Bioterrorist? Bane of “Big Pharma”? Angel of equity? Industry gadfly? Unrealistic idealist? I have no doubt that some pharmaceutical industry representatives would paint Marcia Angell, MD, former editor-in-chief of The New England Journal of Medicine and author of The Truth About the Drug Companies: How They Deceive Us and What to Do About It as well as “The Body Hunters,” a review of The Constant Gardener,(1) in the most unflattering terms.
Others, whether they have a bone to pick with the way the billion-dollar pharmaceutical industry does business, a legitimate grievance, or simply buy Angell’s arguments, likely see her as an expert fighting the good fight. Closer to the middle of the spectrum, some might see her as well-intentioned but beholden to idealism or naïve to the convoluted interconnections between government and industry. Indeed, the pharmaceutical industry would likely much prefer that observers or interested parties scrutinize an avowed critic of their practices than their practices themselves.
The use of incendiary epithets may certainly serve to divert attention, as absurd as the first admittedly anecdotal one was. No one – or no entity – is beyond reproach or critical analysis, though. And the purpose here isn’t critical evaluation of the messenger but of the implications of the message. That is, if Angell’s comprehensive denunciations of the pharmaceutical industry are accurate, and I believe they are, what actions might be pursued to improve global health and support the critical role that drugs play throughout the world?
My purpose here is not to demonize the pharmaceutical industry; indeed, I don’t think that’s Angell’s goal either. She is arguing for reasonable, ethical provision of goods and services. The pharmaceutical industry has a key role to play. But who is responsible when the industry becomes a starring rather than supporting player? And what, if any, steps can be taken to ensure that drugs are distributed in at least a semblance of an equitable manner? How do we proceed, in other words, to ensure the broader application of ethical standards in terms of the critical role that pharmaceutical companies play in global health?
There are multiple players involved in global health and it behooves all involved to question and understand the motives of each. The primary focus here is the pharmaceutical industry, but I will briefly address some other players as well.
Pharmaceutical Companies: Special Corporations?
Angell joins John Le Carré, various authors in The Washington Post’s “The Body Hunter” series, and Sonia Shah (author of The Body Hunters, which covers similar terrain) in leveling various damning charges at “Big Pharma.”(1) But is it surprising that pharmaceutical corporations exploit loopholes in domestic or international law or, simply, people in the pursuit of maximizing profits? Corporations themselves exist for one primary purpose: to earn as much money as possible for their shareholders. To that end, corporations are committed to whatever actions will result in profit optimization. This is an inherently amoral model that paves the way for what many may identify as immoral acts. Money is a major motivator and must be recognized as such when the opportunity to raise a significant amount of it may lie at the heart of particular actions.
The drug companies or their representatives might claim that Angell and, for that matter, Le Carré and Shah have books to peddle and that the Post journalists were simply trying to sell papers. But Le Carré is a long-established writer hardly in need of a cash infusion and likewise, Angell, a distinguished MD, first female editor-in-chief of the esteemed, high-impact New England Journal of Medicine who worked for the journal for 20 years and now teaches at Harvard, hardly needs to make more of a name for herself to make her life more comfortable. Likely, they haven’t substantially added to their income with these works; given the barrage of criticisms leveled at them from pharmaceutical companies and/or their functionaries, their lives have been made more difficult by taking on the drug giants. In other words, avarice might be ruled out as biasing their arguments. Given Shah’s line of work – investigative journalism – the profit motive in her work might be held in check. In all of these cases, though, the authors stand to gain in stature and, perhaps, set themselves up as experts ready to offer commentaries, interviews, and reviews.
But what of the drug companies and the products that they manufacture and sell? Medicine and access to life-saving drugs is considered a right in much of the developed world. As involved as they are in producing such goods, should drug companies operate like prototypical corporations? If so, then their mission is to maximize shareholder profits, with their merchandise – drugs and devices – serving, in a sense, an almost incidental role. Such goals play out in the US in the form of expanding markets by stoking or disseminating the belief that an ever-expanding array of new drugs is needed to live life.
