A placebo controlled study is where subjects are randomly assigned to a placebo along with the intervention studied. In case there is no established/available (standard) treatment for a given condition; a placebo control is often the design of choice. However, questions are raised if a treatment is available that is more effective than the placebo. In such situations it is considered unethical to use a placebo without strong justifications, particularly if the illness is life-threatening. The rationale for the use of placebo for effective / standard therapy should be inclusive of the fact that it not expected to cause irreversible health problems or worsen the prevailing condition of patients. In any case, the use of placebo should be jotted with estimated risk for not receiving standard care.
The debate on the use of placebo flared after the announcement of fifth revision of Declaration of Helsinki in the year 2000. The controversy was centered with several issues such as the use of placebo may involve the methodological superiority of placebo-controlled trials in discerning treatment effects. Secondly, it was unclear if the results were mixed with placebo effects or they were confined to treatment-specific effects (excluding placebo effects). Thirdly, risk parameters for placebo groups were questioned. Since then it is much debated and the opinions of researchers are divided on the use of placebo control groups in clinical trials when effective treatment exists. (Woo J 2003)
Ad-mist this controversy, randomized placebo controlled clinical trials are still considered to be the most scientifically valid studies (the gold standard) by the regulatory agencies and the scientific community. It is not just the placebo controlled studies that are scientifically debated but also clinical trial designs such as Active Control and Historical Control (which are other different kinds of controls) that are equally & ethically questioned.
The use of placebos in controlled clinical trials should be allowed only if it is justified by a by a risk-benefit analysis with subjects being fully informed of the risks involved in assignment to the placebo group.
The following methods are used to minimize risks concerned with the use of placebos:
- No subject with high risk should be enrolled in studies which are placebo controlled.
- Sample size of placebo group should be less compared to active comparator.
- Protocol with healthy monitoring to restrict the subjects for undue risks.
- Clear guidelines for patient’s withdrawal in case of no response or prolonged placebo treatment.
- Trial Designs such with add-ons should be used to reduce the risks associated with placebo in form of maintenance treatment.
- Continuous monitoring of trials by a Data Safety Monitoring Board or performing interim analysis to evaluate safety issues.
To minimize risk, in placebo controlled studies, the informed consent form must include information that:
- Subjects have a chance of getting randomized to a placebo arm.
- A clear and lay definition of the term “placebo”.
- The rationale for using a placebo in the study.
- Potential risk as well as benefits should be included.
1) Woo J, 2003, ‘Ethical issues related to the use of placebo in clinical trials’, Hong Kong Med Journal; vol.9, pp 192-8.