Placebo-controlled trials and active-control trials in the evaluation of new treatments. Part 2: practical issues and specific cases

Ann Intern Med. 2000 Sep 19;133(6):464-70. doi: 10.7326/0003-4819-133-6-200009190-00015.


Placebo controls are commonly used in clinical trials of investigational treatments because they have important advantages. In recent years, some have criticized the use of placebo-controlled trials when effective alternative therapy exists, regardless of the expected effect of the therapy. In part 1 of this paper, ethical arguments are addressed and the interpretive problems inherent in the use of active-control equivalence trials to establish efficacy of a new treatment are clarified. However, uncertainties may complicate decisions about appropriate use of placebo controls in some situations. Part 2 discusses more fully the ethical considerations for using placebo controls in particular medical settings. The value and relevance of placebo-controlled trials of new agents in situations in which proven effective therapy is available are also explored.

MeSH terms

  • Controlled Clinical Trials as Topic / methods*
  • Controlled Clinical Trials as Topic / standards*
  • Decision Making
  • Ethics, Medical*
  • Ethics, Research
  • Humans
  • Placebos*
  • Risk Assessment
  • Treatment Outcome


  • Placebos