All Publications

Confounded exposure metrics

Exposure-response (E-R) modeling frequently relies on the use of exposure metrics that summarize drug concentrations over time. This research presents simulations to demonstrate that certain commonly used exposure metrics, including average concentration up to an event time, are likely to lead to causal confounding under the very conditions that motivate their use.

Expanding Statistical Influence in Pharmacometrics: What it Means, Why it Matters, and How to Make it Work

Many biostatisticians in pharma and biotech  have relatively little awareness of, let alone influence over, the heavily statistical “pharmacometric” reasoning that goes into CTD Section 2.7.2 of an FDA regulatory submission, the “Summary of Clinical Pharmacology Studies”.  This talk focuses on the value of increasing statistical influence in pharmacometrics and the path to get there.

Population Pharmacokinetic (PK) and Exposure-Response (ER) Analysis of Empagliflozin in Pediatric Patients with Type 2 Diabetes Mellitus (T2DM)

Presented at ACoP14. Empagliflozin, effective for type 2 diabetes in adults and children, underwent Study 1218.91 to assess its safety and efficacy over 26 weeks (with potential extension to 52 weeks) in children and adolescents. Using pediatric data from this study, researchers re-evaluated empagliflozin’s models in a Bayesian framework. Results showed similar drug exposure between children and adults at a 10 mg dose. At week 26, pediatric patients displayed a slightly larger but variable decrease in A1c compared to adults. This Bayesian method allowed insights into empagliflozin’s effects in children, drawing from knowledge gained in adult studies.

simpar: an R Package for Parameter Uncertainty Simulations in Pharmacometric Modeling

Presented at ACoP14. This project is dedicated to integrating parameter uncertainty into pharmacometric simulations, which plays a crucial role in making informed decisions in drug development. Initially, the metrumrg package in R was instrumental for simulating both fixed and random effect parameters. However, this package has since been deprecated. Consequently, the primary objective was to create a new R package named simpar. This new package aimed to retain the essential functionalities of metrumrg while expanding its capabilities. The overarching goal was to significantly enhance the support for incorporating parameter uncertainty into pharmacometric simulations, thereby aiding more comprehensive and accurate decision-making processes in this field.

Population Pharmacokinetic and Exposure-Response Analysis of Linagliptin in Pediatric Patients with Type 2 Diabetes Mellitus

Presented at ACoP14. This study assessed linagliptin’s effectiveness and safety in children and adolescents with type 2 diabetes over 26 weeks, potentially extending to 52 weeks. The study re-evaluated models developed for adults and adolescents to understand linagliptin’s impact on pediatric patients’ HbA1c levels. Results indicated slightly higher and more varied linagliptin exposure in children compared to adults at a 5 mg dose. Although pediatric patients had a smaller and variable HbA1c reduction versus adults at week 26, the Bayesian approach helped characterize linagliptin’s effects in children based on limited data, borrowing insights from adult studies.

Bayesian Borrowing in the DINAMO Pediatric Study using Informative Priors Derived from Model-based Extrapolation

Presented at ACoP14. The DINAMO study assessed empagliflozin and linagliptin’s effectiveness and safety in treating type 2 diabetes in children. Using prior models based on adult data, the study predicted these medications’ effects in younger populations following FDA guidelines. Employing a Bayesian analysis with robust prior specifications, the study justified its approach by considering factors like weight, kidney function, age, race, and gender when extrapolating adult outcomes to pediatric populations.

UDE Know It If UDE Saw It: Leveraging Deep Machine Learning for QSP Model Development and Evaluation

Roller Coaster Talk presented at ACoP14. A workflow was introduced that integrates QSP modeling and machine learning in the form of UDEs. The workflow utilizes machine learning to learn missing parts in our knowledge of a QSP system while quantifying the uncertainty around the learned dynamics using Bayesian analysis.

Development of a dynamic Parkinson’s Disease database with user interface tools as a basis for internal and regulatory decision making

Presented at ACoP14. The objective of this work is to integrate multiple PD clinical studies, harmonize the data, and deploy a user interface for rapid data interrogation and analysis subset generation.

Integrated Population Pharmacokinetic Analysis of Conjugated and Unconjugated Payload of Patritumab Deruxtecan in Cancer Patients

Presented at ACoP14. Patritumab deruxtecan (HER3-DXd) is a human epidermal growth factor receptor (HER3)-targeting antibody-drug conjugate with a topoisomerase I inhibitor payload (DXd). The drug-to-antibody ratio is approximately 8. HER3-DXd is currently being investigated as an anticancer agent in several phase 1-3 clinical studies in breast cancer (BC) and nonsmall cell lung cancer ( NSCLC) patients.

Deep QSP Modeling: Leveraging Machine Learning for QSP Model Development and Evaluation

Presented at ACoP14. DQSP framework successfully implemented a UDE that characterized the PK of remoxipride and its effect on PRL release from lactotrophs to plasma. The model also characterized the positive feedback effect of plasma PRL on lactotroph PRL stimulation using an ANN.

Exposure-Response Analyses of Efficacy and Safety of Patritumab Deruxtecan in Cancer Patients

Presented at ACoP14. ER analyses showed that the 5.6 mg/kg Q3W regimen offers a positive benefit-risk profile with clinically meaningful efficacy and overall manageable and tolerable safety profile. The analyses results support the selection of 5.6 mg/kg Q3W as the recommended dose for further clinical development of HER3-DXd monotherapy.

A multi-organ integrated QSP model for hematopoietic stem cell differentiation to predict the immune cell reconstitution in ex-vivo gene therapy

Presented at ACoP14. The differentiation of mammalian hematopoietic stem cells (HSCs) is complex and multiscale, providing an opportunity for mathematical modeling and simulation to aid in mechanistic understanding, and ultimately, to inform drug development efforts. Historically, HSC mathematical models were focused on the development of a subset of cells, but mathematical models encompassing the overall cellular system’s complexity are rarely available. Here, an integrated quantitative systems pharmacology (QSP) model that characterizes multi-organ HSC differentiation was developed by integrating literature models and adding novel features.

Connecting ISoP with Statisticians: An Introduction to the Biopharmaceutical Section of the American Statistical Association

Presented at ACoP14. The American Statistical Association (ASA) comprises regional chapters and specialized sections, including the Biopharmaceutical Section (BIOP), established in 1981. BIOP focuses on applying statistics to drug development, biologics, devices, and related technologies in humans and animals. Initially created to connect ISoP and ASA, SxP employs innovative statistical methods to address similar inquiries, despite using distinct terminologies and assumptions in modeling. This poster offers insight into BIOP’s history, objectives, organization, and avenues for involvement or contacting its members.

Illustrating Integration and Interpretation of the Deep Compartment Model Approach using Keras and R in a Population PK Modeling Analysis

Presented at ACoP14. Deep compartment models (DCMs) are a proposed alternative to traditional nonlinear mixed effect (NLME) pharmacometrics approaches [1]. DCM uses neural networks to represent estimated pharmacokinetic parameters which can then be used in either closed-form or ordinary differential equation (ODE)-based representations of pharmacokinetic models

Exploring the Influence of Bispecific Antibody Mechanisms on In Vitro Dose Response: Insights from an Open-Science Quantitative Systems Pharmacology Model in Julia

Presented at ACoP14. Analysis of the QSP model found that the internalization rate of the target receptors may be an important, yet often underestimated, factor for understanding bsAb efficacy in vitro. Simulations of the model indicated that high rates of receptor turnover can increase model predictions of efficacy, particularly at higher antibody concentrations.

Hierarchical Deep Compartment Modeling: A Workflow to Leverage Machine Learning for Hierarchical Pharmacometric Modeling

ACoP14 Abstract Quality Award winner. The Hierarchical Deep Compartment Modeling (HDCM) framework introduced in this abstract was developed using open-source tools in the Julia Programming Language and integrated Bayesian inference to quantify the uncertainty around the model parameters. It provides a convenient, readily accessible HDCM framework to the pharmacometrics community interested in applying deep learning to hierarchical compartmental models.

Hands-On Tutorial: Introduction to Immuno-Oncology (IO) Quantitative Systems Pharmacology (QSP) Modeling Using the Open Source Julia Programming Language

ACoP14 pre-meeting workshop. Highlights include exploring Julia as an open source alternative for QSP support of model-informed drug development, gaining insights into IO QSP modeling for antibody drug conjugate (ADCs) and bispecific mAb (bsAb) therapies to drive your own implementations of Project Optimus, and accessing open source Julia versions of two pivotal IO models and parameterizations.

Quantitative Systems Pharmacology in Model-Informed Drug Development

When tailored for specific questions, QSP models enhance our grasp of clinical observations, guiding research with informed decisions, especially when they incorporate mechanistic insights. These models facilitate the integration of theory and data to test our understanding and explore the root causes of events. By offering quantifiable insights into the interactions within physiology, disease, and pharmacology, QSP models steer further research, impacting study design and biomarker selection. The presentation will encompass case studies on monoclonal antibody (mAb) development in bone health (osteoporosis), infectious disease (SARS-CoV-2), and oncology (relapsed/refractory diffuse large B-cell lymphoma).

A Clinical Quantitative Systems Pharmacology Framework Describing Loncastuximab Tesirine Distribution and to Explore Patient Outcomes From the LOTIS-2 Clinical Trial in Patients With B-cell Lymphomas

A novel QSP framework integrating PBPK modeling with tumor dynamics was developed using literature and in-house data. By employing a virtual population reflecting patients treated with Lonca, it is possible to evaluate indication, clinical population selection, influence of clinical study covariates, disease phenotypes, and CD19 expression levels on clinical responses

Choice of Hyperparameters for Spike And Slab Prior, with Application to Dose Optimization in Oncology

This poster highlights the use of population pharmacokinetic and exposure-response models with regularized regression using spike and slab priors to optimize dosing for specific patient subpopulations, particularly focusing on the context of valemetostat treatment for Adult T-cell Leukemia / Lymphoma (ATTLL) and Non-Hodgkin’s lymphoma (NHL).

Towards the development of a platform PBPK-QSP model in the Julia programming language for evaluating potential toxicities caused by antibody-drug-conjugate therapies

Antibody-drug conjugates (ADCs) are promising anti-cancer drugs but often cause toxicities in clinical use. This poster presents a new model that predicts toxicities of ADCs, including liver and lung effects for drugs like T-DM1 and T-Dxd, and high hepatotoxicity in CM.

