This is a clearly written proposal to investigate sources of pharmacokinetic variability for risperidone and its active metabolite, 9-hydroxy (OH)-risperidone, and examine associations with clinical outcomes. However, two aspects of the proposal may be an issue. First, I am unsure whether pharmacokinetic data were available for patients in these two trials, which could be used to estimate concentration-time profiles. Second, the authors are requesting to download certain aspects of the pharmacokinetic data, including dose, frequency of administered dose, and plasma concentrations of risperidone and 9-OH-risperidone, for non-linear mixed effects based modelling using Monolix software. Special approval would need to be secured to allow for downloading of data. Further clarification is needed.
Not ApproveSee above