The recent shifts in the U.S. political climate and the questionable ethics of some in U.S. political leadership have led me, like many others I would imagine, to reflect on my role in politics, as an advocate for change, a representative for how I interpret the concept of justice, and perhaps most importantly, on the professional path I have thus far chosen. I have spent the last thirteen years surrounded by and involved in biomedical research and clinical medicine, experience I hope one day to apply to international development initiatives. Being intimately involved in biomedical research means that I, like my peers in the field, am required to have an in-depth understanding of the ethical responsibilities associated with such inquiry. The U.S. National Institutes of Health (NIH) requires proof of ethics training for funding eligibility, and every facility in which I have worked has had the additional requirement of yearly updates to ensure individual awareness and facility with that guidance. Trainings that fulfill this obligation cover and review everything from the United States Public Health Service Tuskegee Syphilis experiment in which African Americans who contracted that disease between 1932 and 1972 were left untreated, so as to examine its effects, and the wide variety of abhorrent human experiments conducted by the Nazis during World War II that led to the Nuremburg Code and the principle of voluntary consent (U.S. Government Printing Office 1949). Updates also address the Declaration of Human Rights (United Nations General Assembly 1948) and the Helsinki Accords (Riis 2003), the Belmont Report (the report of the National Commission for the Protection of Human Subjects of Biomedical and Behavioral Research released in 1978) with its four key ethical principles for human-related research, and the rights and protections for non-human research animals (National Commission 1978). As violations of the current standards of ethics outlined in the Nuremburg Code, the Belmont Report and elsewhere continue to occur, the vast majority of scientists nonetheless, I believe, daily make every effort to uphold and often surpass those requirements. This essay explores an issue that seems to have escaped today’s medical research ethical safety net and which has been justified on the basis of cost and efficiency. I offer an Aristotelean argument concerning vertical and horizontal justice as both a rebuke to the global healthcare community for permitting this situation and as a means to rectify it.
During the course of a recent literature review, I came across a curious subset of the human rights literature that highlighted the rather appalling idea of a health care and research ‘double standard.’ This scenario arises from a debate concerning whether a ‘placebo’ group is appropriate when testing a new pharmaceutical, combination of pharmaceuticals, or any other medical treatment not yet approved for general use by the Food and Drug Administration in the United States. The currently agreed upon ethical standard, known as clinical equipoise, is that a placebo group is not appropriate if an approved treatment for the same disease or condition exists, and indeed, should a pharmaceutical company attempt to bypass this requirement in a study taking place in the United States, regulatory intervention would be swift and the penalty or cost imposed would be significant. Biomedical researchers are required to provide the existing standard as a baseline of care and determine whether the new treatment constitutes an improvement compared to the old, rather than with respect to nothing at all (a placebo). The ethical principles governing this specific issue are beneficence (efforts to ensure that benefits outweigh risks) and non-maleficence (do no harm). There is no proviso in the Belmont Report or in current regulations for an exception to these principles.
Those who attained majority before the mid-to-late 1990’s may well remember the Pfizer case involving the now withdrawn antibiotic Trovan, a (then) new treatment for meningococcal meningitis. A lawsuit, that was settled out of court for $75 million, asserted Pfizer, in a 1996 meningitis outbreak in Nigeria, gave a reduced dose of the gold standard ceftriaxone to a control group to skew a study concerning the efficacy of Trovan to maximize the likelihood of demonstrating the superior efficacy of the new drug.
Plaintiffs also argued that Pfizer had falsified documents that indicated it had obtained informed consent from patients to participate, as well as general approval from the Nigerian government and their own institutional review board (IRB) for the clinical trial to take place. The study participants were children, and eleven of them died while many others suffered blindness, deafness and paralysis. It remains unclear whether those who acquired chronic conditions did so as a result of their disease (meningitis) or as a result of Trovan’s side effects. The drug was discontinued shortly after its regulatory approval, as evidence emerged of severe liver toxicity associated with its use (Petryna 2006).
When the situation that occasioned the lawsuit came to light, the public outcry was substantial and swift condemnation of Pfizer by the World Bank (WB), World Health Organization (WHO), and the U.S. House of Representatives International Relations Committee followed. Given this history, one can be forgiven for surprise at learning that the NIH and the Centers for Disease Control and Prevention (CDC) both vigorously defended a series of drug trials in 1994 in sixteen African countries that tested a shorter dosing regimen of an anti-retroviral (ARV) drug designed to reduce vertical (mother-to-child) transmission of HIV-1 by using a placebo group, as opposed to the longer-dosing regimen then considered the gold standard treatment for the virus. The rationale? Both funding organizations asserted that a placebo control was acceptable because the trials took place in ‘resource-poor settings’ and that the current standard of care in those countries did not include ARV therapy (Landes 2005). In another surprising example, Nicholson et al. have demonstrated that the WHO actually officially recommended a placebo in lieu of a gold standard treatment for multiple drug resistant tuberculosis (MDR-TB) between 1993-2002, but only for pharmaceutical trials taking place in low-and-middle-income countries (Nicholson 2016). The justifying rationale for this course of action was once again that these nations were ‘resource-poor’ settings and the gold standard of treatment was not, in fact, customary in them. This was so according to WHO officials because insufficient infrastructure and government systems made it too difficult and costly to implement the standard of care enjoyed in the developed world.
