Model‐Informed Approach to Assess the Treatment Effect Conditional to the Level of Placebo Response

One of the most important reasons for failure of placebo‐controlled randomized controlled clinical trials ( RCT s) is the lack of appropriate methodologies for detecting treatment effect ( TE ; difference between placebo and active treatment response) in the presence of excessively low/high levels of placebo response. Although, the higher the level of placebo response in a trial, the lower the apparent detectable TE . TE is usually estimated in a conventional analysis of an RCT as an “apparent” TE value conditional to the level of placebo response in that RCT . A model‐informed methodology is proposed to establish a relationship between level of placebo response and TE . This relationship is used to estimate the “typical” TE associated with a “typical” level of placebo response, irrespective of the level of placebo response observed. The approach can be valuable for providing a reliable estimate of TE , for conducting risk/benefit analysis, and for determining dosage recommendations.