Open-Science Immuno-Oncology QSP Modeling Using Open-Source Julia Solvers

As Julia usage continues to grow within regulated biomedical environments, it is vital to ensure analyses are traceable and reproducible. Conducting analyses in an open-science manner is also critical to expand the adoption of Julia and to facilitate the infrastructure growth of Julia as an accessible ecosystem. A step-by-step model-building example of a classic monoclonal antibody-drug conjugate PBPK/tumor dynamics system illustrates how to develop such a reproducible open-science framework.

Open-Source Bayesian Hierarchical PBPK Modeling in Julia

Demonstrates a Bayesian analysis workflow in Julia for an ODE-based model using PBPK modeling as an illustrative example.

Training the next generation of pharmacometric modelers: a multisector perspective

The demand for pharmacometricians has outpaced academic supply, with increasing investments in on-the-job training. Despite growth in academic programs, the expanding scope of pharmacometrics and emerging fields like machine learning pose challenges. Leading experts from diverse sectors offer recommendations for effectively training future pharmacometricians, ensuring their ability to navigate this evolving discipline.

Population-Based Pharmacodynamic Modeling of Omalizumab in Pediatric Patients with Moderate to Severe Persistent Inadequately Controlled Allergic Asthma

The objective of this study was to quantitatively characterize the relationship between serum free IgE and pulmonary function (as measured by forced expiratory volume in 1 s [FEV1]) in pediatrics using a population-based pharmacodynamic model.

Exposure-Safety Markov Modeling of Ocular Adverse Events in Patient Populations Treated With Tisotumab Vedotin

The current analysis aimed to characterize exposure-response relationships of TV exposure on the incidence, severity, and longitudinal time course of grade ≥2 ocular adverse events (AEs).

Pharmacometrics-enhanced Bayesian borrowing for paediatric extrapolation – A case study of the DINAMO(TM) trial

DINAMO showed that an empagliflozin dosing regimen provided clinically and statistically meaningful reductions in HbA1c in youth with T2D. Bayesian Borrowing analysis confirmed evidence for clinically meaningful efficacy of empagliflozin

The combined use of propensity score matching and a joint tumor growth dynamics (TGD) – Overall Survival (OS) model to benchmark the efficacy of new treatments for advanced renal cell carcinoma (RCC)

The present work is to establish feasibility of using a joint tumor growth dynamic model (TGDOS) to extrapolate OS and generate a synthetic control arm from historical data by propensity score modeling.

Population pharmacokinetics, pharmacodynamics and pharmacogenetics modelling of oxypurinol in Hmong adults with gout and/or hyperuricemia

The aim of this study was to quantify identifiable sources of variability, including key pharmacogenetic variants in oxypurinol pharmacokinetics and their pharmacodynamic effect on serum urate (SU).

Investigating the contribution of residual unexplained variability components on bias and imprecision of parameter estimates in population pharmacokinetic mixed-effects modeling

The goal of this simulation-estimation study was to investigate the extent to which PK and RUV model misspecification, errors in recording dosing and sampling times, and variability in drug content uniformity contribute to the estimated magnitude of RUV and PK parameter bias.

Therapeutics Development in Polyarticular Course Juvenile Idiopathic Arthritis (pcJIA): Extrapolation, Dose Selection and Clinical Trial Design; Workshop Proceedings and Recent Updates

Stakeholders met to address persistent challenges facing development of therapeutics for polyarticular JIA (pJIA), which result in fewer approved therapies for children with pJIA than adults with rheumatoid arthritis (RA) and long lag times from adult RA approval to pediatric labeling.

Bayesian modeling workflow for pharmacometric applications using bbr.bayes with Stan/Torsten

Presented by Bill Gillespie at StanCon 2023, this workshop highlights how to leverage the R package bbr.bayes to create traceable and reproducible Bayesian modeling workflows. The current version of bbr.bayes supports Stan models using cmdstanr, and future releases will include support for Bayesian modeling with NONMEM.

An Introduction to Causal Inference for Pharmacometricians

Presented by Jim Rogers. This joint ASCPT + ISoP webinar explores the application of causal inference concepts in pharmacometrics. May 18, 2023

Application of Quantitative Modeling in the Optimization of Dosing Regimen for Oncology Drug Development

Shelly Wang presents a ProjectOptimus focused webinar focused on the use of MIDD in dose selection and optimization in oncology drug development. May 11, 2023.

Dosing Recommendation Based on the Effects of Different Meal Types on Pexidartinib Pharmacokinetics in Healthy Subjects: Implementation of Model-informed Drug Development Strategy

A comprehensive regulatory and industry review of modeling and simulation practices in oncology clinical drug development

Ana Ruiz-Garcia, Paul Baverel, Dean Bottino, Michael Dolton, Yan Feng, Ignacio González-García, Jaeyeon Kim, Seth Robey, Indrajeet Singh, David Turner, Shu-Pei Wu, Donghua Yin, Di Zhou, Hao Zhu, Peter Bonate. J Pharmacokinet Pharmacodyn. March, 4 2023

An Introduction to Bayesian Estimation in NONMEM

Tim Waterhouse. Presented at 12th Annual Indiana Clinical and Translational Sciences Institute (CTSI) Symposium on Disease and Therapeutic Response Modeling. February 23, 2023.

A Showcase of Open-Source Tools for Scalable, Reproducible Pharmacometrics Workflows

Sam Callisto, Tim Waterhouse. Presented at 12th Annual Indiana Clinical and Translational Sciences Institute (CTSI) Symposium on Disease and Therapeutic Response Modeling. February 23, 2023.

Longitudinal Exposure-Response Modeling of Multiple Indicators of Alzheimer’s Disease Progression

This study aimed to combine modeling techniques from psychometric research (e.g., item response theory) and pharmacometrics (e.g., hierarchical models) to describe the multivariate longitudinal disease progression for patients with mild-to-moderate Alzheimer’s disease.

Variable or variate? A conundrum in pharmacometrics exposure–response models

Ana-Marija Grisic, Karthik Venkatakrishnan, Jonathan French, Akash Khandelwal. CPT Pharmacometrics Syst Pharmacol.  December, 20 2022. doi:10.1002/psp4.12905

A Population Pharmacokinetic-Pharmacodynamic Model Evaluating Efficacy of Nalbuphine Extended-Release in Patients with Prurigo Nodularis

Rena Eudy-Byrne, Matthew Riggs, Amale Hawi, Thomas Sciascia, Shashank Rohatagi. Br J Clin Pharmacol. 2023.  doi:10.1111/bcp.15663

Bayesian PBPK Modeling using R/Stan/Torsten and Julia/SciML/Turing.jl

Ahmed Elmokadem, Yi Zhang, Timothy Knab, William R. Gillespie. CPT Pharmacometrics Syst Pharmacol.  January, 20 2023. doi:10.1002/psp4.12926

Shrinkage in Population PK/PKPD Analysis

Sonoko Kawakatsu. Virtual presentation for Children’s Hospital of Philadelphia and Cincinnati’s Children’s Hospital. 13 December 2022.

Landmark and longitudinal exposure-response analyses for multiple efficacy and safety endpoints to justify the clinical dose of valemetostat for adult T-cell leukemia/lymphoma

Masato Fukae, Kyle Baron, James Rogers, Ramon Garcia, Masaya Tachibana, John Mondick, Takako Shimizu. Poster presented at 2022 American Conference on Pharmacometrics (ACoP13). 30 October – November 2 2022. Poster M-026

Simultaneous population pharmacokinetic analysis of total and unbound valemetostat in patients with non Hodgkin lymphoma to quantify the effect of the binding protein, alpha 1 acid glycoprotein

Masato Fukae, Kyle Baron, Masaya Tachibana, John Mondick, Takako Shimizu. Poster presented at 2022 American Conference on Pharmacometrics (ACoP13). 30 October – November 2 2022. Poster M-030

Emerging use of real-world data to address data gaps in clinical pharmacology: Opportunities and challenges

Simon Dagenais, Marc Gastonguay, Abie Ekangaki. Hot topic presented at 2022 AAPS PharmSci360. 17 October 2022.

An Introduction to Causal Inference for Pharmacometricians

James Rogers, Hugo Maas, Alejandro Perez PitarchCPT Pharmacometrics Syst Pharmacol.  November, 16 2022. doi:10.1002/psp4.12894

Disease Trajectory of SLE Clinical Endpoints and Covariates Affecting Disease Severity and Probability of Response: Analysis of Pooled Patient-Level Placebo (Standard-of-Care) Data to Enable Model-Informed Drug Development

Kosalaram Goteti, Jonathan French, Ramon Garcia, Ying Li, Florence Casset-Semanaz, Aida Aydemir, Robert Townsend, Cristina Vazquez Mateo, Matthew Studham, Oliver Guenther, Amy Kao, Marc Gastonguay, Pascal Girard, Lisa Benincosa, Karthik Venkatakrishnan. CPT Pharmacometrics Syst Pharmacol.  November, 9 2022. doi:10.1002/psp4.12888

Impact of Drug Exposure on Resistance Selection Following Artemether-Lumefantrine Treatment for Malaria in Children With and Without HIV in Uganda

Katherine Kay, Justin Goodwin, Hanna Ehrlich, Joyce Ou, Tracey Freeman, Kaicheng Wang, Fangyong Li, Martina Wade, Jonathan French, Liusheng Huang, Francesca Aweeka, Norah Mwebaza, Richard Kajubi, Matthew Riggs, Ana Ruiz-Garcia, Sunil Parikh. Clin Pharmacol Ther. Published online October 19, 2022. doi:10.1002/cpt.2768

Application of Model-Based Meta-Analysis to Set Benchmarks for New Treatments of Systemic Lupus Erythematosus

Kosalaram Goteti, Ramon Garcia, William Gillespie, Jonathan French, Lena Klopp-Schulze, Ying Li, Cristina Vazquez Mateo, Sanjeev Roy, Oliver Guenther, Lisa Benincosa, Karthik Venkatakrishnan. Poster presented at 2022 American Conference on Pharmacometrics (ACoP13). 30 October – November 2 2022. Poster T-075

Association of lumefantrine pharmacokinetics and resistance selection following artemether-lumefantrine treatment in children with and without HIV in Uganda

Katherine Kay, Justin Goodwin, Hanna Ehrlich, Joyce Ou, Tracy Freeman, Kaicheng Wang, Fangyong Li, Martina Wade, Jonathan French, Liusheng Huang, Francesca T. Aweeka, Norah Mwebaza, Richard Kajubi, Matthew Riggs, Ana Ruiz-Garcia, Sunil Parikh. Poster presented at American Society of Tropical Medicine and Hygiene (ASTMH). October 30 – November 3, 2022. Poster #1434.

