Investigators conducting clinical trials in developing countries must decide what the comparator should be. As a general rule, research subjects in the control group of a trial of a diagnostic, therapeutic, or preventive intervention should receive an established effective intervention. An exception to the general rule is applicable in some studies designed to develop a therapeutic, preventive, or diagnostic intervention for use in a country or community in which an established effective intervention is not available and is unlikely in the foreseeable future to become available, usually for economic or logistic reasons. The purpose of such a study is to make available to the population of the country or community an effective alternative to an established effective intervention that is locally unavailable. Accordingly, the proposed investigational intervention must be responsive to the health needs of the population from which the research subjects are recruited, and there must be assurance that, if it proves to be safe and effective, it will be made reasonably available to that population. Also, the scientific and ethical review committees must be satisfied that the established effective intervention cannot be used as a comparator because its use would not yield scientifically reliable results that would be relevant to the health needs of the study population. In these circumstances an ethical review committee can approve a clinical trial in which the comparator is other than an established effective intervention, such as a placebo, no treatment or a local remedy.
However, some people strongly object to the exceptional use of a comparator other than an established effective intervention because it could result in the exploitation of poor and disadvantaged populations. The objection rests on three arguments:
- Placebo control could expose research subjects to a risk of serious or irreversible harm, when the use of an established effective intervention as comparator could avoid the risk.
- Not all scientific experts agree about conditions under which an established effective intervention used as comparator would not yield scientifically reliable results.
- An economic reason for the unavailability of an established effective intervention cannot justify a placebo-controlled study in a country of limited resources, when it would be unethical to conduct a study with the same design in a population with general access to the established effective intervention.
Additional information on this topic and a discussion of the arguments raised above can be found in the CIOMS International Ethical Guidelines for Biomedical Research Involving Human Subjects.