Ethics in medical research can sometimes be a blurry line, with ethical guidelines varying by country, and being far less clear cut than strictly quantitative issues. Such is the case with a study sponsored by the U.S. National Institute for Health, which was conducted in a developing country and is being reviewed for publication by Medical Science Review, a prominent journal that prints cutting edge research on medical issues. The study had stunning results: a simple, short, regimen which promises to cut HIV (Human Immunodeficiency Virus) transmission rates by 80%. While the study was scientifically sound, the morality is questionable, as researchers used a placebo-based control group, rather than either of the other treatments of HIV currently recognized: A long, and a short AZT regimen, which can be an exploitation of the lower economic status of research participants in these countries. The question is whether or not Medical Science Reviewshould publish this study. This paper will explore the ethicality and the moral fraughtness of this experiment, and conclude that, while not identical circumstances, this paper should be published just as other data, such as that obtained during Nazi experimentation, is used. The research should be published, as it is scientifically sound, and the damage done to participants who were ethically mistreated is only worsened by refusing to publish the results of the research. However, a foreword should be published along with it, condemning the unethical research practices.
There are two main ethical concerns which spring from this experiment, given the limited information we have on their research methods. The first being possible exploitation of a developing country and its people as test subjects. The other issue being with the use of a placebo-based control group itself, rather than a previously proven treatment of a long or short AZT regimen.
The first issue is the issue of possible exploitation of populations in developing countries. “The Declaration of Helsinki of the World Health Organization (WHO)…is widely regarded as providing the fundamental guiding principles of research involving human subjects.” (Angell 1) and is a primary source for parsing whether an experiment is ethically treating patients and can help determine if an experiment in a developing country is exploitative. The Declaration of Helsinki states “In research on man [sic], the interest of science and society should never take precedence over considerations related to the wellbeing of the subject,” (Angell 1), which essentially says arguments of an experiment being for a “greater good” or potential benefits to a large number of people does not outweigh a research participants moral rights to care and information. The benefit of the greater good was one way the Tuskegee experiment was justified, that the “study was important (a ‘never-to-be-repeated opportunity,’’ said one physician after penicillin became available)” (Angell 2) and that the results would be “valuable, but it was especially so for people like the subjects” (Angell 2), using an argument of the results leading to a common good to defend the unethical treatment of over 200 poor men of color, many of whom were denied care even after treatment for syphilis (which Tuskegee researched a cure for through deceit of patients) became available.
The Declaration of Helsinki also specifies that “in any medical study, every patient — including those of a control group, if any — should be assured of the best proven diagnostic and therapeutic method” (Angell 1). This part specifically mentions the control group, which in the case of the experiment at hand, was a placebo receiving group. “The Declaration of Helsinki requires control groups to receive the “best” current treatment, not the local one” (Angell 3), the best current treatment globally in this instance what have been a long or short AZT regimen, rather than a placebo for the control group. This is important because “acceptance of this ethical relativism could result in widespread exploitation of vulnerable Third World populations for research programs that could not be carried out in the sponsoring country” (Angell 3). In other words, if we opt for a “local standard of care” model, then researchers will have a scientific and financial interest in maintaining access to populations in which the standard of care is lower than in the United States. Adopting a local standard of care leads to increased possibilities for exploitative practices, allowing for the perpetuation of low-income developing nations and populations without access to quality healthcare, with the defense of researching on them being that a significant number of (significantly wealthier) people will benefit from the medical knowledge, which is the major concern with possible exploitation.
