Are Placebo-Controlled Clinical Trials Ethical or Needed When Alternative Treatment Exists?

The randomized clinical trial was a major methodologic breakthrough in medicine. For conditions having no effective treatment, the control regimen to which the new treatment is compared is usually either observation or administration of placebo. In some cases, untreated or placebo control groups are used even though effective treatment exists for the condition. Rothman (1) has challenged the ethics of such clinical trials; in the current issue, Temple and Ellenberg (2, 3) address this challenge.

There is general agreement that placebo or untreated controls are not appropriate in trials of therapy for life-threatening conditions if a treatment that prolongs or preserves life is available. The disagreement centers on trials of therapy for non–life-threatening conditions, in which a delay in administration of the effective treatment is unlikely to cause permanent harm.

Critics of placebo-controlled trials or trials that include an untreated control group cite article II.3 of the Declaration of Helsinki: “In any medical study, every patient—including those of a control group, if any—should be assured of the best proven diagnostic and therapeutic methods” (4). Rothman argues that no patient should suffer unnecessary pain, even if the condition being considered is not life-threatening: “You could torture someone for 10 minutes, and he would recover, but that doesn't mean it's a great idea  … you're supposed to be acting in the best interest of the patient  …” (1). Rothman also argues that placebo-controlled trials are unnecessary and result from “a misplaced emphasis on statistical significance testing. They never know how effective any drug is because they simply ask, ‘Is it or isn't it effective? Is it significantly better than placebo?’” (1).

Temple and Ellenberg point out that, if taken literally, the requirement of the Declaration of Helsinki that all patients receive the “best proven diagnostic and therapeutic methods” …