This repository contains the code and data used in the analysis for the publication "Optimising covariate allocation at design stage using Fisher Information Matrix for Non-Linear Mixed Effects Models in pharmacometrics" Main Script **`run_all.R`**: Master script to run the entire analysis pipeline. Folder Structure - **`/my_pmxcopula`** Source code for the R package `pmxcopula` [@pmxcopula], used for copula fit diagnostic plots. This version includes minor edits. Original source: vanhasseltlab/pmxcopula. - **`/PFIM_6_1_beta_cov`** Contains `PFIM6.1_beta_cov` [@fayette_2024_13692989], an adapted version of the `PFIM6.1` R package [@pfim6], available at Zenodo. - **`/Concentrations_covariates`** Includes figures showing the evolution of concentration \( f(t) \) with respect to fixed and covariate effects. - **`/HepaticFunction`** Results and scripts for the Hepatic Function (HF) example. - **`/RenalFunction`** Results and scripts for the Renal Function (RF) example. - **`/NHANES`** Contains NHANES datasets (2009–2020) [@NHANES20092020] and the transformed covariate dataset used in the analysis. - **`/tikzDictionary`** TikZ dictionary for LaTeX-based plotting. R Scripts Data Preparation & Plotting - `00_NHANES_create_database_RF_HF.R`: Creates the transformed covariate database from NHANES data.- `01_Concentrations_covariates.R`: Plots concentration evolution figures. Utility Functions - `funct.R`: Loads required libraries and general functions.- `funct_diag_copula.R`: Diagnostic functions for copula fits.- `funct_Plot_Latex.R`: Plotting functions using `tikzDevice` for LaTeX output.- `funct_ProjectedGradient.R`: Functions for the Projected Gradient Descent (PGD) algorithm.- `funct_resOptim.R`: Functions to extract optimisation results. Hepatic Function (HF) Example - `HF_02_fit_copula_pooled_vine.R`: Fits copulas and generates diagnostics.- `HF_03_PFIM_GQ.R`: Computes FIM using Gauss-Legendre Quadrature.- `HF_03_PFIM_MC.R`: Computes FIM using Monte Carlo methods.- `HF_04_Cov_Opti.R`: Optimises covariate distribution. Renal Function (RF) Example - `RF_02_fit_copula_pooled_vine.R`: Fits copulas and generates diagnostics.- `RF_03_PFIM_GQ_varying_beta.R`: Computes FIM using Gauss-Legendre Quadrature with varying beta.- `RF_03_PFIM_MC.R`: Computes FIM using Monte Carlo methods.- `RF_04_Cov_Opti_varying_beta.R`: Optimises covariate distribution.