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Placebo Comparators

Version: September 4, 2020

Guidance

A protocol that involves removing participants from the standard medication for their disease or condition, and randomizing them to receive either an investigational agent or a placebo, may raise issues of participant safety.  If some participants will receive no potentially beneficial drug for all or a significant portion of the trial, the investigator should specify in the IRB application and consent document the nature and severity of the associated risk to those participants.  Depending upon the degree of risk, the investigator should consider modification of study design to minimize the risk.

The IRB may determine that a placebo design is not acceptable if the inclusion of placebo is not adequately justified.  Use of placebo in a study design will be considered on a case-by-case basis.

During the review of a study which is designed to include placebo, board members will consider the following guidelines.

The University of Utah IRB may accept placebo comparator under any of the following situations:

  1. There are no established effective therapies for the population and for the indication under study; **
  2. Existing evidence raises substantial doubt regarding the net therapeutic benefit of available therapies;
  3. Participant(s) is/are refractory to the available therapies by virtue of their past treatment history of known medical history;
  4. The study involves adding a new investigational therapy to an established effective therapy (established effective therapy + new therapy vs. established effective therapy + placebo);
  5. Participants have determined that the response to the established effective therapies for their condition is unsatisfactory to them; or
  6. Participants have previously refused established effective therapies for their conditions.
  7. Minor health problems (This includes conditions for which both informed participants and their physicians might reasonably elect to withhold treatment (e.g., baldness, tension headache, allergic rhinitis).
  8. Placebo cross-over designs will be evaluated on a study by study process.
  9. The proposed placebo exposure is of a specified duration such that evidence supports the exposure as no more than minimal risk. Such cases will be reviewed by the IRB on a case by case basis.

** As determined by the Board

Points to Consider

New Study Application

  1. Study Information page, question 1: Please select “Placebo Controlled Trial” if the study is placebo controlled.
  2. Study Information page, question 2: Question 2 asks whether your study will involve use of any placebo. Please select “Yes.” Marking “yes” will prompt additional page(s) to complete in the ERICA system.
  3. Study Information page, question 6: When describing the procedures, please clearly describe how many participants will receive placebo, how participants that receive placebo will be selected, whether or not a “washout” period will be required (and how long the washout period will be), who will be aware of whether or not participants are on placebo or the study article (double-blind, etc.).
  4. Placebo Justification Page: Please complete this page:
    1. If you select “This trial requires a placebo-only arm although some effective treatment exists” on the Placebo Justification Page, you will also be required to complete the Placebo-Only Justification Page.
  5. Risks and Benefits Page: Please include a narrative justification for the use of placebo in the description of the risks to participants.  Please detail what measures have been taken to ensure the safety of participants that will receive placebo.

Consent Document

  1. Study Procedures: Please state the reason for the placebo or withheld treatment.
    1. Please include a short description of what a placebo
    2. Please include a description of any withheld treatment(s). Please state that because of the use of placebo, there is a chance that not all participants will receive the study article.
    3. Please include a description of any related procedures. If applicable, include any plans for rescue therapy, special monitoring, or crossover to placebo.
    4. Please describe in clear detail approximately how many participants will receive placebo, how participants that receive placebo will be selected, whether or not a “washout” period will be required (and how long the washout period will be), who will be aware of whether or not participants are on placebo or the study article (double-blind, etc.), etc.
  2. Risks: Please describe any foreseeable risks to participants with relation to the placebo or withheld treatment.
Please contact the IRB Office at (801) 581-3655 or irb@hsc.utah.edu for additional guidance.