Gilbert Koch
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View article: Redefining Parameter Estimation and Covariate Selection via Variational Autoencoders: One Run Is All You Need
Redefining Parameter Estimation and Covariate Selection via Variational Autoencoders: One Run Is All You Need Open
Generative Artificial Intelligence (AI) frameworks, such as Variational Autoencoders (VAEs), have proven powerful in learning structured representations from complex, high‐dimensional data. In pharmacometrics (PMX), nonlinear mixed effects…
View article: The Basel Modeling and Simulation Seminar: 20 Editions of Fostering Local Exchange in Pharmacometrics
The Basel Modeling and Simulation Seminar: 20 Editions of Fostering Local Exchange in Pharmacometrics Open
This year marks the 20th edition of the Basel Modeling and Simulation (M&S) Seminar, an initiative rooted in a commitment to promoting the exchange of the latest advancements in pharmacometrics and related disciplines in the region of Base…
View article: Influence of Disease Type and Activity on Adalimumab Exposure in Children with Inflammatory Rheumatic Diseases
Influence of Disease Type and Activity on Adalimumab Exposure in Children with Inflammatory Rheumatic Diseases Open
Understanding adalimumab pharmacokinetics (PK) in pediatric inflammatory rheumatic diseases (PIRD) could facilitate individualized treatment strategies. This pharmacometric (PMX) analysis, utilizing prospectively collected data, aimed to d…
View article: Assessing accuracy of BiliPredics algorithm in predicting individual bilirubin progression in neonates—results from a prospective multi-center study
Assessing accuracy of BiliPredics algorithm in predicting individual bilirubin progression in neonates—results from a prospective multi-center study Open
Background Neonatal jaundice affects more than half of neonates. As bilirubin values usually peak few days after hospital discharge, jaundice remains a leading cause of rehospitalization. The recently developed BiliPredics algorithm, integ…
View article: Low‐dimensional neural ordinary differential equations accounting for inter‐individual variability implemented in Monolix and <scp>NONMEM</scp>
Low‐dimensional neural ordinary differential equations accounting for inter‐individual variability implemented in Monolix and <span>NONMEM</span> Open
Neural ordinary differential equations (NODEs) are an emerging machine learning (ML) method to model pharmacometric (PMX) data. Combining mechanism‐based components to describe “known parts” and neural networks to learn “unknown parts” is …
View article: Computing optimal drug dosing regarding efficacy and safety: the enhanced OptiDose method in NONMEM
Computing optimal drug dosing regarding efficacy and safety: the enhanced OptiDose method in NONMEM Open
Recently, an optimal dosing algorithm (OptiDose) was developed to compute the optimal drug doses for any pharmacometrics model for a given dosing scenario. In the present work, we enhance the OptiDose concept to compute optimal drug dosing…
View article: Understanding time to peak effect of propofol as sole agent on bispectral index in children aged 2–12 years
Understanding time to peak effect of propofol as sole agent on bispectral index in children aged 2–12 years Open
Background The pharmacodynamics of propofol in children have previously been described with the proprietary bispectral index (BIS) as an effect‐site marker, and it has been suggested that the rate of onset of propofol might be age dependen…
View article: Applying Neural ODEs to Derive a Mechanism‐Based Model for Characterizing Maturation‐Related Serum Creatinine Dynamics in Preterm Newborns
Applying Neural ODEs to Derive a Mechanism‐Based Model for Characterizing Maturation‐Related Serum Creatinine Dynamics in Preterm Newborns Open
Serum creatinine in neonates follows complex dynamics due to maturation processes, most pronounced in the first few weeks of life. The development of a mechanism‐based model describing complex dynamics requires high expertise in pharmacome…
View article: Computing optimal drug dosing regarding efficacy and safety - the enhanced OptiDose method in NONMEM
Computing optimal drug dosing regarding efficacy and safety - the enhanced OptiDose method in NONMEM Open
Recently, an optimal dosing algorithm (OptiDose) was developed to compute the optimal drug doses for any pharmacometrics model for a given dosing scenario. In the present work, we enhance the OptiDose concept to compute optimal drug dosing…
View article: FRI478 Pharmacometrics-based Computer Model Utilizing Heart Rate To Monitor Thyroid Function In Children With Graves' Disease
FRI478 Pharmacometrics-based Computer Model Utilizing Heart Rate To Monitor Thyroid Function In Children With Graves' Disease Open
Disclosure: B. Steffens: None. G. Koch: None. F. Claude: None. F. Bachmann: None. J. Schropp: None. M. Janner: None. D. l'Allemand: None. D. Konrad: None. M. Pfister: None. G. Szinnai: None. Graves’ disease (GD) with onset in childhood or …
View article: PMX NN Repair: Datasets, Networks and Virtual Machine
PMX NN Repair: Datasets, Networks and Virtual Machine Open
Supplementary Material for the Paper "Can we trust neural networks in pharmacometrics? Yes, wec an, but we need guarantees!" by David Boetius, Dominic Stefan Bräm, Marc Pfister, Stefan Leue, and Gilbert Koch.
View article: PMX NN Repair: Datasets, Networks and Virtual Machine
PMX NN Repair: Datasets, Networks and Virtual Machine Open
Supplementary Material for the Paper "Can we trust neural networks in pharmacometrics? Yes, wec an, but we need guarantees!" by David Boetius, Dominic Stefan Bräm, Marc Pfister, Stefan Leue, and Gilbert Koch.