This assertion failed to address the question of how individuals who were not treated adequately for MDR-TB affected the global fight against antibiotic resistance in general and whether their lack of care put the rest of the world’s population at greater risk of contracting these diseases. Sadly, there is no shortage of other examples similar to those I have presented here. While the neo-liberal celebration of unfettered free-market enterprise in which development and business currently operate may explain such instances as the Pfizer fiasco, it by no means offers a rationale for why three global flagship healthcare organizations would forego ensuring the basic ethical premise of medical and pharmaceutical research of beneficence that they had a significant hand in establishing.
The argument can be offered, and likewise rejected, that competing values and donor interests play a greater role in determining what projects and studies are funded and how they are designed than does ethics (Gonzalez-Block 2004). However, regardless of donor interest, government relations, resource availability or literally any other proffered rationale, WHO (and NIH and the CDC) purport to uphold specific ethical baselines in their work and are (or should be), therefore, bound by them.
Ethical principles, particularly with regard to how to treat large groups of vulnerable people in medical and health research, are not a new phenomenon. Indeed, they date at least back to Aristotle, whose work provided a simple, rational test for how to apply such standards as non-maleficence, beneficence, justice and autonomy (per the Belmont Report) (Landes 2005 and Culyer 2015). Aristotle offered a two-point evaluative approach to making ethical judgments: vertical and horizontal equity.
Horizontal equity requires that individuals who are similar in relevant ways (i.e., individuals who have MDR-TB, HIV-1 or meningitis, as in the examples outlined above) must be treated in the same way. Vertical equity, meanwhile, demands that people unlike one another in categorical ways must be treated differently in proportion to their differences. One example of how such can be practiced is the use of a sliding scale for fees at a health clinic in which wealthier individuals pay more for their care to help subsidize the treatment of those who cannot afford to pay, or cannot pay as much. Culyer has argued that this idea is not only Aristotelean, but also appears in the works of Karl Marx (Culyer 2015). I find it notable, too, that this ethical premise is taught in very nearly every major world religion.
Paradoxically, however, in the clinical trial examples sketched above, the WHO, NIH and the CDC, rather than interpreting the vertical equity principle as a directive to provide increased aid to those at greatest risk, instead concluded that need constituted a rationale for decreasing assistance and adhering to lower standards of care for such individuals. Notably, this convention was not adopted during a moment of crisis, as with the recent Ebola virus outbreak, during which officials waived the traditional process of approval for potentially viable vaccine candidates in light of the gravity of the situation underway. Even in such a moment, however, the ethical imperative of beneficence was arguably met in the Ebola crisis in that the course adopted was implemented in the view that those receiving a potentially lifesaving vaccine could possibly yield greater benefit than the risk(s) associated with its use, especially when compared to the risk of contracting (and dying from) the virus.
A straightforward course correction for these three major health organizations and any others that have elected to violate ethical principles in developing nation contexts is, quite simply, to apply the standards of care that they employ in trials and projects conducted in high-income countries. It is important to emphasize that such uniformly applied ethical criteria in ‘resource-poor’ settings may be very expensive indeed. However, this stance is firmly based on the human rights claims (as they pertain to human medical research) of the Helsinki Accords and the Belmont Report principles these organizations (and their major Western state sponsors) claim to uphold. This fact suggests that compliance with this approach is a non-negotiable imperative if WHO and other medical research organizations wish to retain any semblance of moral authority and ethical legitimacy.
Culyer, A.J., 2015. Efficiency, equity and equality in health and health care. Center for Health Economics Research Paper Series 120, University of York, pp.1-20.
Gonzalez-Block, M.A., 2004. Health policy and systems research agendas in developing countries. Health Research Policy and Systems, 2(1), p.6.
Landes, M., 2005. Can context justify an ethical double standard for clinical research in developing countries? Globalization and Health, 1(1), p.11.
National Commission for the Protection of Human Subjects of Biome Beha Resea and Ryan, K.J.P., 1978. The Belmont Report: Ethical Principles and Guidelines for the Protection of Human Subjects of Research-the National Commission for the Protection of Human Subjects of Biomedical and Behavioral Research. US Government Printing Office.
Nicholson, T., Admay, C., Shakow, A. and Keshavjee, S., 2016. Double Standards in Global Health: Medicine, Human Rights Law and Multidrug-Resistant TB Treatment Policy. Health and human rights, 18(1), pp.85-102.
Petryna, A., 2006. Globalizing human subjects research. Global pharmaceuticals: Ethics, markets, practices, pp.33-60.
Riis, P., 2003. Thirty years of bioethics: the Helsinki Declaration 1964-2003. New Review of Bioethics, 1(1), pp.15-25.
UN General Assembly, 1948. Universal declaration of human rights. UN General Assembly.
U.S. Government Printing Office, 1949. Permissible Medical Experiments. Trials of War Criminals before the Nuremberg Military Tribunals under Control Council Law No. 10: Nuremberg October 1946–April 1949. U.S. Government Printing Office 2(1), pp. 181-182.
Rebecca Powell-Doherty is a second year MPH student from Charlotte, NC. She previously received her B.S. in Biology from NC State University in 2005 and her PhD in Immunology from UNC Charlotte in 2010. After graduation, she spent some years teaching undergraduate science courses and conducting post-doctoral work in the areas of inflammation and hemorrhagic shock. During her time at Virginia Tech, she has developed an interest in combining a scientific understanding of disease with social applications for improving the lot of those disproportionately affected by it.