Clinical Trials in the Developing World: The Moral

Permissibility of Placebo Control Groups

The fundamental goals of medicine include finding cures, treatments, and preventions for

both individuals and large populations in order to improve the overall health of society. Clinical

trials are integral to meeting these goals, thus thousands of them are conducted worldwide each

year. Although the findings of many clinical trials over the years have contributed to a number of

significant scientific and medical advances from which millions of people have benefitted from,

the early history of clinical trials before regulations were put in place is tainted with ethical

violations that resulted in harm to research subjects. For example, researchers involved in the

infamous Tuskegee experiment that ran from 1932 to 1972 exploited male African American

participants by failing to tell them that they were infected with syphilis, and then failing to treat

them after penicillin was discovered as an effective cure for the disease in the 1940s. In response

to the ethical violations committed in many scientific experiments involving human subjects, the

Declaration of Helsinki was developed by the World Medical Association in 1964 and has

subsequently become widely accepted as the essential document of ethical guidelines for human

research studies.

Despite the development of this document, ethical breaches still frequently occur in

human research studies today. The central moral conflict of these studies is between the

obligation to protect participants from abuse and the goal to benefit these participants and society

as a whole through important scientific research. This moral conflict is especially apparent in the

developing world where research is conducted on vulnerable populations. In this paper, the

conflict between ethics and science will be examined and applied to the controversy of whether
or not it is morally permissible to conduct clinical trials in developing countries if a placebo

control group is used instead of an active control group in which participants receive the current

standard of care for the disease in question. The general consensus is that a trial must use an

active control group rather than a placebo group if an effective treatment for the disease is

available (Angell 1997). More specifically, this issue will be explored using the ongoing clinical

trials conducted in the developing world in the early 1990s that studied the efficacy of a

treatment regimen in preventing the vertical transmission of HIV from mother to fetus. Marcia

Angell, the former editor-in-chief of the New England Journal of Medicine, criticized these trials

because researchers used a placebo control group even though a drug that effectively prevents

vertical transmission was available and widely used in more developed nations (Angell, 1997).

In response, bioethicist Baruch Brody argued that the use of a placebo control group in these

studies was not unjust, and then proposes a different standard by which the ethical rigor of

clinical trials should be judged (Brody, 2002). This paper will examine an essay by Marcia

Angell and another by Baruch Brody and ultimately argue that it is morally permissible to have a

placebo control group despite the availability of a current standard of care under specific

conditions.

In her essay entitled The Ethics of Clinical Research in the Third World, Marcia Angell

claims that an injustice was done to participants in the placebo control group because it violates

the ethical guidelines outlined in the Declaration of Helsinki. According to this document,

Every patient...should be assured of the best proven diagnostic and therapeutic method

(Angell, 1997, p. 1). At the time the trials were being conducted, the drug zidovudine had been

proven to drastically reduce the rate of vertical transmission, and was therefore widely used by

pregnant women who were HIV positive in developed countries. However, the drug was
unavailable in developing nations because of its high cost. In fact, researchers from the

developing world conducted the trials in question to assess the efficacy of a less expensive

treatment regimen that effectively reduces the rate of vertical transmission so that it could be

available in economically disadvantaged nations (Brody, 2002). All but one of the clinical trials

studying the vertical transmission of HIV directly violated this guideline by using a placebo

control group in place of an active control group (Brody, 2002). However, does this violation

mean that the studies were unjust? Supporters of these clinical trials point out the success of

these trials. They yielded valuable findings regarding the appropriate dose, time, and duration

that the treatment regimen should be given to most effectively prevent the transmission of HIV to

the fetus. The trials would not have yielded the same results if an active control group had been

used or if the results from the experimental group were compared with a historical placebo

control group from another study, and thus would not have been as beneficial to society (Brody,

2002). Because of these trials, some developing nations would be given the chance to reduce the

rate of vertical transmission, although the poorest countries would still be unable to afford the

treatment.