The more chronic a condition appears to be, the more captive the market. That is to say, if pharmaceutical companies can convince a substantial portion of the population that it suffers from fibromyalgia or depression and that long-term courses of drugs are the answer, a guaranteed revenue stream is created and continually reinforced. Why change one’s diet, when one can pop a Prevacid? Why make lifestyle changes when one can take cholesterol-lowering medication, even in one’s 40s? Indeed, while resisting lifestyle changes to lose weight, why not consider an obesity drug to do the hard work?
In seeking newer revenue streams, drug giants have also forged and made normative the notion that natural life-course developments are medical conditions requiring or that might call for medical, or pharmaceutical, intervention. Essentially, phenomena such as pre-menstrual “syndrome,” menopause, andropause, and aging have been characterized as medical conditions (or medicalized). I am not contending that a percentage of the general population (likely smaller than is actually medicating for these “conditions”) does not experience discomfort or other symptoms associated with these life changes, but that such symptoms might be mitigated through dietary and lifestyle changes in line with traditional practices before such “syndromes” became known as disorders. You can also read this article if you truly value your health especially in this phase of your life.
Once a health state is considered a medical condition, new revenue streams are born for the drug suppliers and they work to meet and expand the demand. While Ritalin had been around for a few decades, its use for the newly coined conditions attention deficit disorder (ADD) and attention deficit hyperactivity disorder (ADHD) exploded in the 1990s during the early stages of the direct-to-consumer advertising era in the US. Treatment for depression similarly grew in exponential fashion, with no signs of letting up despite recent evidence suggesting that anti-depressants may not be significantly more effective than placebos.(2) Undoubtedly, despite complex contributing factors to the recent increase in asthma diagnosis and incidence in Barbados, including industrialization and improved awareness and understanding of symptoms, government and practitioner reliance on relationships with drug companies, who wield disproportionate influence, looms as the predominant element in the Caribbean island’s asthma conundrum.(3)
Skepticism regarding pharmaceutical company motives for their wide range of actions is much more warranted than it might be in scrutinizing the motives of its critics.
Photo Credit: Flickr/faungg ; CC2.0
Closing Pandora’s Box
The rules that govern and guide the conduct of clinical research are more stringent in the developed world than in the developing world, and their formation was significantly informed by the evolution of modern bioethics, as represented most frequently by principlism or the four principles approach.(4, 5)
Autonomy may be the most cherished of the principles in the US, but US-based companies may not find it so dear when working abroad. Indeed, some rules are more beneficial to drug companies than others. Put another way, such corporations have the wherewithal to surmount regulatory obstacles when necessary or, given their hefty budgets dedicated to the cause, to lobby their way out of limiting legislative straitjackets. Like impish children testing the waters to see what they can get away with when facing a parent, teacher, or guardian’s rules, drug companies continually push the envelope in search of maximizing profits by reducing costs, increasing revenue, and expanding profit margins.
If this results in exploiting less educated, more malleable populations, and/or even those with copious reasons to be skeptical of foreign interlopers, not to mention their own governments, but no resources or wherewithal to oppose them, it appears irrelevant to multinational corporations.
The US, home of the pharmaceutical behemoth Pfizer, is the only developed country that lacks universal health coverage; it is also one of only two countries (the other is New Zealand) that allows direct-to-consumer marketing of prescription drugs, legal since the late 1970s. Not surprisingly, the pharmaceutical industry sunk significant funding into lobbying efforts for legislation that would permit this sales approach, previously left to the province of doctors.
With Pandora’s box opened, the industry now has carte blanche to plant ideas in consumers’ minds, leading to requests for new prescriptions during medical visits, and drug companies have been amply rewarded. But these corporations still have the US Food and Drug Administration (FDA) and their rules regarding investigational new drugs to abide by and standard developed country protocols to adhere to, with informed consent representing perhaps the most significant one pertaining to conducting clinical trials.
