The leading ethical position on placebo-controlled clinical trials
Is that whenever proven effective treatment for a given condition, it is unethical to test a new treatment for that condition against a placebo.
Invoking the principle of clinical equipoise, opponents of placebo-controlled trials in the face of proven effective treatment argue that they (1) violate the therapeutic obligation of physicians to offer optimal medical care and (2) lack both scientific and clinical merit.
We contend that both of these arguments are mistaken. Clinical equipoise provides erroneous ethical guidance in the case of placebo-controlled trials because it ignores the ethically relevant distinction between clinical trials and treatment in the context of clinical medicine and the methodological limitations of active-controlled trials.
Placebo controls are ethically justifiable when they are supported by sound methodological considerations and their use does not expose research participants to excessive risks of harm.
The placebo-controlled clinical trial has a long history of being the standard for clinical investigations of new drugs.
By blindly and randomly allocating similar patients to a control group that receives a placebo and an experimental group, investigators can ensure that any possible placebo effect will be minimized in the final statistical analysis.
Although this approach to clinical research is scientifically sound, ethical concerns arise in some cases that outweigh the benefits of this protocol design. Even though patients may be advised of the likelihood of being placed in a placebo group and that the intent of the clinical trial is research, not medical care, they often hope for some level of treatment.
More importantly, when effective treatments exist, research participants who have progressive, the burdensome disease should be given standard treatment as the control agent.
The use of placebo controls in clinical research that involves patients who have an active disease for which there is approved treatment is ethically questionable and may represent substandard care.
The use of active or historical controls in clinical research may address these ethical questions.
Federal guidelines say that a condition of clinical equipoise should exist before a placebo-control study is started. Although this is a reasonable guideline, sponsors or investigators may be ignoring it.
Research participants with active disease are likely to believe they will possibly benefit from taking part in trials. This therapeutic misconception may not be obviated by an informed consent form.
Many documents base their guidance on protecting human participants. At times, however, federal regulations may conflict with the ethical guidelines provided by the Office for Protection from Research Risk (OPRR).