Pharmacometrics Golems: Exposure-Response Models in Oncology

Akash Khandelwal, Ana-Marija Grisic, Jonathan French, Karthik Venkatakrishnan. Clin Pharmacol Ther. Published online March 14, 2022. doi:10.1002/cpt.2564

A showcase of open-source tools for scalable, reproducible PMx workflows

Kyle Baron, Sam Callisto, Seth Green, Matthew Riggs. A showcase of open-source tools for scalable, reproducible PMx workflows. Pre Meeting Workshop presented at 2022 American Conference on Pharmacometrics (ACoP13). 30 October 2022.

Disease Trajectory modeling of SLE clinical endpoints using a Latent Variable Model: Analysis of Pooled Patient-Level Placebo (Standard-of-Care) Data

Kosalaram Goteti, Jonathan French, Ramon Garcia, Ying Li, Florence Casset-Semanaz, Aida Aydemir, Robert Townsend, Cristina Vazquez Mateo, Matthew Studham, Oliver Gunther, Amy Kao, Marc Gastonguay, Pascal Girard, Lisa Benincosa, Karthik Venkatakrishnan. Poster presented at 12th American Conference on Pharmacometrics (ACoP), November 2021. Poster PIB-011.

Bayesian PBPK Modeling using R/Stan/Torsten and Julia/SciML/Turing.jl

Ahmed Elmokadem, Yi Zhang, Tim Knab, Eric Jordie, William R. Gillespie. Poster presented at 2022 American Conference on Pharmacometrics (ACoP13). 30 October – November 2 2022. Poster W-074

A Population Pharmacokinetic Model and Exposure-Response Model of Repeated Time Event (RTTE) to Justify a Dose Increase in Patients with Sickle Cell Disease

Rena Byrne, Rahul Ballal, Ana Ruiz-Garcia. Poster presented at 2022 American Conference on Pharmacometrics (ACoP13). 30 October – November 2 2022. Poster T-016

Analysis Planning and Interpretation Using Causal Directed Acyclic Graphs: A Case Study in Oncology

James A. Rogers, Hugo Maas, Alejandro Peréz. Poster presented at 2022 American Conference on Pharmacometrics (ACoP13). 30 October – November 2 2022. Poster T-022

A Suite of Open-Source Tools to Guide Efficient Pharmacometric Analyses

Katherine Kay, Kyle Baron, Seth Green, Samuel Callisto, Curtis Johnston, Kyle Barrett, Devin Pastoor, Jim Rogers, Ana Ruiz-Garcia, Tim Waterhouse, Matthew Wiens, Matthew Riggs. Poster presented at 2022 American Conference on Pharmacometrics (ACoP13). 30 October – November 2 2022. Poster M-062

A Machine Learning and Statistical Meta-Analysis for Trial Simulations Predicting Transitions from Relapsing-Remitting to Secondary Progressive Multiple Sclerosis

Matthew Wiens, Kyle Barrett, Amir-Hadi Maghzi, Jonathan French, Himanshu Naik, Jackson Burton. Poster presented at 2022 American Conference on Pharmacometrics (ACoP13). 30 October – November 2 2022. Poster M-055

A Model-Based Meta-Analysis for Treatment-Modified Disease Progression in Multiple Sclerosis.

Matthew Wiens, Amir-Hadi Maghzi, Naveen Mangal, Kumar Kandadi Muralidharan, Francois Gaudreault, Jackson Burton, Jonathan French, Himanshu Naik. Poster presented at 2022 American Conference on Pharmacometrics (ACoP13). 30 October – November 2 2022. Poster M-053

Using Graphical Models and Causal Thinking to Inform Pharmacometric Modeling

Jonathan French. Presented at Bayes 2022. 12 – 14 October 2022.

Using Quarto to showcase an ecosystem of open-source R packages for Pharmacometrics

Seth Green. Presented at R/Medicine 2022. 26 August 2022.

Landscape analysis for a neonatal disease progression model of bronchopulmonary dysplasia: Leveraging clinical trial experience and real-world data

Jeffrey S. Barrett, Megan Cala Pane, Timothy Knab, William Roddy, Jack Beusmans, Eric Jordie, Kanwaljit Singh, Jonathan Michael Davis, Klaus Romero, Michael Padula, Bernard Thebaud, Mark Turner. Front. Pharmacol. 2022 October 12. doi: 10.3389/fphar.2022.988974

Impact of drug exposure on resistance selection following artemether-lumefantrine treatment for malaria in children with and without HIV in Uganda

Katherine Kay, Justin Goodwin, Hanna Ehrlich, Joyce Ou, Tracey Freeman, Kaicheng Wang, Fangyong Li, Martina Wade, Jonathan French, Liusheng Huang, Francesca Aweeka, Norah Mwebaza, Richard Kajubi, Matthew Riggs, Ana Ruiz-Garcia, Sunil Parikh. Clin Pharmacol Ther. Published online October 19, 2022. doi:10.1111/cpt.2768

Extrapolation of Efficacy of a Dextroamphetamine Transdermal System from Pediatric to Adult Populations Using Pharmacokinetic Modeling.

Mariacristina Castelli, Katsumi Suzuki, Brittney Starling, Kanan Balakrishnan, Suzanne Meeves, Marina Komaroff, Janelle Lennie, John T. Mondick, Stephen V. Faraone.
Presented at the American Society of Clinical Psychopharmacology Annual Meeting, May 31–June 3, 2022, in Scottsdale, AZ. Poster #W2

Pharmacokinetic Modeling of Warfarin ІI – Model-based Analysis of Warfarin Metabolites following Warfarin Administered either Alone or Together with Fluconazole or Rifampin

Shen ChengDarcy R FloraAllan E. RettieRichard C. Brundage and Timothy S. Tracy.

Pharmacokinetics of vaginal versus buccal misoprostol for labor induction at term

Yana VorontsovaDavid M. HaasKathleen FlanneryAndrea R. MastersLarissa L. SilvaRebecca C. PiersonBrittany YeleyGraham HoggDavid GuiseMichael HeathmanSara K. Quinney. Clin Transl Sci2022001– 9. doi:10.1111/cts.13306

Flexible and efficient Bayesian pharmacometrics modeling using Stan and Torsten, Part I

Charles C. Margossian, Yi Zhang, William R. Gillespie. Flexible and efficient Bayesian pharmacometrics modeling using Stan and Torsten, Part I. CPT Pharmacometrics Syst Pharmacol. 2022 May 15. doi: 10.1002/psp4.12812. Epub ahead of print. PMID: 35570331.

Bayesian modeling and simulation to inform rare disease drug development early decision-making: Application to Duchenne muscular dystrophy

Janelle L. Lennie, John T. Mondick, Marc R. Gastonguay. PLoS One. 2022 Apr 28;17(4):e0247286. doi: 10.1371/journal.pone.0247286.

A Pharmacokinetic Analysis of Tobramycin in Patients Less than Five Years of Age with Cystic Fibrosis: Assessment of Target Attainment with Extended-Interval Dosing through Simulation

Kevin J. Downes, Austyn Grim, Laura Shanley, Ronald C. Rubenstein, Athena F. Zuppa, Marc R. Gastonguay. Antimicrob Agents Chemother. 2022;66(5):e0237721.

An Empirical Approach to Identifying Electrophysiological Correlates of Topiramate-Related Working Memory Impairment Using Pharmacokinetic-Pharmacodynamic Modeling

Samuel P. Callisto, Christopher M. Barkley, Mark Fiecas, Richard Brundage, Angela K. Birnbaum, Susan E. Marino. Poster presented at 2022 WCOP. March 29 – April 1 2022. Poster 35.

Pharmacometrics Golems: Exposure-Response Models in Oncology

Akash KhandelwalAna-Marija GrisicJonathan FrenchKarthik Venkatakrishnan. Clin Pharmacol Ther. Published online March 14, 2022. doi:10.1002/cpt.2564

A model-based analysis to guide gonadotropin-releasing hormone receptor antagonist use for management of endometriosis

Pohl OBaron KRiggs MFrench JGarcia RGotteland JPBr J Clin Pharmacol20211– 13. doi:10.1111/bcp.15171

Pharmacometric modeling and machine learning analyses of prognostic and predictive factors in the JAVELIN Gastric 100 phase III trial of avelumab

Nadia TerranovaJonathan FrenchHaiqing DaiMatthew WiensAkash KhandelwalAna Ruiz-GarciaJuliane ManitzAnja von HeydebreckMary RuisiKevin ChinPascal GirardKarthik Venkatakrishnan. CPT Pharmacometrics Syst Pharmacol. 2022;11(3):333-347.

Pharmacometric modeling and machine learning analyses of prognostic and predictive factors in the JAVELIN Gastric 100 phase III trial of avelumab

Terranova NFrench JDai H, et al. CPT Pharmacometrics Syst Pharmacol2022001– 15. doi:10.1002/psp4.12754

Modeling Reaction Time Distributions Increases the Statistical Power of Cognition Testing

Seth C. Hopkins, Sean D. Wilson, Ajay Ogirala, Gabriel Stellman, Snezana M. Milanovic, Steven T. Szabo, James A. Rogers, Chris J. Edgar, Kenneth S. Koblan. Poster presented at 2021 American College of Neuropsychopharmacology. 5-8 December 2021.

I’m a Bayesian and I’m OK: Or How I Learned to Stop Worrying and Love Variability and Uncertainty

William R. Gillespie. The Lewis B. Sheiner Lecturer Award slides presented at International Society of Pharmacometrics. November 2021.

A Torsten case study: Evaluating the benefits of cross-chain communication during the warmup phase of Hamiltonian Monte Carlo (HMC) simulation

Yi Zhang and William R. Gillespie. Poster presented at 2021 American Conference on Pharmacometrics (ACoP12) virtual meeting. 8-12 November 2021. Poster PIIIB-028

Quantitative Understanding of the Longitudinal Relationship between Short-term MRI Outcomes and Long-term Clinical Outcomes Measures in Multiple Sclerosis

Matthew Wiens, Amir-Hadi Maghzi, Naveen Mangal, Kumar Kandadi Muralidharan, Himanshu Naik, Jonathan French, Francois Gaudreault. Poster presented at 2021 American Conference on Pharmacometrics (ACoP12) virtual meeting. 8-13 November 2021. Poster PIIIB-009.

