Leaders of research ethics organizations have made placebo-controlled trials illegal whenever placebo groups would not receive currently existing treatment for their ailment, slowing down research for cheaper and more effective treatments. In this essay, I argue that placebo-controlled trials (PCTs) are both morally and legally permissible whenever they provide care that is better than the local standard of care. Contrary to what the anti-PCT often put forth, I argue that researchers conducting PCTs are not exploiting other developing nations, or subjects from these nations, when they conduct their research there. I then show how these researchers are also not especially legally required to provide treatment to their placebo-group subjects. I present some of the benefits of such research to the placebo groups as well and consider the moral impermissibility of making such research illegal.

In this essay, I will address the issue of placebo-controlled trials (PCTs) in research experiments. Research Ethics leaders around the globe have denounced PCTs in developing countries as being exploitative, leading to their illegalization around the globe. This illegalization has not only slowed down research for cheaper and more effective treatment, but has also withheld the partial health benefits that would be bestowed on the experimental subjects who do participate. I argue that PCTs are morally permissible when they provide care that is better than the local standard of care. I do this by first showing that PCTs are not exploitative, and that even if PCTs were morally impermissible, this would not necessarily establish them as being legally impermissible.

In a 2010 study (Temel et al., 2010), 151 patients with newly diagnosed metastatic non-small-cell lung cancer were randomly placed into one of two treatment groups. In one group, patients received early palliative care integrated with standard oncological care. In the other, patients received only standard oncological care. The results of the study showed that the patients who underwent the early palliative care had a higher quality of life and survived about 2.5 months longer than those who did not undergo this care. It seems that the researchers’ refusal to give early palliative care to about 75 patients led to a lower quality of life and an earlier death for them. Could what the researchers have done be considered unethical?

It might seem so at first, but once we understand that, up to that point, there was not much evidence supporting the idea that early palliative care was indeed effective, we can refrain from claiming that the researchers conducted an unethical experiment. The afore-mentioned example shows that, if there is not sufficient evidence supporting one treatment group over another, it would not be unethical for researchers to place subjects into said groups.  In fact, this is the commonly held ethical principle called equipoise, which states, “Prior to conducting the trial, researchers must have no good evidence for thinking that one treatment (in the experimental arm) is better or worse than the other treatment (in the control arm)”. However, would the inverse be true as well?

Some argue that, if there is sufficient evidence that one treatment group is more effective than another, it would be unethical for researchers to place patients in the less effective group. For example, the Food and Drug Administration (FDA) has refused to let researchers conduct placebo-controlled trials of surfactants for the idiopathic respiratory distress syndrome in the United States because there are  “available approved surfactants that are the standard of care” (Charatan). The surfactant drug would save lives of infants while the placebo would not. To refuse to give the surfactant drug and to give the placebo instead would constitute knowingly letting infants die from idiopathic respiratory distress syndrome, where they would have otherwise received the standard of care: the life-saving surfactant drug.  It seems that in this case, it is not difficult to agree with the FDA’s decision to refuse such placebo-controlled trials in the U.S. However, the researchers wanted to conduct this trial in Bolivia, in which the standard of care consisted of no life-saving surfactant drug at all. Would it still be unethical to conduct this PCT? This is the question that this paper will explore. It is important to note that pharmaceutical companies and research organizations favor placebo-controlled trials because they are cheaper and are argued to be scientifically more informative than active-controlled trials or historical comparisons. That is why the researchers would rather have a placebo group instead of a different treatment group.

If we accept that the Bolivians have no claim towards the benefits of the research, then it follows that it is still unclear how the researchers are exploiting their subjects by taking an unfair advantage of the Bolivians.

If the researchers do not conduct the PCT, no Bolivian patients would receive treatment. However, if the researchers do conduct the PCT, at least some patients – those in the treatment group – would receive what might potentially be treatment. Moreover, there might also be some benefits for the placebo group, like the possibility of partially effective placebo effect and the potential benefits that could come from the presence of professional medical personnel. Despite the fact that the outcome of the PCT would be better than the outcome of no PCT at all, many still object to conducting the PCT because it would seem exploitative of Bolivians.

This objection is based on two premises: first, that this PCT is exploitative, and second, that exploitative actions are immoral. I will accept the second premise as true and only focus on the first. If it can be shown that this PCT is not exploitative, then there would be no need to object to the second premise.

It might be thought that the PCT is exploitative because it is taking unfair advantage of Bolivians, whose standard of care is below that of developed countries, to conduct research, which would be illegal in developed countries. Let us consider another case:

George is a businessman living in the US. He owns a small business that sells quality home telephones with cords. Lately however, he has not been able to sell much due to the flourishing of cordless home phones and cell phones. He decides to move his business to Bolivia (or some other underdeveloped country) in order to sell his phones there at the same price. In Bolivia, cell phones and cordless home phones have not yet made their way into the mainstream market.

