Protocol and Consent Requirements for Use of Placebo

Researchers that conduct clinical investigations that involve the use of placebo must complete Appendix L of the electronic IRB Application. Researchers must:

justify the use of the placebo, compare the use of placebo to standard therapy, and outline the methodology that will be used to minimize risks to subjects. If vulnerable populations are included in the study, the investigator must discuss and justify their participation and detail how subjects will be adequately protected.

The following are methods that can be used to minimize risks associated with the use of placebo:

Exclude subjects with an increased risk of harm from non-response. Include in the protocol increased monitoring for subject deterioration and the use of rescue medications. "Early escape" mechanisms and explicit withdrawal criteria may be built in so subjects will not undergo prolonged placebo treatment if they are not doing well. The size of the population placed on placebo may be smaller than the number in active treatment arms. Placebo and active treatment may be compared in an "add-on" method, keeping the subjects on identical maintenance treatments and then adding on the active treatment to one arm and placebo to the other. This design is especially applicable when the available treatment is known to decrease mortality or morbidity. Shortened treatment periods reduce the risks associated with delayed treatment. In situations in which long-term placebo treatment would not be acceptable, the use of a placebo group for a short period at the beginning of a trial could establish short-term effects. The trial would then continue without the placebo group. Unblinded data review by a Data Safety Monitoring Board with interim analysis of study results and safety issues. This is especially important for multi-center site studies.

If a placebo is used in a study, the informed consent form must include all of the following information:

Subjects must be informed that they may be given a placebo. A clear lay definition of the term "placebo." The rationale for using a placebo must be explained to the subjects. If applicable, subjects must be informed of any viable medical alternatives to being placed on placebo. The duration of time that a subject will be on a placebo, degree of discomfort, and potential effects of not receiving medication must all be explained. Any consequences of delayed active treatment must be explained to the subjects. A statement in the Risk section of the consent that the subject's condition may worsen while on placebo. A discussion in the Benefits section that subjects who receive placebo will not receive the same benefit as those who receive active treatment if that treatment is effective.