View article: Clinically practical pharmacometrics computer model to evaluate and personalize pharmacotherapy in pediatric rare diseases: application to Graves' disease
Clinically practical pharmacometrics computer model to evaluate and personalize pharmacotherapy in pediatric rare diseases: application to Graves' disease Open
Objectives Graves' disease (GD) with onset in childhood or adolescence is a rare disease (ORPHA:525731). Current pharmacotherapeutic approaches use antithyroid drugs, such as carbimazole, as monotherapy or in combination with thyroxine hor…
View article: Neural ODEs in Pharmacokinetics: Concepts and Applications
Neural ODEs in Pharmacokinetics: Concepts and Applications Open
Machine Learning (ML) is a fast-evolving field, integrated in many of today’s scientific disciplines. With the recent development of Neural Ordinary Differential Equations (NODEs), ML provides a new tool to model dynamical systems in the f…
View article: Evaluation of machine learning methods for covariate data imputation in pharmacometrics
Evaluation of machine learning methods for covariate data imputation in pharmacometrics Open
Missing data create challenges in clinical research because they lead to loss of statistical power and potentially to biased results. Missing covariate data must be handled with suitable approaches to prepare datasets for pharmacometric an…
View article: Leveraging Predictive Pharmacometrics-Based Algorithms to Enhance Perinatal Care—Application to Neonatal Jaundice
Leveraging Predictive Pharmacometrics-Based Algorithms to Enhance Perinatal Care—Application to Neonatal Jaundice Open
The field of medicine is undergoing a fundamental change, transforming towards a modern data-driven patient-oriented approach. This paradigm shift also affects perinatal medicine as predictive algorithms and artificial intelligence are app…
View article: Computing optimal drug dosing with OptiDose - Implementation in NONMEM
Computing optimal drug dosing with OptiDose - Implementation in NONMEM Open
Finding a drug dosing recommendation with a PKPD model for an individual or a target population can be a laborious and complex task. Recently, an optimal dosing algorithm (OptiDose) was developed to compute the optimal doses for any pharma…
View article: Modeling of levothyroxine in newborns and infants with congenital hypothyroidism: challenges and opportunities of a rare disease multi-center study
Modeling of levothyroxine in newborns and infants with congenital hypothyroidism: challenges and opportunities of a rare disease multi-center study Open
Modeling of retrospectively collected multi-center data of a rare disease in pediatrics is challenging because laboratory data can stem from several decades measured with different assays. Here we present a retrospective pharmacometrics (P…
View article: OptiDose: Computing the Individualized Optimal Drug Dosing Regimen Using Optimal Control
OptiDose: Computing the Individualized Optimal Drug Dosing Regimen Using Optimal Control Open
Providing the optimal dosing strategy of a drug for an individual patient is an important task in pharmaceutical sciences and daily clinical application. We developed and validated an optimal dosing algorithm (OptiDose) that computes the o…
View article: A Sensitivity Analysis of the Optimal Drug Dosing Algorithm OptiDose
A Sensitivity Analysis of the Optimal Drug Dosing Algorithm OptiDose Open
OptiDose is a drug dosing algorithm that computes the optimal doses for a given patient and dosing schedule based on control theory. Here, a sensitivity analysis for OptiDose using derivative based and regression methods is performed. Two …
View article: Copeptin Kinetics and Its Relationship to Osmolality During Rehydration for Diabetic Ketoacidosis in Children
Copeptin Kinetics and Its Relationship to Osmolality During Rehydration for Diabetic Ketoacidosis in Children Open
Context Copeptin is a surrogate marker for arginine vasopressin (AVP) release in response to hyperosmolal stimuli such as diabetic ketoacidosis (DKA). Objective The objective of this work is to characterize kinetics of copeptin and osmolal…
View article: Caffeine preserves quiet sleep in preterm neonates
Caffeine preserves quiet sleep in preterm neonates Open
Caffeine is widely used in preterm neonates suffering from apnea of prematurity (AOP), and it has become one of the most frequently prescribed medications in neonatal intensive care units. Goal of this study is to investigate how caffeine …
View article: MON-081 Mathematical Modeling of Residual Endogenous FT4 Synthesis and Exogenous L-Thyroxine Administration over the First 2 Years of Life in Infants with Congenital Hypothyroidism
MON-081 Mathematical Modeling of Residual Endogenous FT4 Synthesis and Exogenous L-Thyroxine Administration over the First 2 Years of Life in Infants with Congenital Hypothyroidism Open
L-Thyroxine (L-T4) is the treatment of choice of congenital hypothyroidism (CH). Longitudinal measurements of free T4 (FT4) serum concentrations were collected over the first two years of life with oral L-T4 treatment in infants with CH. P…
View article: MON-102 Serum Concentrations of FT4 and TSH in the First Six Months of L-Thyroxine Treatment in Infants with Congenital Hypothyroidism: Target Attainment Rates Should Be Improved
MON-102 Serum Concentrations of FT4 and TSH in the First Six Months of L-Thyroxine Treatment in Infants with Congenital Hypothyroidism: Target Attainment Rates Should Be Improved Open
Levo-Thyroxine (L-T4) is the medication of choice for treating congenital hypothyroidism (CH). Adequate L-T4 treatment is essential for early neurodevelopment in affected patients. Both under- and overtreatment with L-T4 were associated wi…
View article: Pharmacometrics and Machine Learning Partner to Advance Clinical Data Analysis
Pharmacometrics and Machine Learning Partner to Advance Clinical Data Analysis Open
Clinical pharmacology is a multidisciplinary data sciences field that utilizes mathematical and statistical methods to generate maximal knowledge from data. Pharmacometrics (PMX) is a well‐recognized tool to characterize disease progressio…