Exposure-response analysis of efficacy and safety for pexidartinib in patients with tenosynovial giant cell tumor (TGCT)

Yin O, Zahir H, French J, Polhamus D, Wang X, Van de Sande M, Tap WD, Gelderblom H, Wagner AJ, Healey JH, Greenberg J, Shuster D, Stacchiotti S. CPT: Pharmacometrics & Systems Pharmacology. 2021101422– 1432. doi:10.1002/psp4.12712

Simplified models to assess newborn gestational age in low-middle income countries: findings from a multicountry, prospective cohort study

Alliance for Maternal and Newborn Health Improvement (AMANHI) Gestational Age Study Group, & Alliance for Maternal and Newborn Health Improvement (AMANHI) GA Study Group. BMJ Global Health. 2021;6(9):e005688. https://doi.org/10.1136/bmjgh-2021-005688

Development and validation of open-source pharmacometrics software using an iterative software development life cycle methodology: the pmtables R package for submission-ready table generation

Kyle T. Baron, Devin Pastoor, Anna Nevison, Katherine Kay, Marc R. Gastonguay. Poster presented at Population Approach Group Europe Annual Meeting; 2-3 and 6-7 September 2021.  Poster III-02.

A physiologically-based pharmacokinetic modeling approach to support candidate and first in human dose selection for bamlanivimab

Tim Knab, Ahmed Elmokadem, Emmanuel Chigutsa, Eric Jordie, Matthew Riggs, Patricia Brown-Augsburger, Christopher Wiethoff, Ajay Nirula, Jenny Y Chien, Lisa O’Brien.  Poster presented at Population Approach Group Europe Annual Meeting; 2-3 and 6-7 September 2021.  Poster I-64.

Torsten: Stan functions for pharmacometric applications – Improvements and new R interface workflow

Yi Zhang and William R. Gillespie.  Poster presented at Population Approach Group Europe Annual Meeting; 2-3 and 6-7 September 2021.  Poster I-61.

Dosing regimen optimisation for oseltamivir in immunocompromised paediatric patients with influenza: Extrapolation of efficacy

Jordie EB, Gibiansky L, Knab T, Lemenuel-Diot A, Ravva P, Zwanziger E, Jolivet S, Bhardwaj R, Hernández-Sánchez J, Nasmyth-Miller C, Sturm S. Br J Clin Pharmacol. 2021;1-13. doi:10.1111/bcp.15059

Pharmacokinetic modeling of R and S-Methadone and their metabolites to study the effects of various covariates in post-operative children

Aruldhas BW, Quinney SK, Overholser BR, Heathman MA, Masters AR, Ly RC, Gao H, Packiasabapathy S, Sadhasivam S. CPT Pharmacometrics Syst Pharmacol2021001– 12. doi:10.1002/psp4.12687

Population pharmacokinetic and exposure–efficacy analysis of ixekizumab in paediatric patients with moderate-to-severe plaque psoriasis (IXORA-PEDS)

Jackson K, Chua L, Velez de Mendizabal N, Pitou C, Rodriguez Capriles C, Paller AS, Lansang P, Seyger M, Papp K, IXORA-PEDS study group. Br J Clin Pharmacol20211– 13. doi:10.1111/bcp.15034

Impact of Obesity on Brexpiprazole Pharmacokinetics: Proposal for Improved Initiation of Treatment

Bruno CD, Elmokadem A, Housand C, Jordie EB, Chow CR, Laughren T, Greenblatt DJ. Journal of Clinical Pharmacology.  2021;62(1):55-65. doi:10.1002/jcph.1947

Brexpiprazole Pharmacokinetics in CYP2D6 Poor Metabolizers: Using Physiologically Based Pharmacokinetic Modeling to Optimize Time to Effective Concentrations

Elmokadem A, Bruno CD, Housand C, Jordie EB, Chow CR, Lesko LJ, Greenblatt DJ.  J Exp Pharmacol20211– 10. doi:10.1002/jcph.1946

Population pharmacokinetic analysis of ulotaront in subjects with schizophrenia

Galluppi GR, Polhamus DG, Fisher JM, Hopkins SC, Koblan KS. CPT Pharmacometrics Syst Pharmacol. Published online July 22, 2021. doi:10.1002/psp4.12692

Exposure-response modeling of the effect of glasdegib on cardiac repolarization in patients with cancer

Fostvedt LK, Shaik N, Martinelli G, Wagner AJ, Ruiz-Garcia A. Expert Rev Clin Pharmacol. 2021 Jul;14(7):927-935. doi: 10.1080/17512433.2021.1925538. Epub 2021 May 18.

Should Deep-Sequenced Amplicons Become the New Gold Standard for Analyzing Malaria Drug Clinical Trials?

Jones S, Kay K, Hodel EM, Gruenberg M, Lerch A, Felger I, Hastings I. Antimicrobial Agents and Chemotherapy. 2021;65(10), e0043721. doi:10.1128/AAC.00437-21

CPT: Pharmacometrics & Systems Pharmacology – Inception, Maturation, and Future Vision.

Rowland Yeo K, Hennig S, Krishnaswami S, Strydom N, Ayyar VS, French J, Sinha V, Sobie E, Zhao P, Friberg LE, Mentré F.
CPT Pharmacometrics Syst Pharmacol. 2021 Jul;10(7):649-657. doi: 10.1002/psp4.12680.

A Modeling and Simulation Primer for the Design of Pediatric Pharmacokinetic Studies

John T. Mondick and Curtis K. Johnston.  Webinar presented for American Society for Clinical Pharmacology and Therapeutics (ASCPT).  June 22, 2021.

Pharmacometric Dose Optimization of Buprenorphine in Neonatal Opioid Withdrawal Syndrome

Eudy-Byrne R, Zane N, Adeniyi-Jones SC, Gastonguay MR, Ruiz-Garcia A, Kushal G, Kraft WK. Clin Transl Sci. 2021;14:2171-2183. doi:10.1111/cts.13074

Welcome to the statistics and pharmacometrics themed issue

French J, Mentré, F. CPT Pharmacometrics Syst. Pharmacol. 2021;10: 273-274. doi:10.1002/psp4.12625

Lorlatinib Exposure-Response Analyses for Safety and Efficacy in a Phase I/II Trial to Support Benefit-Risk Assessment in Non-Small Cell Lung Cancer

Chen J, Ruiz-Garcia A, James LP, et al. Clin Pharmacol Ther. 2021;110(5):1273-1281. doi:10.1002/cpt.2228

Decision making in drug development: An opportunity for model-based knowledge integration and scenario evaluation.

Seminar presented by Marc R. Gastonguay, Ph.D., at the FDA’s Model Informed Drug Development (MIDD) Education Series, April 26, 2021 (virtual).

Postprandial triglyceride reduction following acute treatment of a selective 5-hydroxytryptamine-2c agonist and characterization using a semi-physiological model.

Leohr J, Heathman M, Kjellsson MC. Diabetes Obes Metab. 2021 Apr;23(4):1001-1010. doi: 10.1111/dom.14306.

A Model-Informed Drug Development (MIDD) Approach for a Low Dose of Empagliflozin in Patients with Type 1 Diabetes

Johnston CK, Eudy-Byrne RJ, Elmokadem A, Nock V, Marquard J, Soleymanlou N, Riggs MM, Liesenfeld K-H. Pharmaceutics. 2021; 13(4):485. https://doi.org/10.3390/pharmaceutics13040485

Pharmacokinetic and Pharmacodynamic Target Attainment in Adult and Pediatric Patients Following Administration of Ceftaroline Fosamil as a 5-Minute Infusion

 

Riccobene TA, Carrothers TJ, Knebel W, Raber S, Chan PLS. Clin Pharmacol Drug Dev. 2021 Apr;10(4):420-427. doi: 10.1002/cpdd.907.

Opportunities at the Intersection of Pharmacometrics and Health Economics for Insightful Drug Development Decision Making

Marc Gastonguay, Jing Liu, Jean Lachaine, Anna G. Kondic, and Daniel Polhamus.  Presented at the American Society for Clinical Pharmacology (ASCPT) annual meeting, March 15, 2021.

Theory, Empiricism, Certain Random Events, and a Vision for the Continued Growth of Pharmacometrics

Presentation by Marc Gastonguay for the ASCPT Sheiner-Beal Award during the American Society for Clinical Pharmacology (ASCPT) annual meeting, March 11, 2021.

Population pharmacokinetic model with time-varying clearance for lorlatinib using pooled data from patients with non-small cell lung cancer and healthy participants

Chen J, Houk B, Pithavala YK, Ruiz-Garcia A. CPT Pharmacometrics Syst Pharmacol. 2021 Feb;10(2):148-160. doi: 10.1002/psp4.12585. Epub 2021 Feb 1.

Population pharmacokinetics of vedolizumab in Asian and non-Asian patients with ulcerative colitis and Crohn’s disease.

Okamoto H, Dirks NL, Rosario M, Hori T, Hibi T. Intest Res. 2021;19(1):95-105. doi:10.5217/ir.2019.09167.

Characterization of the Relationship of Inotuzumab Ozogamicin Exposure With Efficacy and Safety End Points in Adults With Relapsed or Refractory Acute Lymphoblastic Leukemia

Chen J, Haughey M, Vandendries E, DeAngelo DJ, Kantarjian HM, Ruiz-Garcia A. Clin Transl Sci. 2021 Jan;14(1):184-193. doi: 10.1111/cts.12841. Epub 2020 Aug 18.

Complex genetic dependencies among growth and neurological phenotypes in healthy children: Towards deciphering developmental mechanisms

Uechi L, Jalali M, Wilbur JD, French JL, Jumbe NL, Meaney MJ, Gluckman PD, Karnani N, Sakhanenko NA, Galas DJ; GUSTO study group. PLoS One. 2020 Dec 3;15(12):e0242684. doi: 10.1371/journal.pone.0242684.

Incorporating genetic selection into individual‐based models of malaria and other infectious diseases

Hastings, IMHardy, DKay, KSharma, REvol Appl2020132723– 2739https://doi.org/10.1111/eva.13077

Modeling and simulation of lumefantrine pharmacokinetics in HIV-infected and HIV-uninfected children with malaria and the role of lumefantrine exposure as a potential driver of drug resistance

Kay K, Goodwin J, Mwebaza N, Ruiz A, Ehrlich H, Ou J, Freeman T, Wade M, Huang L, Wang K, Li F, Aweeka FT, Riggs M, Kajubi R, Parikh S.  Presented at the annual meeting of the American Society of Tropical Medicine and Hygiene, October 16-18, 2020.

Population pharmacokinetics of adalimumab biosimilar adalimumab-adbm and reference product in healthy subjects and patients with rheumatoid arthritis to assess pharmacokinetic similarity.

Kang J, Eudy-Byrne RJ, Mondick J, Knebel W, Jayadeva G, Liesenfeld KH. Br J Clin Pharmacol. 2020 Nov;86(11):2274-2285. doi: 10.1111/bcp.14330.

Applications and Opportunities at the Intersection of Pharmacometrics, Health Economics, Outcomes Research, and Real-World Evidence

Presentation by Marc R. Gastonguay, Ph.D., at the Otago Pharmacometrics International Seminar Series on November 10, 2020.