It does not seem that what George is doing is exploitative. It can be said that George is taking advantage of the slower market in Bolivia in order to sell his phones, but he is not treating them any worse than anyone else. Going back to the PCT case, we might also say that the researchers are simply taking advantage of the lower standard of care in Bolivia. They are not treating them any worse than they would be treating subjects in the United States (because they would have done the same experiment there if the standard of care in the US was the same as that in Bolivia). In this way we can distinguish between taking unfair advantage of people and taking advantage of people’s unfair, or unfortunate, circumstances. What George and the PCT researchers are doing could be considered taking advantage of the unfair circumstances of people, but it could not be considered taking an unfair advantage. Neither George nor the researchers caused the unfortunate circumstances of the Bolivians (slow market and low standard of care).

If we define exploitation as to refer to those actions that take unfair advantage of others, then PCT would not be considered exploitative for the reasons just mentioned. Now, one might respond to this by stating that taking advantage of one’s unfair circumstances is unfair in itself. One might present an example in which a doctor overcharges for a necessary life-sustaining procedure, or in which a company underpays its employees simply because the employees live in an area with minimal job opportunities. These cases might be considered examples of taking an unfair advantage of one’s unfair circumstances because the doctor ought to gain less money than he is asking for and the company ought to pay more money than they are paying their employees. However, these cases are not completely analogous to the PCT case. When comparing what one ought to gain from the transaction, it is not so clear that the Bolivians ought to receive the best treatment. Maybe in a more general theory of the distribution of wealth or health resources, the Bolivians ought to receive the best treatment. However, this responsibility would not solely be that of these specific researchers, but also that of the governments and leaders who have any sort of control over the economy and/or health resources. If we say that, in the transaction between the Bolivians and the PCT researchers, the Bolivians do not have any right to receive the best treatment from them, then we cannot conclude that the PCT researchers are taking an unfair advantage of the Bolivians. In the case of the overcharging doctor and underpaying company, fairness is lost when what one ought to gain/lose is not gained/lost. In the PCT case, there would need to be evidence for something that the Bolivians ought to gain that the researchers are not giving for one to claim that they are exploiting the Bolivians.

At this point, one might say that the Bolivians ought to gain the benefits of the research. In other words, this research must be intended to discover some way to treat some disease that inflicts Bolivians, or to treat them at a cheaper rate. If the research is conducted by foreign researchers to benefit foreign patients, then it could be said that the researchers are taking an unfair advantage of the Bolivians. One might even add that the individual participating in the experiment is not necessarily gaining the benefits of the research. After possibly 300 deaths resulting from the placebo group (or resulting from sickness that was not cured for the placebo group, but that could have been cured by a different treatment), even if some cure for a disease in Bolivia is discovered as a result of the research, the participants in the placebo group will obviously not be receiving that treatment as they would already have passed away. This would suggest that the researchers are taking unfair advantage of the Bolivians because the research subjects themselves ought to benefit from the experiments being conducted on them, yet are not.

However, it is not necessarily true that the PCT subjects are not benefiting from the research. Although they might die before some cure is discovered, participating in the research and taking a placebo is better than the standard of care in that area of the world. Even if the research is intended for foreign patients, the Bolivian research subjects will still possibly benefit from participation. This, however, does not respond to the claim that the Bolivians, in general, ought to receive the benefits of the research. Let us return to the case of George and his corded telephone business. George intends to benefit himself, and possibly his family, by earning a living through selling corded phones in Bolivia. Surely, the specific persons that buy a phone from George will have some benefit of having a corded home telephone. However, it does not seem to be the case that the Bolivians, in general, ought to receive the benefits of George’s business. George is simply making a living for him and his family. Those who buy phones from him are individually opting to choose to buy a corded home phone for themselves.  Any other Bolivian who wants a cordless phone or a cell phone cannot put demands on George that he give, sell, or make available those products to them simply on the basis that the market in Bolivia is slower than the one in the U.S. Likewise, in the PCT case, the researchers could simply be trying to discover some cure for themselves or for patients within their own nation. It does not seem to be the case that the Bolivians, in general, ought to benefit as a result of the ventures of these researchers. The specific Bolivians who decide to be participants in the research are individually consenting to receive at least placebo care, which is better than the Bolivian standard of care, namely no treatment at all for idiopathic respiratory distress syndrome. If we accept that the Bolivians have no claim towards the benefits of the research, then it follows that it is still unclear how the researchers are exploiting their subjects by taking an unfair advantage of the Bolivians.

