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Opinion 2.075 - The Use of Placebo Controls in Clinical Trials

Placebo controls are an important part of medicine’s commitment to ensuring that the safety and efficacy of new drugs are sufficiently established. Used appropriately, placebo controls can safely provide valuable data and should continue to be considered in the design of clinical trials. The existence of an accepted therapy does not necessarily preclude the use of such controls; however, physician-investigators should adhere to the following guidelines to ensure that the interests of patients who participate in clinical trials are protected.

(1) Investigators must be extremely thorough in obtaining informed consent from patients. To the extent that research is dependent upon the willingness of patients to accept a level of risk, their understanding of the potential harms involved must be a top priority of any clinical investigation. The possibility presented in some studies that patients often do not fully understand the research protocol and therefore truly cannot give informed consent demonstrates a need to heighten the efforts of researchers to impress upon their subjects the nature of clinical research and the risks involved. Patients are capable of making decisions when presented with sufficient information, and it is the responsibility of the institutional review board (IRB) and the individual investigators involved to ensure that each subject has been adequately informed and has given voluntary consent. Each patient must also be made aware that they can terminate their participation in a study at any time.

(2) Informed consent cannot be invoked to justify an inappropriate trial design. IRBs as well as investigators have an obligation to evaluate each study protocol to determine whether a placebo control is necessary and whether an alternative study design with another type of control would be sufficient for the purposes of research. Protocols that involve conditions causing death or irreversible damage cannot ethically employ a placebo control if alternative treatment would prevent or slow the illness progression. When studying illnesses characterized by severe or painful symptoms, investigators should thoroughly explore alternatives to the use of placebo controls. In general, the more severe the consequences and symptoms of the illness under study, the more difficult it will be to justify the use of a placebo control when alternative therapy exists. Consequently, there will almost certainly be conditions for which placebo controls cannot be justified. Similarly, the use of a placebo control will more easily be justified as the severity and number of negative side effects of standard therapy increase.

(3) Researchers and IRBs should continue to minimize the amount of time patients are given placebo. The rationale provided by investigators for the length of study will give IRBs the opportunity to ensure that patients are given placebo therapy for as short a time as possible to provide verifiable results. Additionally, the interim data analysis and monitoring currently in practice will allow researchers to terminate the study because of either positive or negative results, thus protecting patients from remaining on placebo unnecessarily. (I, V)

Issued June 1997 based on the report "Ethical Use of Placebo Controls in Clinical Trials," adopted June 1996.