Beyond the issue of exploitation is the inherent moral grey area of using placebo-based control groups, despite being a fairly standard scientifically sound way of researching the effect of a new treatment. Some argue that there is no moral issue with placebo control groups as “some officials and researchers have defended the use of placebo-controlled studies in developing countries by arguing that the subjects are treated at least according to the standard of care in these countries, which consists of unproven regimens or no treatment at all” (Lurie and Wolfe 4). This argument used the local standard of care loophole previously discussed, which has its own issues of exploitative practices which can arise from this viewpoint. However, even though “the citizens of these impoverished countries may indeed have a moral right to a better standard of living…this is almost certainly a claim that will be unredeemed for the foreseeable future” (Crouch and Arras 28). While it can be acknowledged that the local standard of care is not an optimal approach to research in a developing country, in particular instances where the main benefit is to people living in those populations, whatever progress which can be made until inequalities in healthcare can be overcome are better than nothing. Often, the global standard of care is not available to these studied populations, mostly due to economic inequalities. Until those inequalities are overcome “[woman in the] Third World would not receive…treatment anyway, so the investigators are simply observing what would happen…if there were no study” (Angell 2). Finding a new treatment may not be as effective but is better than nothing. As, “a placebo-controlled study is the fastest, most efficient way to obtain unambiguous information that will be of greatest value in the Third World” (Angell 2) and while not the preferred option “the inclusion of placebo controls ‘will result in the most rapid, accurate, and reliable answer to the question of the value of the intervention being studied compared to the local standard of care’” (Angell 2). This is the specific condition in which the research at hand would be considered ethical in its use of a placebo group – when it is used to benefit the population being studied, and not as a cost cutting measure. We are not given the researcher’s motivations however, and so it is unclear if the placebo group was carried out ethically.
However, some researchers take issue with placebo-based control groups for their adoption of the local standard of care in cases such as this and argue that what are termed “equivalency studies” by Lurie and Wolfe be used in their place. Equivalency studies, simply put, use the best-known method of treatment as the control group, rather than a placebo. These researchers “believe that such equivalency studies of alternative antiretroviral regimens will provide even more useful results than placebo-controlled trials, without the deaths of hundreds of newborns that are inevitable if placebo groups are used” (Lurie and Wolfe 3). The issue with equivalency studies is exactly why placebo studies are still a norm in many cases. “This proposed method…would have the undesirable effect of preventing researchers from answering the most meaningful questions that motivated the research in the first place” (Crouch and Arras 29). What is meant here, is that, if the point of the research experiment is to find a treatment which would work and be available in this specific developing country, comparing results to a treatment they have no access to would be pointless, even if placebo trials do wrong by these populations ethically, the economic systems in place have made it impossible to give them the equal healthcare they have a moral right to from the start, so placebo trials are simply working within the confines of the system, even if they are less preferable ethically. A particular condition to ensure placebo trials are not exploitative in nature is that the results will benefit the host country in particular, and that the condition of a placebo group arises from a need to establish a baseline and lack of available treatment, not from attempts to cut costs in developing countries to benefit wealthier populations. Because “even if the organizers were well intentioned, their research may nevertheless violate ethical canons if its positive fruits are not made reasonably available to former research subjects and other inhabitants of the host country” (Crouch and Arras 30).
The argument against the publication of this study rests on the ways it can be viewed as unethical. Without knowing the researcher’s intent to provide care for participants of the study post-experiment, and whether the research is intended to benefit the population the research was conducted in, the question of exploitative practices is highly possible but uncertain, as the motivation and reasoning behind the research methods were not disclosed for this experiment. As examined previously, it is possible to conduct placebo-based research in a developing nation without being explicitly exploitative, as long as the caveats of the Declaration of Helsinki are followed, and the local standard of care is used only to benefit that population itself. If these conditions are not met, the research is unethical, and some may argue should not be published. Arguments against publication might also see allowing the study to be published as showing researcher they can get away with unethical studies which are scientifically sound, because being published is a reward for the bad behavior, a sort of perverse or backwards incentive. Arguments for publication rest on the previously discussed ways these types of experiments can be ethical, or at least, as ethical as possible while operating within the confines of the economic inequalities in place systematically, with one of the goals of research improving healthcare in developing areas to help this gap narrow. Though in this case placebo-based trials are acceptable, a preface explaining why it is reasonable in this instance and precautions taken to limit or prevent exploitative practices should be published with the research, explaining the ultimate goals of helping the developing population at hand, because that it the condition it would take for this experiment to have been ethical or not.
