Mechanistic models are utilized in individual analysis using single-source data, but imperfections arise due to data collection errors, preventing perfect prediction of observed data. The mathematical equation involves known values (Xi), observed concentrations (Ci), measurement errors (εi), model parameters (ϕj), and the related function (ƒi) for i number of values. Different least-squares metrics quantify differences between predicted and observed values. The ordinary least squares (OLS) method favors better predictions for larger observations. In contrast, weighted least squares (WLS) and maximum likelihood/expected least squares (ML/ELS) methods improve OLS by incorporating a weighting factor.
Population analysis models predict concentration data for multiple individuals, accounting for interindividual variability and providing individual and population predictions. The same structural model fits all individuals' data for a specific drug under study. Different types of population compartmental analysis include naïve-average data, naïve pooled data, and the two-stage approach, which includes standard, global, and iterative types. In the two-stage approach, population parameter estimates are obtained through iterative processes, such as standard two-stage (STS) and global two-stage (GTS).
From Chapter 7:
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