Another regulatory change, in 1980, that has opened a different but similar set of floodgates for American drug companies was the FDA agreement to accept foreign trials as evidence of safety and effectiveness.(1) This has sent US drug companies, which have found increasing difficulty in recruiting enough subjects for clinical trials, to less developed countries, where they can spend less money in less time with less oversight than they would face in the US.(6)
Once such regulatory changes are implemented in any setting, the chances of reverting to a period of stricter regulation are remote and unrealistic and any movement for turning back the clock would seem to be ingenuous or quixotic.
Pharmaceuticals Rush in Where Angels Don’t Fear to Tread
Angell speculated that nearly half of all clinical trials performed now are done so in developing countries. In 1996, Nigeria, the most populous country in Africa, was under siege with an epidemic of bacterial meningitis. Médecins Sans Frontières, known in the US as Doctors Without Borders, had sent up a camp in the northern city of Kano to treat patients. Pfizer decided to set up an adjacent camp after a company employee surfing the Internet while at home in Texas noted the news of the Nigerian epidemic and thought that the stricken African nation would be a suitable setting to test the drugmaker’s potential blockbuster antibiotic Trovan.(6)
The germ of the idea wasn’t altruistic as was the motive of the Nobel Prize-winning Doctors Without Borders, but capitalistic. What ensued might have been predicted. Of the multiple flaws or what would be considered breaches of clinical trial protocol in the US cited by Angell and Stephens, including a falsified, back-dated Nigerian ethics board approval, the absence of a written record of informed consent, the pillar of ethically sound research studies involving human subjects in developed countries, stands out as one of the most glaring. While Pfizer claimed that research subjects orally consented, interviews with parents and doctors painted a very different story.
The juxtaposed encampments, Doctors without Borders and Pfizer, saw diametrically opposed results. The humanitarian organization treated patients with intravenous antibiotics, per protocol, and ultimately immunized over 4 million people (7); the drug company, in and out of the country within a month, tested their oral medication against a lower-than-recommended dose of a comparison drug and was later sued by the families of 30 Nigerian children who died or who suffered seriously from the treatment. The families and Pfizer have since settled out of court.
Little independent oversight and questionable consent certainly characterized Pfizer’s trial in Nigeria and might well describe similar efforts throughout the industry in less developed countries, as regulations and enforcement are lacking. Companies will not offer full disclosure, but simply what is required.
While informed consent among test subjects is a more significant issue, such practices also manifest when a corporation performs oversea trials because of doubt expressed regarding the safety and efficacy of a test drug in the company’s home country. After the FDA refused to permit Maxim Pharmaceuticals Inc., based in California, to test a drug on American subjects with liver disorders, the company conducted a trial in Russia, without informing officials regarding the FDA’s concerns, but abiding by the local rules, the chairman of Maxim defended.(8) Similarly, Pfizer, again, was denied FDA approval of its schizophrenia drug Zeldox without further testing, some of which was later conducted in Bulgaria, without informing officials there of the drug’s FDA status.(9)
Pharmaceutical companies cannot and should not be expected to behave as responsible corporate citizens unless forced by external regulation. They will not regulate themselves beyond indemnity from crippling lawsuits while in their pursuit of the precious financial bottom line. Perhaps the issue of overseas testing is best summed up George J. Annas, head of the health law department at Boston University School of Public Health, “I’d argue you can’t do studies ethically in a country where there is no basic health care.”(9)
Photo Credit: Flickr/Kojach ; CC2.0
How to Proceed
Despite the litany above and varied implications to the contrary, I don’t want to paint pharmaceutical companies as malevolent. They produce vital products to combat infectious and chronic diseases; millions of people have been saved by medications and many more with more innocuous conditions experience needed relief through such products.