Development and evaluation of a predictive model of hyperphosphatemia induced by inhibition of FGFR by extending an existing multiscale systems pharmacology

Matthew M. Riggs, Howard A. Ball, Kanji Komatsu, Akihiro Yamada.  Poster presented at 2020 American Conference on Pharmacometrics (ACoP11) virtual meeting. 10 November 2020.

Model code and supporting material is available here.

Speed up population Bayesian inference by combining cross-chain warmup and within-chain parallelization

Yi Zhang, William R. Gillespie, Ben Bales, Aki Vehtari.  Poster presented at 2020 American Conference on Pharmacometrics (ACoP11) virtual meeting. 11 November 2020.

 

Comparison of TGD-OS models with a long-term surviving fraction

Ramon I. Garcia, Seth Robey, Pavan Vaddady, Lokesh Jain, Jonathan L French.  Poster presented at 2020 American Conference on Pharmacometrics (ACoP11) virtual meeting. 12 November 2020.

 

Improving strategic decision-making with early prediction of survival outcomes in oncology clinical trials

Presentation by Jonathan L. French, Sc.D. at 2020 American Conference on Pharmacometrics (ACoP11) virtual meeting. 11 November 2020.

Markov models at the intersection of pharmacometrics and health economics

Presentation by Marc Gastonguay, Ph.D. at 2020 American Conference on Pharmacometrics (ACoP11) virtual meeting. 11 November 2020.

An evaluation of overall survival in patients with newly diagnosed acute myeloid leukemia and the relationship with glasdegib treatment and exposure

Lin S, Shaik N, Chan G, Cortes JE, Ruiz-Garcia A. Cancer Chemother Pharmacol. 2020 Oct;86(4):451-459. doi: 10.1007/s00280-020-04132-x. Epub 2020 Sep 3.

The use of exposure-response with therapeutic proteins in pediatric drug development

Presentation by Marc Gastonguay, Ph.D., at the 2020 Virtual Annual Meeting of the American College of Clinical Pharmacology (ACCP) during the symposium: Innovative Approaches in the Use of Exposure-Response in Therapeutic Proteins to Support Pediatric Extrapolation. 23 September 2020.

Quantification of the Impact of Partition Coefficient Prediction Methods on PBPK Model Output Using a Standardized Tissue Composition

Utsey, Kiersten, Madeleine S. Gastonguay, Sean Russell, Reed Freling, Matthew M. Riggs, and Ahmed Elmokadem. 2020. Drug Metabolism and Disposition: The Biological Fate of Chemicals, July. https://doi.org/10.1124/dmd.120.090498.

Pharmacokinetic Modeling of Intrathecally Administered Recombinant Human Arylsulfatase A (TAK‐611) in Children With Metachromatic Leukodystrophy

Troy S, Wasilewski M, Beusmans J, Godfrey CJ.  Clin Pharmacol Ther. 2020 Jun;107(6):1394-1404. doi: 10.1002/cpt.1752. Epub 2020 Feb 25. PMID: 31868225; PMCID: PMC7325319.

Phase 1 study to evaluate the effect of the investigational anticancer agent sapanisertib on the QTc interval in patients with advanced solid tumors

Patel, Chirag, Sanjay Goel, Manish R. Patel, Lakshmi Rangachari, Jayson D. Wilbur, Yaping Shou, Karthik Venkatakrishnan, and A. Craig Lockhart. Clinical Pharmacology in Drug Development, June 2020.

Simplified models to assess gestational age in low-middle income countries: Findings from the multi-site AMANHI study

A.C. Lee, K.E. Semrau, B. Wylie, A.H. Baqui, B. Kirkwood, A.A. Manu, F. Jehan, M. Nisar, S. Sazawal, U. Dhingra, D.H. Hamer, J.D. Wilbur, S. Yoshida, R. Bahl.  Simplified Models to Assess Gestational Age in Low-Middle Income Countries: Findings from the Multi-site AMANHI Study.  Pediatric Academic Societies Meeting, May 2, 2020. E-PAS2020:1555.6

Pharmacokinetic Models to Characterize the Absorption Phase and the Influence of a Proton Pump Inhibitor on the Overall Exposure of Dacomitinib

Ruiz-Garcia A, Tan W, Li J, Haughey M, Masters J, Hibma J, Lin S. Pharmaceutics. 2020 Apr 7;12(4):330. doi: 10.3390/pharmaceutics12040330.

MID3: Mission Impossible or Model‐Informed Drug Discovery and Development? Point‐Counterpoint Discussions on Key Challenges

Krishnaswami, S., Austin, D., Della Pasqua, O., Gastonguay, M.R., Gobburu, J., van der Graaf, P.H., Ouellet, D., Tannenbaum, S. and Visser, S.A.G. (2020), MID3: Mission Impossible or Model‐Informed Drug Discovery and Development? Point‐Counterpoint Discussions on Key Challenges. Clin. Pharmacol. Ther., 107: 762-772. doi:10.1002/cpt.1788

 

Latent process model of the 6-minute walk test in Duchenne muscular dystrophy

Lennie, J.L., Mondick, J.T. & Gastonguay, M.R. Latent process model of the 6-minute walk test in Duchenne muscular dystrophy. J Pharmacokinet Pharmacodyn (2020).

MID3: Mission Impossible or Model‐Informed Drug Discovery and Development? Point‐Counterpoint Discussions on Key Challenges

Krishnaswami, S., Austin, D., Della Pasqua, O., Gastonguay, M.R., Gobburu, J., van der Graaf, P.H., Ouellet, D., Tannenbaum, S. and Visser, S.A. (2020), MID3: Mission Impossible or Model‐Informed Drug Discovery and Development? Point‐Counterpoint Discussions on Key Challenges. Clin. Pharmacol. Ther. Accepted Author Manuscript. doi:10.1002/cpt.1788

Low-Dose Empagliflozin as Adjunct-to-Insulin Therapy in Type 1 Diabetes: A Valid Modeling and Simulation Analysis to Confirm Efficacy

Perkins BA, Soleymanlou N, Rosenstock J, Skyler JS, Laffel LM, Liesenfeld KH, Neubacher D, Riggs MM, Johnston CK, Eudy-Byrne RJ, Elmokadem A, George JT, Marquard J, Nock V.  Diabetes, Obesity & Metabolism, 2019 Dec 19. Available from: https://doi.org/10.1111/dom.13945.

Toward Progress in Quantitative Translational Medicine: A Call to Action

Venkatakrishnan, Karthik, Songmao Zheng, Cynthia J. Musante, Jin Y. Jin, Matthew M. Riggs, Sriram Krishnaswami, and Sandra A. G. Visser. 2020. “Toward Progress in Quantitative Translational Medicine: A Call to Action.” Clinical Pharmacology and Therapeutics 107 (1): 85–88.  Available from: https://doi.org/10.1002/cpt.1687

Quantitative Systems Pharmacology and Physiologically Based Pharmacokinetic Modeling With mrgsolve: A Hands-On Tutorial

Elmokadem, A., Riggs, M. M. and Baron, K. T. (2019), Quantitative Systems Pharmacology and Physiologically‐Based Pharmacokinetic Modeling With mrgsolve: A Hands‐On Tutorial. CPT Pharmacometrics Syst. (2019) 8, 883–893.  Available from: https://doi.org/10.1002/psp4.12467

Population Pharmacokinetic Analysis for Comparison of Pexidartinib Exposure in Asian and Non-Asian Patients

Chia-Chi Lin, Jun Guo, William D. Tap, Andrew J. Wagner, Silvia Stacchiotti, Jih-Hsiang Lee, Xiaoning Wang, Jia Kang, Hamim Zahir, Shun-ichi Sasaki, Ophelia Yin

Poster presented at the 2019 Connective Tissue Oncology Society annual meeting in Toyko, Japan. 14 Nov 2019

The confluence of Statistical and Pharmacometric Approaches for Benefit Risk Analysis: a case study using Bayesian joint models for safety and efficacy

Presented by Jonathan French, Sc.D., at the American Conference on Pharmacometrics (ACoP10) during the tutorial: The Role of Pharmacometrics in Advancing Quantitative Benefit-Risk Assessments for Drug Review and Approval. 24 Oct 2019

Impact of Partition Coefficient Prediction Methods on PBPK Model Output Using a Unified Tissue Composition

Kiersten Utsey, Madeleine S Gastonguay, Sean Russell, Reed Freling, Matthew M Riggs, Ahmed Elmokadem

Poster presented at 2019 American Conference on Pharmacometrics (ACoP10) in Orlando, FL. 22 October 2019.

A completely open-source pharmacometrics tool set: Moving from vision to reality with R, mrgsolve and Stan/Torsten

Presentation by Marc Gastonguay, Ph.D. and William Gillespie, Ph.D., at 2019 American Conference on Pharmacometrics (ACoP10) in Orlando, FL during the tutorial: Pharmacometrics Goes Open-Source. 24 October 2019.

Exposure-Response Analysis of Efficacy and Safety for Pexidartinib in Patients With Tenosynovial Giant Cell Tumor (TGCT)

Ophelia Yin, Jonathan French, Daniel Polhamus, Hamim Zahir, Michiel van de Sande, William D. Tap, Hans Gelderblom, Andrew J. Wagner, Jon Greenberg, Dale Shuster, Silvia Stacchiotti

Poster presented at 2019 American Conference on Pharmacometrics (ACoP10) in Orlando, FL. 23 October 2019.

A Semi-physiological Population Pharmacokinetic Model Developed Using Clinical Dose Escalation and Dose Confirmation Data for an Oral Fixed-Dose Combination of CDA Inhibitor Cedazuridine with Decitabine (ASTX727) in Subjects with Myelodysplastic Syndromes

Eric Burroughs Jordie, Ahmed Elmokadem, Mohammad Azab, and Aram Oganesian

Presented by Eric Jordie at American Conference on Pharmacometrics 2019.

Considerations and Future Directions for the Development of Open-Source, Public License, Pharmacometric Software

Presentation by Marc Gastonguay, Ph.D. at 2019 American Conference on Pharmacometrics (ACoP10) in Orlando, FL. 21 October 2019.

Considerations for Assuring Quality Tools and a Proposal for Open Software Development Standards

Presentation by Marc Gastonguay, Ph.D. at 2019 American Conference on Pharmacometrics (ACoP10) in Orlando, FL. 20 October 2019.

