Dampening Placebo Effect with Enriched Run-In Design in Randomized Clinical Trials

• Activity Number: 441 - Bayesian (and Other) Clinical Trials Designs
• Type: Contributed
• Date/Time: Thursday, August 12, 2021 : 4:00 PM to 5:50 PM
• Sponsor: Biopharmaceutical Section
• Author(s): Ping Xu* and qing li and Richard Entsuah
• Companies: Merck & Co. and Merck & co., Inc. and Merck & Co.
• Keywords: Placebo Effect; Run-in period; Statistical Power

Abstract

In randomized clinical trials for the treatment of a chronic disease that is not life-threatening where there is no existing proven treatment available, testing against placebo is deemed to be the standard test for efficacy. The placebo effect is an impediment—a phenomena that interferes with statistical evaluation of a potentially genuine drug or treatment effect. Preceded by a placebo run-in period, the placebo effect can be mitigated or minimized prior to randomization.By factoring out the placebo effect in the relative change of a clinical outcome during the post-randomization period,the treatment difference becomes more observable.Under a range of placebo effects,from mild to severe, simulation results demonstrated that a trial design enriched with a placebo run-in period could dampen the placebo effect in testing treatment and lead to more statistical power as much as 20% or more.We conclude that RCTs of drugs for chronic disease with placebo run-in periods have potential merits in boosting statistical power for testing true treatment difference with an increased probability of detecting any significant improvement in clinical outcomes attributed to the new drug or treatment.