Send to

Choose Destination
Clin Pharmacol Ther. 2019 Dec;106(6):1253-1260. doi: 10.1002/cpt.1584. Epub 2019 Aug 30.

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

Author information

Pharmacometrica, La Fouillade, France.
Bar Ilan University, Ramat Gan, Israel.
GlaxoSmithKline Research and Development, Collegeville, Pennsylvania, USA.
Massachusetts General Hospital, Boston, Massachusetts, USA.


One of the most important reasons for failure of placebo-controlled randomized controlled clinical trials (RCTs) 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.


Supplemental Content

Full text links

Icon for Wiley
Loading ...
Support Center