Model-based Dose Selection for a GnRH Receptor Antagonist in Endometriosis and Uterine Fibroids (UF) to Reduce Symptoms While Preventing Lumbar Spine Bone Mineral Density (BMD) Loss (slide deck)

Presentation by Kyle Baron, PharmD, Ph.D., at the American Conference of Pharmacometrics in October 2019. Poster can be found here.
Authors: Kyle Baron, Oliver Pohl, Matthew Riggs, Jonathan French, Jean-Pierre Gotteland, Ramon Garcia

Model-based Dose Selection for a GnRH Receptor Antagonist in Endometriosis and Uterine Fibroids (UF) to Reduce Symptoms While Preventing Lumbar Spine Bone Mineral Density (BMD) Loss (poster)

Poster presented at the American Conference of Pharmacometrics in October 2019. Accompanying slides can be found here.
Authors: Kyle Baron, Oliver Pohl, Matthew Riggs, Jonathan French, Jean-Pierre Gotteland, Ramon Garcia

Population Pharmacokinetic Analysis of Pexidartinib in Healthy Subjects and Patients with Tenosynovial Giant Cell Tumor (TGCT) or Other Solid Tumors

Ophelia Yin, Jia Kang, William Knebel, Hamim Zahir, Michiel van de Sande, William D. Tap, Hans Gelderblom, Silvia Stacchiotti, Jon Greenberg, Dale Shuster, Andrew J. Wagner

Poster presented at 2019 American Conference on Pharmacometrics (ACoP10) in Orlando, FL. 21 October 2019.

Bridging Knowledge Gaps in PBPK through Open Science

Presented by Marc Gastonguay, Ph.D at Development of Best Practices in Physiologically Based Pharmacokinetic Modeling to Support Clinical Pharmacology Regulatory Decision -Making Sponsored by the Office of Clinical Pharmacology OTS, CDER, U.S. Food and Drug Administration (FDA) on 18 November 2019. Event information here. Slides are here

Transparent, Open and Reproducible PBPK and QSP Modeling and Simulation Using an R-Based Framework

Presented by Ahmed Elmokadem, Ph.D at the 9th Annual CTSI Disease and Therapeutic Response Modeling and Simulation Symposium at Indiana University School of Medicine on November 12, 2019. Event details can be found here.

The use of modeling & simulation to facilitate an understanding of pediatric dose-exposure-response for small molecules and biologics

Presented by Marc Gastonguay, Ph.D. at the DIA Pediatric Drug Development Workshop on October 28, 2019. Event details on the DIA website.

Open Systems Pharmacology Community—An Open Access, Open Source, Open Science Approach to Modeling and Simulation in Pharmaceutical Sciences

Lippert, J. , Burghaus, R. , Edginton, A. , Frechen, S. , Karlsson, M. , Kovar, A. , Lehr, T. , Milligan, P. , Nock, V. , Ramusovic, S. , Riggs, M. , Schaller, S. , Schlender, J. , Schmidt, S. , Sevestre, M. , Sjögren, E. , Solodenko, J. , Staab, A. and Teutonico, D. (2019), Open Systems Pharmacology Community—An Open Access, Open Source, Open Science Approach to Modeling and Simulation in Pharmaceutical Sciences. CPT Pharmacometrics Syst. Pharmacol, 2019, 8 (12): 878–882.  Available from: https://doi.org/10.1002/psp4.12473

 

 

Use of Exposure-Response Information in Pediatric Drug Development

Presented by Marc Gastonguay, Ph.D. at Accelerating Drug Development for Polyarticular Juvenile Idiopathic Arthritis (pJIA) on October 2, 2019. Event details on the FDA website.

Considerations and Future Directions for the Development of Open-Source, Public License, Pharmacometric Software

Presented by Marc Gastonguay, Ph.D. at ACCP Annual Meeting September 17, 2019.

Improving Methods for Analyzing Antimalarial Drug Efficacy Trials: Molecular Correction Based on Length-Polymorphic Markers msp-1, msp-2, and glurp

Presentation by Katherine Kay Ph.D at R/Medicine. Boston, MA. 14 September 2019.

 

Solving the Package Management Puzzle

Pastoor, Devin. Presentation at R/Pharma. Cambridge, MA. 22 Aug 2019.

Prediction of maternal-fetal exposures of CYP450-metabolized drugs using physiologic pharmacokinetic modeling implemented in R and mrgsolve

Gastonguay, Madeleine. Presentation at R/Pharma. Cambridge, MA. 23 Aug 2019.

Leveraging Multiple R Tools to Make Effective Pediatric Dosing Decisions

Fisher, Jeannine. Presentation at R/Pharma. Cambridge, MA. 22 Aug 2019.

Open-Source and Open-Science to Progress the Integration of Pharmacometrics and Systems Pharmacology

Riggs, Matthew. Presentation at ISoPNE iPSP event. Cambridge, MA. 26 Aug 2019.

Development of an open-source physiologically-based pharmacokinetic model to predict maternal-fetal exposures of CYP450-metabolized drugs

Gastonguay MS, Russell S, Freling R, Riggs M, Kay K, Utsey K, Elmokadem A.

Poster presented at 2019 American Society for Clinical Pharmacology & Therapeutics (ASCPT). Washington DC. 14 March 2019.

Poster presented at ISoP Regional QSP Day 2019. Princeton, NJ. 16 July 2019.

Torsten: Stan functions for pharmacometric applications. New functionality including within chain parallel computation.

Zhang Y,  Gillespie W. Poster presented at 2019 Population Approach Group in Europe (PAGE). Stockholm, Sweden. 13 June 2019. Abstract IV-29.

M-EASE-2: A Modelling and simulation study conducted to further characterize the efficacy of low-dose Empagliflozin as Adjunctive to inSulin thErapy (M-EASE) in Type 1 Diabetes Mellitus (T1DM)

Johnston C, Riggs MM, Marquard J, Soleymanlou N, Nock V, Liesenfeld, K. Poster presented at 2019 Population Approach Group in Europe (PAGE). Stockholm, Sweden. 13 June 2019. Abstract IV-66.

M-EASE-1: A Modelling and simulation study conducted to further characterize the efficacy of low-dose Empagliflozin as Adjunctive to inSulin thErapy (M-EASE) in Type 1 Diabetes Mellitus

Eudy-Byrne R, Elmokadem A, Riggs MM, Johnston C, Marquard J, Soleymanlou N, Nock V, Liesenfeld K. Poster presented at 2019 Population Approach Group in Europe (PAGE). Stockholm, Sweden. 13 June 2019. Abstract III-02.

The M-EASE Studies: A Modeling and simulation approach to further characterize the efficacy of low-dose Empagliflozin as Adjunctive to InSulin ThErapy in type 1 diabetes

Perkins BA, Soleymanlou N, Rosenstock J, Skyler JS, Laffel LM, Liesenfeld K, Neubacher D, Riggs MM, Johnston CK, Eudy-Byrne RJ, Elmokadem A, George JT, Marquard J, Nock V. Poster presented at American Diabetes Association (ADA) 79th Scientific Sessions 2019. San Francisco, CA. 7-11 June 2019. Abstract 1198-P.

Pharmacokinetics of trastuzumab emtansine (T-DM1) as a single agent or in combination with pertuzumab in HER2-positive breast cancer patients with recurrent or locally advanced metastatic breast cancer

Lu D, Li C, Riggs M, Polhamus D, French J, Agarwal P, Chen S-C, Vadhavkar S, Patre M, Strasak A, Quartino A, Jin JY, Girish S. Cancer Chemother Pharmacol [Internet]. 2019 May 17. doi: 10.1007/s00280-019-03852-z.

Systems Pharmacology: A day in the life

Riggs MM. Slides presented at AAPS Forum to Connect Predictive Modelers in Boston, MA. 6 May 2019.

Causa Nostra: the potentially legitimate business of drawing causal inferences from observational data

Rogers JA. CPT Pharmacometrics Syst Pharmacol [Internet]. 2019 Feb 14; Available from: http://dx.doi.org/10.1002/psp4.12395

Vedolizumab exposure levels and clinical outcomes in ulcerative colitis: determining the potential for dose optimisation

Osterman MT, Rosario M, Lasch K, Barocas M, Wilbur JD, Dirks NL, Gastonguay MR. Aliment Pharmacol Ther. 49(4):408–18. February 2019.

Pharmacometrics and systems pharmacology for metabolic bone diseases

Riggs MM, Cremers S. British Pharmacological Society. 85(6):1136–46. 28 January 2019. https://doi.org/10.1111/bcp.13881

Midazolam dose optimization in critically ill pediatric patients with acute respiratory failure: A population pharmacokinetic-pharmacogenomic study

Zuppa AF, Conrado DJ, Zane NR, Curley MAQ, Bradfield J, Hakonarson H, Gastonguay MS, Moorthy G, Prodell J, Gastonguay MR. Crit Care Med [Internet]. 21 Jan 2019. DOI: 10.1097/CCM.0000000000003638

When learn/confirm leads to expand/understand: The expanding role of quantitative systems pharmacology in the betterment of therapeutics development

Riggs MM. Clin Pharmacol Ther. 98:394. 18 December 2018. doi: 10.1002/cpt.1287

Causa Nostra: The potentially legitimate business of drawing causal inferences from observational data

Rogers JA. Presentation at 2018 American Conference on Pharmacometrics (ACoP9). San Diego, CA. 9 Oct 2018.

Multiscale physiology-based modeling of mineral bone disorder in patients with chronic kidney disease and secondary hyperparathyroidism on hemodialysis: application to etelcalcetide treatment effects on calcium homeostasis

Riggs MM. Poster presented at 2018 American Conference on Pharmacometrics (ACoP9). San Diego, CA. 9 Oct 2018. Abstract #T-078.

A latent variable disease progression model for Duchenne muscular dystrophy

Hajjar J. Poster presented at 2018 American Conference on Pharmacometrics (ACoP9). San Diego, CA. 9 Oct 2018. Abstract #T-011.

Evaluations of scale: lessons learned while developing and extending a mineral and bone health multiscale systems pharmacology model

Riggs MM. Presentation at 2018 American Conference on Pharmacometrics (ACoP9). San Diego, CA. 9 Oct 2018.

Multi-scale iPSP model of physiologically-based representations to describe bone mineral homeostasis and interrelated effects

Riggs MM. Presentation at 2018 American Conference on Pharmacometrics (ACoP9). San Diego, CA. 8 Oct 2018.

A physiologically-based pharmacokinetic model for Voriconazole explores differences in pharmacokinetics between adults and children

Elmokadem A. Poster presented at 2018 American Conference on Pharmacometrics (ACoP9). San Diego, CA. 9 Oct 2018. Abstract #M-003.

