Comment on “An Integrated Pharmacokinetic–Pharmacodynamic–Pharmacoeconomic Modeling Method to Evaluate Treatments for Adults with Schizophrenia”

Response to Comment on “An Integrated Pharmacokinetic-Pharmacodynamic-Pharmacoeconomic Modeling Method to Evaluate Treatments for Adults with Schizophrenia”

“…As mentioned in the introduction section of our article, the purpose of this article was to present an application of a novel pharmacokinetic–pharmacodynamics–pharmacoeconomic (PK–PD–PE) framework that would enable pharmacoeconomic comparisons of the aripiprazole lauroxil (AL) and aripiprazole monohydrate (AM) long-acting injectable formulations based on publicly available, where possible peer-reviewed sources given that no comparative clinical evidence currently exists. It is our understanding that Dr. Rege and colleagues [ 1 ] question the validity of the PD inputs of our PK–PD–PE model as well as the validity of the pharmacoeconomic conclusions of our study. For the reasons explained below, we stand behind the validity of our model and our conclusions in the article.…”

“…We appreciate the opportunity to respond to the comments submitted to you by Dr. Bhaskar Rege and colleagues [ 1 ] regarding our October 2021 article entitled, “An integrated pharmacokinetic–pharmacodynamic–pharmacoeconomic modeling method to evaluate treatments for adults with schizophrenia” [ 2 ]. As mentioned in the introduction section of our article, the purpose of this article was to present an application of a novel pharmacokinetic–pharmacodynamics–pharmacoeconomic (PK–PD–PE) framework that would enable pharmacoeconomic comparisons of the aripiprazole lauroxil (AL) and aripiprazole monohydrate (AM) long-acting injectable formulations based on publicly available, where possible peer-reviewed sources given that no comparative clinical evidence currently exists.…”

“…In addition, as both AM and AL exert their action via the common active aripiprazole, it is plausible to assume the same aripiprazole exposure–response relationship for both formulations. The difference between the long-acting injectable formulations is not in the pharmacodynamics but in the pharmacokinetics of the two formulations (i.e., the different PK profiles), as mentioned by the commentators [ 1 ]. We account for those differences between the formulations in the PK part of our PK–PD–PE analysis.…”

“…Third, the commentators [ 1 ] question the use of a dichotomous hazard function for C min . As explained above, the use of this hazard function is validated against observed clinical trial data and considered robust to predict the probability of relapse.…”

Comment on “Aripiprazole Plasma Concentrations Delivered from Two 2-Month Long-Acting Injectable Formulations: An Indirect Comparison” [Letter]

“…1 However, Harlin et al also acknowledge that minimum therapeutic aripiprazole levels have been debated, 1 and we agree that the ≥95 ng/mL value is based on a flawed analysis of aripiprazole once monthly that did not include any AL data. 5 Given the distinct PK profiles associated with AL, the exposure-response analysis for aripiprazole would have potentially resulted in a different cutoff level had AL-related exposure and efficacy data been considered.…”