Placebo-Controlled Studies
Placebo-Controlled Studies
Placebo-Controlled Studies
Placebo-Controlled Studies
Background
Protocol and Consent Requirements for Use of Placebo
Protocol and Consent Form Requirements for Placebo Washout Periods
Algorithm of IRB Evaluation of Studies Involving Placebo
Background
The use of a placebo in clinical research continues to be a topic of debate in the medical community. Some
argue that use of placebos is often unethical because alternative study designs would produce similar results
with less risk to individual research participants. Others argue that the use of placebos is essential to the
protect society from the harm that could result from the widespread use of ineffective medical treatments.
Per the OHRP guidebook, "Placebos may be used in clinical trials where there is no known or available (i.e., FDA-
approved) alternative therapy that can be tolerated by subjects." The use of placebos in controlled clinical trials
must be justified by a positive risk-benefit analysis, and subjects must be fully informed of the risks involved in
assignment to the placebo group. Continued assignment of subjects to placebo is unethical once there is good
evidence to support the efficacy of the trial therapy. Some drug trials involve a period during which all
participants receive only a placebo prior to the initiation of the study. This period is called a "placebo washout."
The purposes of a washout period include:
terminating the effects of any drug the subject may have been taking before entering the clinical trial, so that the effects of
the trial drug - and only the trial drug - may be observed;
learning whether subjects cooperate with instructions to take drugs; and
learning which subjects are "placebo responders," in that they experience a high degree of placebo effect.
In some protocols, the investigators plan to exclude those subjects they find either poorly compliant or highly
responsive to the placebo. The risks entailed in withdrawing subjects from therapy during a placebo washout
period will be carefully evaluated by the IRB; great care must be taken to exclude subjects who are vulnerable to
harm or injury if they are withdrawn from effective therapy. In studies involving a placebo washout, subjects
must be told that at some point during the study all subjects will receive placebo treatment (OHRP Guidebook).
Resources:
This Algorithm will help researchers and IRBs evaluate the ethics of using a placebo-control arm in a clinical research trial.