Population pharmacokinetic modeling of enzyme replacement therapy ATB200 and pharmacological chaperone AT2221 in adult patients with Pompe Disease and simulation to predict adolescent exposures

Hajjar J. Poster presented at 2018 Annual Meeting of the American College of Clinical Pharmacology. Bethesda, MD. 23 Sep 2018.

Open and transparent pharmacometrics publication process

Gastonguay MR, Riggs MM. Lightning talk presented at International Society of Pharmacometrics New England 2018. Cambridge, MA. 12 Sep 2018.

Evaluating the impact of estimated partition coefficients by different methods using a unified PBPK model

Elmokadem A. Lightning talk presented at International Society of Pharmacometrics New England 2018. Cambridge, MA. 12 Sep 2018.

Development of an open and general physiologically-based pharmacokinetic model to predict maternal-fetal exposures for drugs metabolized by CYP isoenzymes

Gastonguay MS. Presented at the R/Medicine 2018 Conference. New Haven, CT. 8 Sep 2018.

Bayesian inference with partial differential equations using Stan

Zhang Y, Gillespie WR, Minjie Zhu. Poster presented at StanCon. Helsinki, Finland. 30 Aug 2018.

A perspective on the state of pharmacometrics and systems pharmacology integration

Trame MN, Riggs MM, Biliouris K, Marathe D, Mettetal J, Post TM, Rizk ML, Visser SAG, Musante CJ.  CPT Pharmacometrics Syst Pharmacol. doi:10.1002/psp4.12313. 21 August 2018.

R as the core technology to support modeling and simulation in pharma research, development, and post approval activities

Gastonguay MR. Lightning Talk presented at the 1st annual R/Pharma conference. Boston, MA. 16 August 2018.

Assisting pharmacometric simulation with the use of Shiny

Kang J. Lightning Talk presented at the 1st annual R/Pharma conference. Boston, MA. 16 August 2018.

The use of R in the development of physiological model for healthy growth

Eudy-Byrne R. Lightning Talk presented at the 1st annual R/Pharma conference. Boston, MA. 15 August 2018.

Moving fast without breaking things: navigating the R ecosystem in an enterprise environment

Pastoor D. Invited Talk presented at the 1st annual R/Pharma conference. Boston, MA. 15 August 2018.

Torsten: Stan functions for pharmacometrics applications

Gillespie WR. Presented at Stan for Pharmacometrics. Paris, France. 24 July 2018.

A model of the effects of GI disease and diet on child body composition in order to improve outcomes in those suffering from malnutrition

Eudy-Byrne R. Presented at the 17th American Pediatrics Healthcare & Infectious Diseases Congress, Vancouver, Canada, 28 June 2018.

Real world evidence and model-informed drug development – an antidiabetic drug cardiovascular outcome case study

Meng Z, Rogers JA, Sidi J, Tang Q, Patel D, Gaudel-Dedieu N, and Delvart D. Presented at the Annual Meeting of the Population Approach Group in Europe (PAGE) Montreux, Switzerland, May 2018. Abstract I-76.

The pharmacokinetics and pharmacodynamics of buprenorphine in neonatal abstinence syndrome

Moore JN, Gastonguay MR, Ng CM, Adeniyi-Jones SC, Moody DE, Fang WB, Ehrlich ME, Kraft WK. Clin Pharmacol Ther. 103 (6) 1029-1037; June 2018

Polymorphisms in cytochrome P450 are associated with extensive efavirenz pharmacokinetics and CNS toxicities in an HIV cohort in Botswana

Vujkovic M, Bellamy SL, Zuppa AF, Gastonguay MR, Moorthy GS, Ratshaa B, Han X, Steenhoff AP, Mosepele M, Strom BL, Bisson GP, Aplenc R, Gross R. Pharmacogenomics J. doi: 10.1038/s41397-018-0028-2. Epub June 1, 2018.

A joint design for functional data with application to scheduling ultrasound scans

Park SY, Xiao L, Wilbur JD, Staicu A, Jumbe NL. Computational Statistics and Data Analysis. 122:101-114. June 2018

Population pharmacokinetic – pharmacodynamic analysis to characterize the effect of empagliflozin on renal glucose threshold in patients with type 1 diabetes mellitus

Mondick J, Riggs M, Kaspers S, Soleymanlou N, Marquard J, Nock V. J Clin Pharmacol. 58 (5): 640-649; May 2018

Bayesian data analysis using Stan/Torsten for pharmacometric applications

Gillespie WR. Presented at the Midwest Biopharmaceutical Statistics Workshop (MBSW), Indianapolis, IN, May 2018.

Corrigendum: Exposure-efficacy relationships for vedolizumab induction therapy in patients with ulcerative colitis or Crohn’s disease

Rosario M, French JL, Dirks NL, Sankoh S, Parikh A, Yang H, Danese S, Colombel JF, Smyth M, Sandborn WJ, Feagan BG, Reinisch W, Sands BE, Sans M, Fox I. J Crohns Colitis 12 (4): 510. 2018 Mar 28.

Pharmacokinetic & pharmacodynamic modeling and simulation of recombinant human arylsulfatase A in patients with metachromatic leukodystrophy: a preliminary evaluation

Troy S, Wasilewski M, Godfrey CJ. Poster presented at the 14th Annual WORLDSymposium. San Diego, CA. 5-9 February 2018.

Exposure–response analyses of trastuzumab emtansine in patients with HER2-positive advanced breast cancer previously treated with trastuzumab and a taxane

Li C, Wang B, Chen SC, Wada R, Lu D, Wang X, Polhamus D, French J, Vadhavkar S, Strasak A, Smitt M, Joshi A, Samant M, Quartino A, Jin J, Girish S. Cancer Chemotherapy and Pharmacology 80 (6): 1079–90. December 2017.

A model of fracture risk used to examine the link between bone mineral density and the impact of different therapeutic mechanisms on fracture outcomes in patients with osteoporosis

Eudy-Byrne RJ, Gillespie W, Riggs MM. Gastonguay MR. J Pharmacokinet Pharmacodyn (2017).  First online 28 Oct 2017. https://doi.org/10.1007/s10928-017-9551-z

Model-based clinical pharmacology profiling and exposure-response relationships of the efficacy and biomarker of lebrikizumab in patients with moderate-to-severe asthma

Zhu R, Zheng Y, Dirks NL, Vadhavkar S, Jin JY, Peng K, Holweg CTJ, Olsson J, Matthews JG, Putnam WS. Pulmonary Pharmacology & Therapeutics 46: 88–98. October 2017.

Modeling methods for analyzing tumor dynamic data from basket trials

Ocampo-Pelland AS, French JL.  Presented at the 8th American Conference on Pharmacometrics (ACoP), Fort Lauderdale, FL, October 2017.

Post-approval decision making supported by modeling and simulation based on a variety of data sources

Gastonguay MR. Presented at the 8th American Conference on Pharmacometrics (ACoP), Fort Lauderdale, FL, October 2017.

Gaining efficiency by combining analytical and numerical methods to solve ODEs: Implementation in Stan and application to Bayesian PK/PD modeling

Margossian C and Gillespie WR.  Presented at the 8th American Conference on Pharmacometrics (ACoP), Fort Lauderdale, FL, October 2017.

Points to consider when making inferences about covariates

Gastonguay MR. Presented at the 8th American Conference on Pharmacometrics (ACoP), Fort Lauderdale, FL, October 2017.

Theory, empiricism, and a vision for the continued growth of pharmacometrics

Gastonguay MR.  The International Society of Pharmacometrics Lewis B. Sheiner Award Lecture presented at the 8th American Conference on Pharmacometrics (ACoP), Fort Lauderdale, FL, October 15, 2017.

Population pharmacokinetics and exposure–response of trastuzumab emtansine in advanced breast cancer previously treated with ≥2 HER2-targeted regimens

Chen S-C, Quartino A, Polhamus D, Riggs M, French J, Wang X, Vadhavkar S, Smitt M, Hoersch S, Strasak A, Jin JY, Girish S, and Li C. Br J Clin Pharmacol, 2017 Jul 21.

Time-to-event analysis of polatuzumab vedotin-induced peripheral neuropathy to assist in the comparison of clinical dosing regimens

Lu D, Gillespie WR, Girish S, Agarwal P, Li C, Hirata J, Chu YW, Kagedal M, Leon L, Maiya V, Jin JY. CPT: Pharmacometrics & Systems Pharmacology 6 (6): 401–8. June 2017.

Quantitative disease progression model of α-1 proteinase inhibitor therapy on computed tomography lung density in patients with α-1 antitrypsin deficiency

Tortorici MA, Rogers JA, Vit O, Bexon M, Sandhaus R A, Burdon J, Chorostowska-Wynimko J, Thompson P, Stocks J, McElvaney NG, Chapman KR, and Edelman JM. Br J Clin Pharmacol, June 2017.  doi: 10.1111/bcp.13358.

Population pharmacokinetics of morphine in patients with nonalcoholic steatohepatitis (NASH) and healthy adults

Pierre V, Johnston C, Ferslew B, Brouwer K, Gonzalez D.  CPT: Pharmacometrics & Systems Pharmacology. 2017;6(5):331-339. doi:10.1002/psp4.12185.

A joint optimal design for functional data with application to scheduling ultrasound scans

Park SY, Xia L, Wilbur J, Staicu AM, Jumbe NL.  Paper presented at: Eastern North American Region (ENAR) Spring Meeting of the International Biometric Society, March 2017, Washington, DC.

Population PK modeling and target attainment simulations to support dosing of ceftaroline fosamil in pediatric patients with acute bacterial skin and skin structure infections and community-acquired bacterial pneumonia

Riccobene TA, Khariton T, Knebel W, Das S, Li J, Jandourek A, Carrothers TJ, Bradley JS.  The Journal of Clinical Pharmacology, March 2017; 57: 345–355. doi: 10.1002/jcph.809

Evaluating effectiveness of case-matching for exposure-response analysis

Wilbur JD, Gupta M, Passey C, Roy A.  Poster presented at Eastern North American Region (ENAR) Spring Meeting of the International Biometric Society, March 2017, Washington, DC; Abstract 57d.

Population pharmacokinetic and pharmacodynamic analysis of buprenorphine for the treatment of neonatal abstinence syndrome

Moore JN, Gastonguay M, Adeniyi-Jones S, Moodey DE, Kraft WK.  Poster presented at: American Society for Clinical Pharmacology and Therapeutics (ASCPT) Annual Meeting, March 2017, Washington, DC; Abstract PII-099.

Population pharmacokinetic modeling of intravenous asparaginase erwinia chrysanthemi: Impact of varied infusion rates on exposure

Zomorodi K, Dumas T, Berry S, Johnston C, and Eller M. 

