Loma Linda University’s IRB has developed the following guidelines for the use of placebos in research in psychopharmacology. The principles that are foundational to these guidelines may be helpful in considering the use of placebos in non-psychopharmacology situations.

Purpose. These guidelines have been developed to address concerns about the use of placebos in clinical trials involving vulnerable subjects who may not be able to reason clearly about their options because of impairment from psychiatric illness. They are meant to assist investigators and the IRB in the development and evaluation of protocols. Submitted protocols which do not meet these criteria will not be approved by the IRB unless the investigator is able to demonstrate clear scientific and ethical justification.

  1. Design of Research Protocols

    • The use of placebo controls may be justified when:
      • there is no standard treatment with proven efficacy;
      • standard treatment is of questionable efficacy;
      • standard treatment has unacceptable toxicity.
    • Subjects may not remain in a placebo controlled trial for more than 6 weeks (or some other time period approved by the IRB) unless they demonstrate evidence of improvement in clinical symptoms or side-effect profile.
    • Subjects may not be enrolled in a placebo-controlled drug trial unless they are concurrently being given other interventions known to have a potentially positive impact on their condition, e.g., other pharmacotherapy, hospitalization, individual or group psychotherapy.
    • A placebo “wash-out” period may be warranted in some studies, but not to exceed 7 days.

  2. Inclusion criteria:

    • those who have failed to respond to standard therapy for their condition,
    • those who have been partial responders to standard therapy for their condition, but continue to exhibit moderate or more impairment which is deemed unacceptable by the patient or an independent psychiatrist not associated with the research,
    • those who have responded to standard therapy for their condition but who have experienced side effects deemed unacceptable by themselves or an independent psychiatrist not associated with the research.

  3. Exclusion criteria:

    • those who have not received an adequate trial of standard therapy for their condition,
    • those who have received standard therapy for their condition in the past and had an acceptable clinical response without unacceptable side effects,
    • those whose condition is currently adequately controlled and stable on standard therapy without unacceptable side effects.

  4. Consent: Consent observers who are independent of the investigator and of the institution will be required by the IRB in those conditions where the potential subject’s decision-making capacity is suspect.

  5. Monitoring: Validated quantitative instruments must be used at entry and serially to assess improvement or deterioration; the frequency of assessment must be specified and must be approved by the IRB.

  6. Enrollment

    • A subject must be automatically disenrolled if serial monitoring (See 5 above) shows a pre-determined degree of overall deterioration greater than that expected for normal clinical fluctuation in a patient with that diagnosis who is on standard therapy.
    • A subject must be automatically disenrolled if serial monitoring shows a pre-determined degree of deterioration in one or more specific clinical parameters which might present a danger to the patient or to others (e.g. hostility), even if there is not sufficient deterioration in the overall monitoring score to trigger disenrollment.
    • A subject must be automatically disenrolled if serial monitoring shows no improvement in clinical symptoms or side-effect profile after 6 weeks on protocol (or some other time limit established by the IRB).
    • As with any study, subjects may discontinue at any time for any reason.