepts that have historically defined the medical profession" (2). He strongly disapproved of the Dean of Harvard Medical School for accepting big money from the pharmaceutical industry. When I met with Relman earlier in his Harvard office, he explained to me his response to Belmaker's type of denial: "People tell me that I'm unrealistic but I answer them: You are not realistic - the system is about to collapse."
Patients trust physicians because they believe in our integrity, our impartial knowledge and our accurate representation of their interests. Healthcare is enduring a severe crisis of trust because patients accurately sense that the medico-industrial complex now derails us from our primary mission of caring (3). Money cannot buy trust anymore than it can buy love. The debate about what is legitimate for physicians has now become public in U.S. media.
In a recent interview for The Boston Globe, Dr. Daniel Cariat, a prominent psychiatrist trained at Massachusetts General Hospital (MGH), said: "Our field as a whole is progressively being purchased lock, stock, and barrel by the drug companies: this includes the diagnoses, the treatment guidelines, and the national meetings (...). Perhaps worst of all, drug companies have come to sponsor so much of continuing medical education that the companies can set much of the agenda"(14). He criticizes MGH for accepting millions of dollars of drug company money to sponsor its continuing psychiatry courses: "Instead of getting educated about psychotherapy, about how to better manage our practices, about epidemiology and the public health concerns of underserved populations, what we're getting is lecture after lecture about how to diagnose depression and use antidepressants to treat it; how to diagnose insomnia and use sleeping pills to treat it; how to diagnose bipolar disorder and use mood stabilizers to treat it." Kassirer, another former Chief Editor of The New England Journal of Medicine, agrees that psychiatry has gone too far (14). "Drug whore" is the expression Cariat uses to describe what he was when he promoted Effexor for money from the drug company: "I realized that I was being paid to say good things about drugs, regardless of what my actual opinions were." He recently described in moving details his experience as "Doctor Drug Representative" in The New York Times (4). The pervasive and troubling buying of psychiatry by the drug industry has been described by other senior psychiatrists (15) and by Professor Healy in his book: Let them eat Prozac (16). Communism developed no new drugs - including none of the infamous ones: Thalidomide, Elixir Sulfanilamide, Triparanol, Fen-phen, Rezulin or Vioxx (see 5 if you have forgotten). Yet, remarkable innovations were made before and outside capitalism. Polio, smallpox and anti-rabies vaccines as well as penicillin were discovered before the current patent rage and race to stock markets. SaIk is quoted to have said, "Who owns my polio vaccine? The people! Could you patent the sun?" Nobelists Fleming and Florey did not patent penicillin because they felt "it should belong to humanity." Banting sold the patent for insulin for $1 so it could be made affordable. Industry was useful for refining these inventions but it is denigrating to imply that great human minds cannot innovate without financial incentives.
Pharmaceutical superpowers threaten free competition no less than communism. Many signs indicate the drug market is neither free nor competitive: wide disparities and secrecy in pricing (under true free competition, prices are known and tend to converge), oligopoly (few firms control many markets), fierce suppression of generic competitors, widespread fraud and criminal behavior (5). Patents are interference with the freemarket that limit freedom when it is felt that left alone competition insufficiently rewards innovation. But now the industry often views patents as rights, exerting political and financial power to impose them on governments: Doing so cannot be claimed as upholding the free market (5).
Recent discussions at scientific meetings here make me think conflicts between industry and public health run far deeper than I had imagined. Leading scholars argue that corporations have gained too much influence on society, in a way that threatens democracy, common goods and public health (17-21). Like healthcare industries, tobacco, food, oil and chemical corporations strategically manipulate research, pay experts, control universities, media and regulatory agencies - a dangerous process called Supercapitalism by Robert Reich, Professor of Public Policy at Berkeley (18). Ensuing poverty predicts poor health in a stronger way than genes, smoking or lack of exercise (see documentary series "Unnatural Causes: Is Inequality Making Us Sick?" to be aired in 2008 ). As Israeli politicians also ought to recognize, public spending on education, health and welfare is compatible with economic growth, say leading economists (23). An authentic Jewish value, promotion of social justice is now recognized as a fundamental principle in the new physician charter (24).
Many scholars agree on the gravity of problems and the need for fundamental strategy shift (5). Others, often with ties to the drug industry, so deeply believe in free-market ideology that they fear alternative standpoints as Utopian or revolutionary (and even if not formally defined by journal editors as conflicts of interests when more than 2-5 years have elapsed, such past ties abound: I had some with a radiocontrast company over 10 years ago and so did Dr. Belmaker with Eli Lilly ). As Professor Brodys brilliant analysis shows, "tinkering with the system" has failed over four decades and the false hope "now it will succeed" is part of a pervasive psychology of denial (5). Medicine is deeply "hooked" to industry by gifts and rewards, while physicians deny influence on their judgement despite extensive contrary evidence (5). We need to choose between academic and financial freedom - we cannot have both, said a Yale Professor of Political Science in a recent lecture at Harvard (26). Financial dependence of institutions, like an addiction (27), comes at the price of academic independence and with denial as psychiatrists know, addiction is a disease of denial (5). In fact, denial (and not the recognition of gravity of issues) may set the stage to a revolution - if and when repressed social forces become unleashed.
Pfizer successfully spent hundreds of millions of dollars in advertising Viagra to young men who don't need it (unlike in Dr. Belmaker's example): the largest increase in its use was between age 18 and 45, without etiologic reasons for needing it (28). As effective as Viagra, exercise improves sexual dysfunction (29), as does alleviating anxiety and depression, as recently reviewed by a Harvard psychiatrist (30). Wouldn't it be better had society spent the money to promote physical activity?