The conclusion that the researchers are not unethical in conducting a PCT on Bolivians is however not held by some of the leaders of research ethics. The 1962 Declaration of Helsinki of the World Medical Association states that, “[I]n any medical study, every patient—including those of a control group, if any—should be assured of the best proven diagnostic and therapeutic method”. Furthermore, the International Ethical Guidelines for Biomedical Research Involving Human Subjects stated that the ethical standards applied in a study “should be no less exacting than they would be” for research in the sponsoring country itself. To many, the use of PCTs in developing countries seems to be ethically indefensible because it elicits imagery of hypocrisy: the researchers are conducting research abroad that would be illegal at home. We can lessen this unethical imagery by looking at a more specific, individual case:

Arnold’s sister has just been diagnosed with a newly discovered fatal cancer. There is currently no cure for this malady. Arnold, a researcher, figures out that if fruit A can fill an empty stomach over a one-month period, then fruit A can cure this disease. To test this, Arnold needs to conduct an experiment in which one group of subjects eat fruit A with water for a month, while the other subjects eat fruit B with water for the same period of time. Fruit B is exactly like fruit A except that it lacks the healing properties in Fruit A. However, he cannot test this fruit in the United States because it would be unethical to have research subjects live on only fruit A or fruit B in the United States – Fruits A and B lack most essential nutrients, rendering those, who purely consume those fruits for 30 days, in a drastically malnourished state. However, in severely underdeveloped country B, hunger is rampant and the death rate is high due to lack of food. Arnold decides to go to country B and conduct the research. He would give fruit A and water to 100 starving participants, and would give fruit B and water to another 100 participants.

It does not seem that the imagery of hypocritical researchers arises in this example. Arnold’s research would be illegal at home but not in country B. However, not only is he conducting this research in order to save his dying sister, but he is also providing water and food to all participants. Given the standard of hunger in the area, these participants would not have had something to eat that is as healthy and as abundant as fruits A and B. In fact, we can even justifiably add to the example that the placebo participants who received fruit B lived longer than their relatives who did not participate in the experiment. In this case, it would seem morally impermissible to prohibit Arnold from conducting his research abroad. A PCT is not much different from this case. Those in the placebo group benefit, given the low standard of care in their country. Even though the research is not intended for those who are research subjects, the research still seems to be morally permissible. It does not seem to be the case that Arnold elicits imagery of hypocrisy either.

Surely one might say that this is not always the case with PCTs. Sometimes the researchers are not attempting to discover a cure, but are looking for cheaper ways to find a cure. Arnold would, in this situation, not be trying to save his sister, but would be trying to save money. This response seems to ignore the moral benefit of cheaper medicine. Cheaper medicine is more accessible, especially for those in underdeveloped countries. If we view Arnold as a researcher who is trying to find a cure that is affordable for the diseased poor, he would no longer elicit images of hypocrisy.

One case is often given to suggest that it is still morally impermissible to conduct a PCT: a man is walking down the street when he spots a house on fire that is not his own. In a heroic act of courage, the man runs inside to save whomever he could find. He spots a crying baby and a parrot. The man picks up the parrot and leaves the baby in the burning house.

This example suggests that, although the man might have been a very moral person for risking his life to save whomever was inside the house, leaving the stranger baby inside the fire is immoral. The analogy shows that, although the researchers might be giving some subjects treatment, allowing the placebo subjects to not receive the best available treatment would be immoral. However, in the baby/parrot case, there is only one baby in one house on fire, while in the PCT case, there could be millions of individuals in need of a specific treatment. We should expect the heroic man to save the baby once he is in the house already, but we would not expect him to save every baby in the house if there were, for instance, eight babies. One might respond and say that the researchers are responsible for those patients who are research subjects. This response is predicated on the premise that the moral obligation to help another person gets stronger as the difficulty imposed by helping gets lesser. A popular example that highlights this premise is the example of the baby drowning in a pond: a man wearing a suit is walking next to a pond when he spots a random baby drowning in the pond. It seems that the man is morally obligated to save that baby, even though it probably will get his suit wet. However, it seems that another man who is also wearing a suit, but living in another country, is less morally obligated to save the drowning baby if he somehow knew that the baby was drowning. The proximity to the baby, or the ease by which one can save the baby, seems to affect the strength of the moral obligation to help. In the case with the baby/parrot, the man, once inside the house, seems to be morally obligated to save the baby if it is within his capability to carry the baby. However, if there were eight babies, we might say that the man is morally obligated to save as many babies as he can carry, but not necessarily all of them due to the difficulty of carrying so many babies at the same time. Let us look back at the PCT case:

