American Conference of Pharmacometrics – “Together Moving Mountains”

Stop by and visit us in Booth #6.  

Join Simulations Plus for the following workshops:

October 29, 2022
8:00 am – 5:00 pm MDT

Title: Introductory Course on Pharmacometric Modeling with Monolix™
Main instructor: Amparo de la Peña
Secondary instructor: Monika Twarogowska

If you want to start using Monolix for your popPK/PD modeling, or you have already started and want to become a more confident user, then this course is for you. We will teach you all you need to know to develop, diagnose and interpret population models for your PK/PD datasets. After a reminder of the key concepts of the population approach, we will show you how to format your dataset, do a first exploratory data visualization, set up a model in the Monolix GUI and analyze the run results. Modeling workflows and strategies will also be discussed.

Better understanding and confidence comes from practice. You will improve it during an interactive and guided hands-on session on a typical PK/PD dataset – an opportunity to immediately apply new skills with the help from the Lixoft team.

Temporary licenses for the MonolixSuite will be provided.

October 30, 2022
8:00 am – 5:00 pm MDT

Title: Advanced course on Pharmacometrics modeling with Monolix™
Main Instructor: Pauline Traynard
Secondary instructor: Monika Twarogowska

This training is designed for modelers with already some experience of Monolix, who wish to i) better understand the algorithms and their options, ii) learn how to implement complex models, iii) improve their strategy for model building.

The course will alternate lectures and interactive hands-on sessions with Monolix.

I – Algorithms and good practices for parameter estimation

• Estimating the population parameters: theory and practice
  • SAEM and its settings
  • Assessing the convergence
  • Handling parameters without variability
  • Bayesian estimation of population parameters
• Settings of MCMC: transition kernels, automatic stopping rule
• Estimating the Fisher Information Matrix with linearization or stochastic approximation
• Estimating the likelihood with linearization or importance sampling Monte Carlo

II – Methods for statistical model building

• Diagnostics for the statistical model
  • Interpretation of diagnostic plots
  • Performing unbiased statistical tests
  • Defining and using the shrinkage correctly
• Strategies for automatic model building
  • Covariate search using COSSAC
  • Model building using SAMBA

III – Implementing complex PKPD models

• Modeling non-continuous data
• Sequential and simultaneous approaches for joint models
• Complex statistical models
  • Non-standard inter-individual variability
  • Inter-occasion variability
  • Complex covariate-parameter relationships

To register for these workshops use the ACoP13 registration form. 

If you have any questions or difficulty registering for the workshop(s), please send an email directly to info@go-isop.org.

PRESENTATIONS: 

Title: Representation of Fibrosis Stage within Mechanistic Model of Non-Alcoholic Fatty Liver Disease (NAFLD)/ Non-Alcoholic Steatohepatitis (NASH) Aligns with Histologic Assessments
Presented by: Principal Scientist Christina Battista
Date: Monday, October 31st
Time: 7:00-9:00 am, 1:00-2:30pm, 4:00-5:30pm MDT
Short description: NAFLD encompasses a histological spectrum of liver pathophysiology ranging from steatosis to NASH and may result in cirrhosis and ultimately liver failure. A reduction in fibrosis stage, which has been cited as the strongest predictor for disease-specific mortality, is a standard primary outcome when investigating efficacy of potential treatments for NASH patients. Therefore, capturing changes in fibrosis stage is critical to enable accurate predictions of efficacy for treatments within NAFLDsym®, a quantitative systems pharmacology (QSP) model that describes NAFLD pathophysiology.
Poster ID# M-059
Abstract ID # QSP459

Title: Proof-of-concept that Variable Onset and Severity of T cell-mediated Drug-Induced Liver Injury is Reproduced in a Simulated Human Population
Presented by: Scientist II Lara Clemens
Date: Monday, October 31st
Time: 7:00-9:00 am, 1:00-2:30 pm, 4:00-5:30 pm MDT
Short description: Idiosyncratic drug-induced liver injury (iDILI) is a rare, but often serious, adverse reaction that can compromise drug development. For some iDILI compounds, the adaptive immune system is implicated in the observed liver injury. Previous work extended an existing quantitative systems toxicology (QST) model, DILIsym®, to include human CD8+ T cell responses to hepatocyte-expressed amodiaquine (AQ) related neo-antigen. Here, a simulated population (SimPops™) of patients was developed with variability in characteristics related to T cell responsiveness, including susceptibility to AQ toxicity mechanisms, naïve CD8+ T cell numbers, and T cell differentiation rates. Using this SimPops, this work aimed to examine liver injury profiles and evaluate the key characteristics leading to specific responses.
Poster ID# M-043
Abstract ID # QSP476

Title: Mathematical Modeling of Renal Sodium, Potassium, and Glucose Dynamics in Diabetic and Non-diabetic Simulated Populations
Presented by: Bristol Myers Squibb (Simulations Plus coauthor: Principal Scientist Christina Battista)
Date: Monday, October 31st
Time: 7:00-9:00 am, 1:00-2:30 pm, 4:00-5:30 pm  MDT
Location: Not yet available
Short description: Type 2 diabetic (T2D) patients often exhibit reduced systolic and diastolic functions, which can place them at an increased risk of heart failure, but diuretic therapies can mitigate the risk of heart failure in these patients. To enable future efficacy predictions of diuretics, a quantitative systems pharmacology (QSP) model was developed that includes dynamic transport of solutes across different nephron segments, enabling the ability to accurately capture renal sodium, potassium, and glucose reabsorption dynamics and urinary excretion in response to novel treatments.
Poster #M-066
Abstract ID # QSP452

Title: Development of a Physiologically Based Pharmacokinetic (PBPK) Model for Pexidartinib to Evaluate the Impact of Meal Contents and Intake Timing on Drug Exposure
Poster presented by: Shintaro Nakayama, Daiichi (Simulations Plus coauthors: Jim Mullin, Sandra Suarez-Sharp, Viera Lukacova)
Date: Tuesday, November 1st
Time: Time: 7:00-9:00 am, 1:00-2:30 pm, 4:00-5:30 pm MDT
Poster ID# T-019
Abstract ID# PBPK426

Title: A Physiologically Based Pharmacokinetic Model of Long-Acting Lenacapavir
Poster presented by: Abdul Naveed Shaik, Gilead (Simulations Plus coauthor: Viera Lukacova)
Date: Tuesday, November 1st
Time: Time: 7:00-9:00 am, 1:00-2:30 pm, 4:00-5:30 pm MDT
Poster ID# T-066
Abstract ID# PBPK374

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Join us for our Lunch & Learn: “Ask the Experts”  
Moderator: Amparo de la Peña, Vice President, Pharmacometric Services, Cognigen Division
Date: Monday, October 31st, 2022  
Time: 1:00 – 2:00 pm   MDT
Location: Gaylord Rockies Event & Convention Center, Spruce Room 3 (Convention Center Level 1)  

Come meet with our teams from Cognigen, Lixoft,  DILIsym and Simulations Plus.

Seating is limited to the first 40 people. Arrive early to secure your complimentary lunch & seat.