In addition, pharmaceutical companies are far from the only players on the global health scene. Nongovernmental organizations of many stripes, governments, regulatory bodies, global financiers and donors, as well as health organizations have critical roles to play. Indeed, it can be easily argued that the top-down approach prompted by a cooperative effort of the World Health Organization, UNICEF, and the US Centers for Disease Control and Prevention, with US and European donors and the Nigerian government was responsible for the underwhelming response to a polio vaccination program in Northern Nigeria in 2005.(10)
Perhaps a different kind of input is necessary.
Regarding pharmaceutical input, one suggestion however unlikely to be implemented, is offered by economist Dean Baker, co-director of the Center for Economic and Policy Research, who suggests that the billion-dollar pharmaceutical industry be assessed much more than the current 5.6% of its profits in corporate taxes, which is a result of various tax breaks and loopholes.(11) Baker’s notion was put forth in reference to increasing revenue from corporate taxation.
In this context, perhaps, in order to ensure that the tax code remains in their favor, a concession might be exacted from the pharmaceutical industry, a veritable corporate community service. That is, legislation could require pharmaceutical companies to donate money and, perhaps more importantly, medications that can be used to treat infectious diseases in the various developing countries in which the drug companies seek to conduct lower-cost, expedited trials among a less educated, impoverished population in an environment with little oversight.
Realistic enforcement of such practices would require great cooperation among executive and legislative branches of government, and health organizations such as the World Health Organization and UNICEF.
More broadly, cooperation might very well be promulgated as a principle of global bioethics. Indeed, invoking the spirit of Hellesten’s sensitivity to the context of local cultures and the role of Paul Farmer’s “pragmatic solidarity,” cooperation or participation must be sought among not just the various governmental, health, and various other humanitarian organizations, as well as prominent health stakeholders such as Marcia Angell and Paul Farmer, but the target populations themselves in seeking practical solutions to issues pertaining to global health. Such participation or input could certainly impact the roles that pharmaceutical companies are permitted to play in health interventions.
It seems unlikely that any one player would arrive at the best solution for tackling a particular global health problem; perhaps they can only be achieved through the participation and cooperation of representatives of all involved parties. We’re all in it together.
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EDITOR’S NOTE: THE OPINIONS EXPRESSED HERE BY IMPAKTER.COM COLUMNISTS ARE THEIR OWN, NOT THOSE OF IMPAKTER.COM.
References
- Angell M. The Body Hunters. The New York Review of Books, Vol. 52, Number 15, October 2005.
- Turner EH, Matthews AM, Linardatos E, Tell RA, Rosenthal R. Selective publication of antidepressant trials and its influence on apparent efficacy. N Engl J Med. 2008 Jan 17;358(3):252-60.
- Whitmarsh I. Biomedical ambivalence: asthma diagnosis, the pharmaceutical, and other contradictions in Barbados. American Ethnologist, 2008;35(1):49-63.
- Hellsten SK. Global bioethics: Utopia or reality? Developing World Bioethics, 2008;8(2):70-81.
- Takala T. What is wrong with global bioethics? On the limitations of the four principles approach. Cambridge Quarterly of Healthcare Ethics, 2001;10:72-7.
- Stephens J. The Body Hunters: Where Profits and Lives Hang in Balance. The Washington Post, Dec. 17, 2000.
- Doctors without Borders website: http://www.doctorswithoutborders.org/aboutus/timeline.cfm?ref=main-menu. Accessed 7/13/11.
- Flaherty MP, Nelson, D, Stephens J. The Body Hunters: Overwhelming the Watchdogs. The Washington Post, Dec. 18, 2000.
- LaFraniere S, Flaherty MP, Stephens J. The Body Hunters: The Dilemma: submit or suffer ‘uninformed consent’ is rising ethic of the drug test boom. The Washington Post, Dec. 19, 2000.
- Renne E. Perspectives on polio and immunization in Northern Nigeria. Social Science & Medicine, 2006;63:1857-69.
- Baker D. The trouble with corporate taxes. The New York Times, April 13, 2011.