The previous example would suggest that the researchers have a stronger moral duty to provide the best treatment for their subjects because it is not too difficult for the researchers to do so. However, a disanalogy remains in this case as well. Surely we can assume that it would not be too relatively cumbersome for the researchers to give the best treatment to their subjects. However, the ease by which they could aid their subjects is not that much more than the ease by which they could aid random patients who are not subjects in their experiment. To shed some light on this response, let us return to the pond case:

Suppose, in an obviously hypothetical scenario, that there were thousands or tens of thousands of babies drowning all at the same time. We might say that a man is obligated to save a drowning baby in a pond right next to him. However, if there was a pond just a tiny bit further from the man, that also had a drowning baby, it would seem difficult to say that the man is more morally obligated to save the baby closest to him than the one slightly further. If the two ponds were a mile apart, and the man was a few yards from one pond, then we might say that the man is much more morally obligated to save the closer baby. Likewise, the same can be said in the baby/parrot case. If there was another baby in the room just further down within the burning house, we would not say that the man is more morally obligated to save the closer baby. Returning to the PCT case, we might say the same for the relative difficulty in assisting research subjects and non-research subjects. Surely one might say that the researchers would not have much difficulty in giving the best treatment to their subjects, but also that it wouldn’t be that much more difficult for them to give the best treatment to other patients in, say, the hospital from which they acquired subjects. This argument suggests that the researchers would not be more morally obligated to aid their research subjects than their non-research subjects.

An expected response would be that the researchers are still obligated to give the best treatment to some subjects. This is true. However, simply because the researchers are in close physical proximity to the sick patients does not mean that they are any more obligated to provide the best treatment to them than an individual who can easily contribute to their treatment through donation via Internet. There would be no reason to especially obligate the researchers to treat nearby subjects or non-subject patients. In the same way that it would not be illegal for a vacationer from a developed country in an underdeveloped country to pay the expenses for treatment of random patients in the local area, it should not be illegal for researchers in the underdeveloped country to refuse to pay for the best treatment of subjects or non-subjects. Surely it would be moral and supererogatory for the researchers to donate some of their private wealth to fund the cost of the best available treatment, but it would not be legally required of them to do so. Some might say that the researchers are morally obligated to provide the best treatment and that anyone sitting at home with the ability to easily donate online is also morally obligated to provide the best treatment. This, however, is a different topic of discussion that does not address the issue of whether PCTs are especially morally impermissible.

Furthermore, even if PCTs were morally impermissible, this would not establish that they should be illegal. It would be difficult to claim that individuals who desire to be subjects of experiments should be prevented from being so out of some sort of paternalistic care for those individuals by the government (given that being a subject will personally benefit the individual).

In the same way that it would not be illegal for a vacationer from a developed country in an underdeveloped country to pay the expenses for treatment of random patients in the local area, it should not be illegal for researchers in the underdeveloped country to refuse to pay for the best treatment of subjects or non-subjects.

There seems to be a fear that if this argument were to go through, citizens of underdeveloped countries would somehow be abused or extensively exploited. This would give the green light for many experiments that would otherwise be illegal in developed countries to be done in underdeveloped countries. However, this argument seems to ignore the previous arguments. What have been argued thus far is that PCTs are not exploitative and that researchers are no more obligated to provide treatment to their experimental subjects than they would be obligated to provide treatment to other locals. No harm would be done if these experiments were to occur like wildfire. In fact, there would be the potential of much more benefit. If PCTs are given the green light, then we should expect many (who become subjects) to receive some sort of minimal quality of care, and we would expect discoveries of treatments that could benefit the sick in both developed and underdeveloped countries.

 

References

Charatan, Fred. “Surfactant Trial in Latin American Infants Criticised.” BMJ : British Medical Journal. BMJ, n.d. Web.

Frick, Johann D. CHV 333/PHI 333: Bioethics: Clinical and Population-Level: Seminar 12, March 4: Standards of Care and Exploitation in Clinical Trials in the Developing World. Notes.

“International Ethical Guidelines for Biomedical Research Involving Human Subjects.” Council for International Organizations of Medical Sciences. Web.

Temel et al. Early Palliative Care for Patients with Metastatic Non-Small-Cell Lung Cancer. The New England Journal of Medicine, August 19, 2010.

“WORLD MEDICAL ASSOCIATION DECLARATION OF HELSINKI: Ethical Principles for Medical Research Involving Human Subjects.” Journal of Obstetrics and Gynaecology Research 27.2 (2001): Xiii-Xv. Web.