FDA Draft Guidance: Reduce Use of Placebo in Clinical Trials

The U.S. Food and Drug Administration (FDA) issued a draft guidance that recommends limiting the use of placebo in double-blinded cancer clinical trials.  

“Because investigators and patients in these trials do not know what treatment patients are receiving, this can decrease the likelihood of biased observations, decrease differential patient drop out, and allow for unbiased assessment of outcome measures, particularly when the assessment includes subjectivity, such as for quality of life measures,” the guidance reads. The agency noted that the use of placebo in these kinds of trials presents both practical and ethical concerns. “If possible, an active control is often preferred over placebo, and one option has been to conduct an open-label trial with a physician’s choice of one of a few standard therapies as the comparator,” according to the guideline. 

The FDA presented cases when placebo-controlled trials could be considered: 

  • Trial sponsors should provide the rationale for the trial design. This justification is particularly important in the setting of a sham surgical procedure or when invasive methods are required for the administration of the placebo. 
  • The FDA does not require patient-level maintenance of blinding at the time of disease recurrence or progression. Unless no other appropriate treatments are available, the agency recommends unblinding a patient when disease recurs or progresses. 
  • When the patient experiences an adverse event that appears to be drug-related, the FDA recommends unblinding the patient and investigator if treating the event would involve one or more drugs or an invasive procedure. The patient should not be removed from the trial after being unblinded. 
  • A detailed description in the protocol and statistical analysis plan of the proposal should be provided for both blinding (including whether the physiologic effects or adverse events associated with the investigational drug product will prevent effective blinding) and unblinding (including information regarding situations in which unblinding should occur). 
  • If blinding is continued, the informed consent document should specify the risks and potential disadvantages of this approach, and the protocol should also include justification for the potential added risk. 

Placebo-designed trials may be useful in maintenance therapy, add-on trial designs, or in trials of adjuvant therapies (where standard of care is surveillance), according to the FDA. 

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Source: FDA