Physicians, public health professionals and policy makers should learn how public health conflicts with corporate-controlled market state. Pharmaceutical industries should do what they are best at: producing drugs, not evaluating them and not educating us or the public about them. We, physicians, should keep our academic and professional integrity clean to deserve the trust of patients and society.
No conflict of interests declared.
1. Relman AS. A second opinion: Rescuing America's health care. A plan for universal coverage serving patients over profit. New York: The Century Foundation & PublicAffairs, 2007.
2. Relman AS. Medical professionalism in a commercialized health care market. JAMA 2007;298:2668-2670.
3. Shore DA. The trust crisis in healthcare : Causes, consequences, and cures. New York: Oxford University 2007.
4. Dr. Drug Rep. By Daniel Cariat. The New York Times. November 25, 2007. http://www.nytimes.com/ 2007/11/25/magazine/25memoir- t.html?_r= 1&oref=slogin (Accessed December 26, 2007).
5. Brody H. Hooked: Ethics, the medical profession, and the pharmaceutical industry. Rowman & Littlefield, U.K.: Plymouth, 2007.
6. Callahan D, Wasunna AA. Medicine and the market: Equity vs. choice. Baltimore, MD: The John Hopkins University, 2007
7. Campbell EG. Doctors and drug companies - scrutinizing influential relationships. N Engl J Med 2007; 357:1796-1797.
8. Faunce TA. Who owns our health? Medical professionalism, law and leadership beyond the age of the market state. Sydney, Australia: University of New South Wales, 2007.
9. Campbell EG, Weissman JS, Ehringhaus S, Rao SR, Moy B, Feibelmann S, et al. Institutional Academic Industry Relationships. JAMA. 2007;298:1779-1786.
10. Yank V, Rennie D, Bero LA. Financial ties and concordance between results and conclusions in meta-analyses: retrospective cohort study. BMJ 2007;335:1202-1205.
11. Wells DA, Ross JS, Detsky AS. What is different about the market for health care? JAMA 2007;298:2785-2787.
12. Grill M. Kranke Geschafte: wie die Pharmaindustrie uns manipuliert. Reinbek: Rowohlt: Aufl, 2007.
13. Brownlee S. Overtreated : Why too much medicine is making us sicker and poorer. New York: Bloomsbury, 2007.
14. 'No' to drug money. Dr. Daniel J. Cariat wants to limit corporate sway over psychiatry. By Carey Goldberg. The Boston Globe. May 7, 2007. http://www. boston.com/news/globe/health_science/ articles/ 2007/05/07/no_to_drug_money/?page=1 (Accessed December 26, 2007).
15. Torrey EF. The going rate on shrinks: Big Pharma & the buying of psychiatry. American Prospect 2002;15:15-16.
16. Healy D. Let them eat Prozac: The unhealthy relationship between the pharmaceutical industry and depression. New York: New York University, 2004.
17. Wiist WH. Public health and the anticorporate movement: Rationale and recommendations. Am J Public Health 2006; 96: 1370- 1375.
18. Reich RB. Supercapitalism: The transformation of business, democracy and everyday life. New York: Knopf, 2007.
19. Glasbeek H. Wealth by stealth: Corporate law, corporate crime, and the perversion of democracy. Toronto: Between the Lines, 2003.
20. Chernomas R, Hudson I. Social murder. Winnipeg, Manitoba: Arbeiter Ring, 2007.
21. Michaels D. Doubt is their product. How industry assault on science threatens your health. New York : Oxford University, 2008.
22. Adelman L. Unnatural causes: Is inequality making us sick? Prev Chronic Dis 2007; 4:4.
23. Lindert PH. Growing public : Social spending and economic growth since the eighteenth century. Cambridge, U.K., New York: Cambridge University, 2004.
24. ABIM, ACP-ASIM and the European Federation of internal medicine. Medical professionalism in the new millennium: A physician charter. Ann Intern Med 2002;136:243-246.
25. Dossenbach MRK, Beuzen JN, Avnon M, Belmaker RH, Elizur A, Mark M, Munitz H, Schneidman M, Shoshani D, Kratky P. The effectiveness of olanzapine in treatment-refractory schizophrenia when patients are nonresponsive to or unable to tolerate clozapine. Clinical Therapeutics 2000;22:1021-1034.
26. Marmor TR. Why is health care so difficult to reform? Seventeenth Henry Hardy Bioethics Lecture. Beth Israel Deaconess Medical Center & Harvard Medical School. December 20th, 2007. 27. Cohen JE, Ashley MJ, Ferrence R, Brewster JM, Goldstein AO. Institutional addiction to tobacco. Tob Control 1999;8:70-74.
28. Lexchin J. Bigger and better: How Pfizer redefined erectile dysfunction. Public Library of Science Medicine 2006;3:e132.
29. Esposito K, Giugliano F, Di Palo C, Giugliano G, Marfella R, D'Andrea F, D'Armiento M, Giugliano D. Effect of lifestyle changes on erectile dysfunction in obese men: A randomized controlled trial. JAMA 2004;291:2978-2984.
30. Ratey JJ, Hagerman E. Spark: The revolutionary new science of exercise and the brain. 1st ed. New York: Little, Brown, 2008.
Address for Correspondence: E-mail: [email protected]
Copyright Gefen Publishing House Ltd. 2008
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