Value assessment of oncology drugs using a weighted criterion-based approach.

Background: Globally, the rising cost of anticancer therapy has motivated efforts to quantify the overall value of new cancer treatments. Multicriteria decision analysis offers a novel approach to incorporate multiple criteria and perspectives into value assessment.

Methods: The authors recruited a diverse, multistakeholder group who identified and weighted key criteria to establish the drug assessment framework (DAF).

Age and sex impact clozapine plasma concentrations in inpatients and outpatients with schizophrenia.

Background: Although clozapine is primarily used in a younger to mid-life population of patients with psychosis, there are limited data on the clinical pharmacology of clozapine later in life. The objective of this study was to assess the magnitude and variability of plasma concentrations of clozapine and norclozapine across the lifespan in a real-world clinical setting.

Design: A population pharmacokinetic study using nonlinear mixed effect modeling (NONMEM).

Clozapine and global cognition in schizophrenia.

Objective: Clozapine (CLZ) has been shown to have a beneficial effect on cognition in schizophrenia in some studies and a detrimental effect in others. The relative effect and exposure to CLZ and its major metabolite-N-desmethylclozapine (NDMC)-could explain these discrepancies.

Methods: Using a validated measure of global cognition, we performed 2 binary logistic regression models to assess the relationship among cognition, age, sex, CLZ dose, CLZ and NDMC plasma levels, and their ratio (CLZ/NDMC) in individuals with schizophrenia spectrum disorders.

Clozapine exposure and the impact of smoking and gender: a population pharmacokinetic study.

The primary objective of this study was to evaluate the magnitude and variability of concentration exposure to clozapine and norclozapine in a real-world clinical setting, with a focus on smoking status, using population pharmacokinetic methodologies. A retrospective review of plasma clozapine and norclozapine concentrations taken from inpatients at the Centre for Addiction and Mental Health, Toronto, from 2001 to 2007 was conducted. A nonlinear mixed-effects model was developed using NONMEM, including age, gender, weight, smoking status, and dosage formulation as covariates.