Regardless of whether or not the experiment was exploitative or not, and thus ethical or not, the research should still be published, with a preface detailing all ethical concerns of the experiment. We simply do not know which would apply, as we do not have all the details of how patients were treated or how results are going to be used. There is historical basis for using scientifically sound data with morally questionable background. During World War II, “Nazi scientists performed brutal experiments on Jews and gypsies in the concentration camps” (Wilkerson), and there were “experiments in which the Nazis used hundreds of people to test human reaction to long-term exposure…while they monitored their subjects’ deaths.” (Wilkerson). While these experiments were clearly unethical, the results and data are still used in mainstream science as “it served no purpose to science to ignore data that could help people…The wrongs perpetrated were monstrous; those wrongs are over and done. How could the provenance of the data serve to prohibit their use?” (Wilkerson). This historical basis shows as that, even if the study at hand were proven to be unethical in their choice to use a placebo-based trial, the study should still be published, as the damage which has been done is done, and ignoring the results does not help anyone. The study could still be published, whether or not it was found to be truly unethical.
It is possible to use data that is obtained unethically, because the damage done to people cannot be undone, and using the research does not worsen their suffering. Research methods cannot be ignored, “however hard we might try, we cannot separate the data from the way they were obtained” (Wilkerson), and it is important not to separate the data from its methods, because that allows for complacency and forgetting the past, that is what allows for exploitative practices benefiting a greater good, what leads to looking the other way and allowing another Tuskegee incident, as mentioned earlier in the paper. There is “benign acceptance of Nazi data in modern-day science and the occasional, matter-of-fact reference in contemporary scientific papers. ‘Nazi data…is absorbed without comment into mainstream science,’ Dr. Caplan [director of the Center for Biomedical Ethics at the University of Minnesota] said. ‘That I find disturbing.’” (Wilkerson). It should be disturbing. You should understand where data comes from, and what the cost of it was. “It should be used if the circumstances under which it was conducted are acknowledged” (Wilkerson), meaning that the research at hand could be published, so long as ethical concerns of the study are addressed alongside its publication.
If data obtained from Nazi research can be used ethically, though the research itself was not ethically done, then the same applies in this instance. We do not know the exact conditions of the experiment conducted, and so we cannot know whether the placebo-based control group was used for an ethical or exploitative reason. Whichever is the case, the research should be published by Medical Science Review, as the data is potentially valuable, and the experiment is scientifically sound. However, along with publication, acknowledgement of possible ethical issues of exploitation and the ultimate goals of achieving better local standards of care which justify the use of placebo trials should be published along with the data in the form of a preface or foreword, so that neither ethical issues nor the bigger picture can be forgotten or ignored. Provided the research is proven to have been done ethically, the foreword could detail the conditions under which it is ethical, especially the condition of serving the specific population studied, and working to narrow the healthcare gap between developing and developed countries. If the study is found to be unethical, the study should still be published, but the foreword should describe the ways it was unethical, the conditions which would have made it ethical, and show that the unethicality of the research method is neither ignored nor condoned by the journal.
Angell, Marcia. “The Ethics of Clinical Research in the Third World.” New England Journal of Medicine, vol. 337, no. 12, 1997, pp. 847–849., doi:10.1056/nejm199709183371209.
Crouch, Robert A., and John D. Arras. “AZT Trials and Tribulations.” The Hastings Center Report, vol. 28, no. 6, 1998, p. 26., doi:10.2307/3528266.
Lurie, Peter, and Sidney M. Wolfe. “Unethical Trials of Interventions to Reduce Perinatal Transmission of the Human Immunodeficiency Virus in Developing Countries.” New England Journal of Medicine, vol. 337, no. 12, 1997, pp. 853–856., doi:10.1056/nejm199709183371212.
Wilkerson, Isabel. “Nazi Scientists and Ethics of Today.” The New York Times, The New York Times, 21 May 1989, www.nytimes.com/1989/05/21/us/nazi-scientists-and-ethics-of-today.html.