The decision of whether to use an inactive placebo or an active, but potentially less effective, "standard of care," in the comparison arm of a randomized trial raises some thorny ethical issues. From a scientific standpoint, researchers often prefer to compare the effectiveness of a new treatment to no treatment at all, since a more beneficial outcome in such a trial among the active treatment group (compared to the inactive placebo group) implies that the treatment has some positive effect on the outcome of interest. However, it is conventionally considered unethical to refuse to provide the current "standard of care" treatment to individuals in the comparison arm of a study.

An even thornier ethical issue focuses on what the definition of "standard of care" should be, particularly in studies that are administered in populations without access to beneficial treatments that are widely available in developed countries. This ethical dilemma has been at the forefront of trials for preventing mother-to-child transmission of HIV in sub-Saharan Africa, where a host of randomized trials have compared the effectiveness of a treatment that is less beneficial than the current standard of care in developed countries to an inactive placebo. Those contending that such trials are ethical argue that, since there is often no available treatment for prevention of mother-to-child transmission (MTCT) in these populations, the current "standard of care" is no treatment at all. However, there are those who contend that any individuals agreeing to participate in a study should be given access to the best currently available treatment, which in the case of prevention of MTCT, is widely available in the developed world but practically unavailable in sub-Saharan Africa.

Pubmed's list of articles about this controversy .