Furthermore, other supporters of the trials argue that participants in the placebo control

group were not denied any treatment that they would have received if the trials were not

conducted because zidovudine was not available in developing nations (Brody, 2002).

Therefore, researchers were only observing what would have happened to these participants if

the trial did not exist. On the other hand, Marcia Angell points out that the Declaration of

Helsinki requires that participants in control groups receive the best current treatment rather than

the local one (Angell, 1997). Considering this, participants in these trials should have received

zidovudine despite the fact that it was not unavailable in the countries in which the trials were
conducted. Angell also argues that this justification of a placebo control group is reminiscent of

that provided by defenders of the Tuskegee study (Angell, 1997). In this case, researchers

claimed that they were merely observing what would have happened to the participants without

the study considering that they were too poor to afford the available treatment. This justification

was and still is considered inadequate, leading Angell to claim that it is also inadequate in the

clinical trials in question (Angell, 1997). Baruch Brody also rejects this justification in his essay

entitled Ethical Issues in Clinical Trials in Developing Countries and responds to Angells

argument by proposing a normative standard by which to determine if the use of a placebo

control group is morally permissible. According to Brody, it would not be morally permissible to

use a placebo control group made up of members of a persecuted minority group in a developed

country where effective treatment is available to all except the minority group (Brody, 2002).

Although members of this group would not have had access to the treatment without the trial,

they should have been given the treatment as they have a right to the resources available in their

country. Brody explains his argument by writing, All participants in the study, including those

in the control group, should not be denied any treatment that should otherwise be available to

him or her in light of the practical realities of health care resources available in the country in

question (Brody, 2002, p. 2). Therefore, no injustice was done to participants in the placebo

control group of the clinical trials because they should not have received zidovudine when

considering the economic reality of their country.

In light of the presented arguments, the use of placebo control groups in future studies is

morally permissible even when a current treatment is available if certain conditions are met.

Firstly, as a golden rule, research subjects must give their informed consent to participate in the

trial and understand that they may not be in the experimental group. In addition, the use of a
placebo group is justified if it is probable that the study would yield less valuable results if an

active control group or historical placebo group were used instead. A placebo group is also

justified if using an active control group would make the trial too expensive to be conducted. In

this case, no one in either the developed or developing world would receive the benefits of the

trial. Lastly, it is morally permissible to use a placebo control group if participants should not

have access to the current standard of care according to the available resources in the country in

which the trial is being conducted. It is important to note that these are not the only requirements

clinical trials must adhere to. However, these are the essential conditions that should be met if a

clinical trial is to use a placebo control group in place of an active control group.

The controversy over what is and is not morally permissible regarding the way many

historical and current clinical trials are conducted raises the question of how far we have really

come since Tuskegee was denounced as an unethical study and ethical guidelines were put in

place to prevent ethical violations in future human research studies. Marcia Angell asserts that

we have not come far at all considering the use of placebo control groups when a proven

treatment regimen is available. She writes, It is possible, with a little ingenuity, to have both

scientific and ethical rigor (Angell, 1997, p. 4). However, how realistic is it to achieve valuable

research findings when forced to adhere to the strict ethical standards she proposes? Slavish

adherence to ethical rigor would be at the expense of scientific rigor. That is not to say that

researchers cannot strike a balance between protecting their participants from ethical violations

and benefiting society through scientific studies. Contrary to the general consensus, the use of

placebo control groups is morally permissible under specific conditions. A failure to accept this

prevents scientific research from being conducted that would greatly benefit the overall health of

people throughout the world.

 References

Angell, M. (1997). The ethics of clinical research in the third world. The New England

Journal of Medicine, 337(12), 847-849. doi:10.1056/NEJM199709183371209

Brody, B. A. (2002). Ethical issues in clinical trials in developing countries. Statistics in

Medicine, 21(19), 2853-2858. doi:10.1002/sim.1289