Population pharmacokinetics (PK) and exposure-response (E-R) analysis of trastuzumab emtansine (T-DM1) in patients with HER2+ metastatic breast cancer (MBC) who have received at least two prior regimens of HER2-directed therapy

Chen SC, Quartino AL, Polhamus D, Riggs MM, French JL, Wang X, Vadhavkar S, Smitt M, Hoersch S, Strasak A, Chernyukhin N, Jin JY, Girish S, Li C.  Abstract in Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Cancer Res 2017;77(4 Suppl):Abstract P4-21-26.

Animal-to-human dose translation of obiltoxaximab for treatment of inhalational anthrax under the US FDA animal rule.

Nagy CF, Mondick J, Serbina N, Casey LS, Carpenter SE, French J, Guttendorf R.  Clinical And Translational Science, 2016 Dec; 10: 12–19.

Systems pharmacology model development to provide physiologically based interpretation and drug development decision support in osteoporosis and other bone mineral-related diseases

Riggs, M.  Presented at Pharmacology 2016, annual meeting of the British Pharmacological Society, London, December 2016.

Crenezumab exposure–response across AD endpoints supports a higher dose for phase 3

Polamus D, Rogers JA, Paul R, Kshirsagar S, Sahasranaman S, Jin JY, Quartino AL.  Presented at the 9th Annual Clinical Trials on Alzheimer’s Disease (CTAD), December 2016.

Extension of multi-scale systems pharmacology model to evaluate effect of vitamin D3 pharmacokinetics on bone health

Ocampo-Pelland AS, Gastonguay MR, Riggs MM.  Presented at the 7th American Conference on Pharmacometrics (ACoP), Bellevue, WA; October 2016.

Stan functions for Bayesian pharmacometric modeling

Margossian CC and Gillespie WR.  Presented at the 7th American Conference on Pharmacometrics (ACoP), Bellevue, WA; October 2016.

MBMA of combined individual and aggregate data: strategies and issues

Gillespie WR. Presented at the 7th American Conference on Pharmacometrics (ACoP), Bellevue, WA; October 2016.

Bayesian pharmacometric modeling with BUGS, NONMEM, and Stan

Gillespie WR.  Presented at the 7th American Conference on Pharmacometrics (ACoP), Bellevue, WA; October 2016.

Causal models with pharmacometric applications

French JL.  Presented at the 7th American Conference on Pharmacometrics (ACoP), Bellevue, WA; October 2016.

Efficacy projection of obiltoxaximab for treatment of inhalational anthrax across a range of disease severity

Yamamoto BJ, Shadiack AM, Carpenter S, Sanford D, Henning LN, O’Connor E, Gonzales N, Mondick J, French J, Stark GV, Fisher AC, Casey LS, Serbina NV. Antimicrob Agents Chemother 60:5787–5795. doi:10.1128/AAC.00972-16

Vedolizumab efficacy exposure–response relationship for ulcerative colitis patients (GEMINI I) based on causal inference analysis

Gastonguay MR, Lasch K, Barocas M, Rosario M, Wilbur JD, Dirks NL, Osterman MT.  Presented at the American College of Gastroenterology Annual Meeting, October, 2016.

Interactive simulation-based assessment of “go/no-go” decision making in Duchenne muscular dystrophy clinical trials

Hajjar J, French JL, Gastonguay MR.  Presented at the 7th American Conference on Pharmacometrics (ACoP), Bellevue, WA; October 2016.

Automation of Population Pharmacokinetic-Pharmacodynamic Modeling Reports Using the RShiny Application: TFL Generator

Melhem M, Polhamus D, Lau T, Chen P, Narayanan A, Clements JD, Gibbs J, Seegan G.  Presented at the 7th American Conference on Pharmacometrics (ACoP), Bellevue, WA; October 2016.

Pharmacokinetics (PK) and exposure-response (E-R) analysis of Kadcyla (K) as a single agent or in combination with Perjeta (P) in patients with human epidermal growth factor receptor 2 positive (HER2+) metastatic breast cancer (MBC) who have not received prior chemotherapy for their metastatic disease

Lu D, Li C, Polhamus D, French JL, Riggs MM, Agarwal P, Chen SC, Wang X, Smitt M, Patre M, Strasak A, ChernyukhinN , Quartino AL, Jin JY, Girish S.  Presented at the 7th American Conference on Pharmacometrics (ACoP), Bellevue, WA; October 2016.

Penetration of ceftaroline into the epithelial lining fluid of healthy adult subjects

Riccobene TA, Pushkin R, Jandourek A, Knebel W, Khariton T.  Antimicrob Agents Chemother. 2016 Sep 23;60(10):5849-57.

Prototype Stan functions for Bayesian pharmacometric modeling

Gillespie WR and Margossian CC.  Presented at Stan for Pharmacometrics Day, Paris 22 Sep 2016.

A mathematical model to quantify links between bone mineral density, patient factors and therapeutic interventions on fracture risk in patients with osteoporosis

Eudy-Byrne RJ, Gillespie WR, Riggs MM, Gastonguay MR.  Poster presented at: American Society for Bone and Mineral Research Annual Meeting; September 2016.

Population pharmacokinetics and exposure-response (efficacy and safety/tolerability) of empagliflozin in patients with type 2 diabetes

Baron KT, Macha S, Broedl UC, Nock V, Retlich S, Riggs M.  Diabetes Ther. 2016 Sep;7(3):455-71.

Facilitating clinical trial simulation in Alzheimer’s disease using the CAMD IPD, literature summary level data, and the ‘adsim’ R package

Polhamus D.  Presented at The Joint Statistical Meetings (JSM), August, 2016.

Optimal design for sampling functional data

Park SY, Xia L, Wilbur J, and Staicu, AM.  Presented at The Joint Statistical Meetings (JSM), August 2016, Chicago, IL; Abstract 319197.

Comparisons of multiple exposure-response methodologies in oncology.

Polhamus D, French J, Chen SC, Wang B, Li C, Lu D, Girish S, Jin J, Quartino A.  Presented at the Annual Meeting of the Population Approach Group in Europe (PAGE), Lisboa, June 2016.

Comparison of recursive partitioning analysis and receiver operating characteristic (ROC) analysis for patient identification

Chen SC, Riggs MM, Nueesch E, Strasak A, French J, Jin J, Girish S, Li C.  Presented at the Annual Meeting of the Population Approach Group in Europe (PAGE), Lisboa, June 2016.

A case study in comparing cognitive development across populations

French JL, Racine A, van Buuren S, Haggstrom J.  Presented at the Annual Meeting for the Population Approach Group in Europe (PAGE), Lisboa, June 2016.

Modeling Duchenne muscular dystrophy (DMD) disease progression as assessed by the 6-minute walk test.

Hajjar J, Fisher J, Gastonguay MR.  Presented at the Annual Meeting of the Population Approach Group in Europe (PAGE), Lisboa, June 2016.

Evaluating effectiveness of case-matching for exposure-response analysis

Wilbur JD, Gupta M, Passey C, Roy A.  Presented at the Annual Meeting of the Population Approach Group in Europe (PAGE), Lisboa, June 2016.

Zika microcephaly cutoffs revisited: A study of Non-parametric methods in fetal growth

Wilbur JD, Ohuma E, Xiao L, Mouksassi S, Hafen R.  Presented at the Annual Meeting of the Population Approach Group in Europe (PAGE), Lisboa, June 2016.

The role of simulation in assessing extrapolation assumptions

Gastonguay MR.  Presented at the Quantitative Assessment of Assumptions to Support Extrapolation of Efficacy in Pediatrics: FDA – U Maryland CERSI Cosponsored Workshop.  FDA. June 1, 2016.

Comparing the performance of four open-source methods for multiple parameter estimation in a systems pharmacology model

Eudy RJ, Riggs MM, Baron K.  Presented at the Sanofi–MSISB Mount Sinai Systems Pharmacology Symposium, June 2016.

Dexmedetomidine pharmacology in neonates and infants after open heart surgery

Su F, Gastonguay MR, Nicolson SC, DiLiberto M, Ocampo-Pelland A, Zuppa AF. Anesth Analg. 2016 May;122(5):1556-66.

Estimation of exposure-response relationships in the presence of confounding

French JL.  Presented at Trends and Innovation in Clinical Trial Statistics Conference, Durham, NC; May 2016.

Big Data: Challenges and opportunities for clinical pharmacology

Flockhart D, Bies RR, Gastonguay MR, Schwartz SL.  Br J Clin Pharmacol. 2016 May;81(5):804-6.

Model-based meta-analysis for development of a population-pharmacokinetic (PPK) model for Vitamin D3 and its 25OHD3 metabolite using both individual and arm-level data

Ocampo-Pelland AS, Gastonguay MR, French JF, Riggs MM.  J Pharmacokinet Pharmacodyn. 2016 Apr;43(2):191-206.

Mixed-effects modelling to quantify the effect of empagliflozin on renal glucose reabsorption in patients with type 2 diabetes

Mondick J, Riggs M, Sasaki T, Sarashina A, Broedl UC, Retlich S. Diabetes Obes Metab. 2016 Mar;18(3):241-8.

Dose-response and exposure-response modeling of alpha-1 proteinase inhibitor (A1-PI) in patients with A1-PI deficiency based on RAPID and RAPID extension trials

Rogers JA, Tortorici MA, Viti O, Brexon M, Sandhaus RA, Burdon J, Piitulainen E, Seersholm N, Stocks J, McElvaney NG, Chapman KR, Edelman JM.  Presented at the American Society for Clinical Pharmacology and Therapeutics (ASCPT) Annual Meeting, San Diego, CA, March 2016.

Systematic review and meta-analysis of serious infections with tofacitinib and biologic disease-modifying antirheumatic drug treatment in rheumatoid arthritis clinical trials

Strand V, Ahadieh S, French J, Geier J, Krishnaswami S, Menon S, Checchio T, Tensfeldt TG, Hoffman E, Riese R, Boy M, Gómez-Reino JJ.  Arthritis Res Ther. 2015 Dec 15;17:362.

Exposure-Response Modeling and Simulation to Support Evaluation of Efficacious and Safe Exposure and Dose Range for Asfotase Alfa in Patients With Hypophosphatasia

Pradhan RS, Gastonguay MR, Gao X, Monteleone JPR, Lathia CD, Fisher J, Godfrey C, Dirks NL, Melian A, Thompson DD.  Poster presented at ASBMR 2015 American Society for Bone and Mineral Research’s Annual Meeting. 9-12 October 2015.

Facilitating cardiovascular safety exposure-response modeling in early-phase clinical studies with the cardioModel package for R

Conrado DJ, Hather GJ, Chen D, Denney WS. Facilitating Cardiovascular Safety Exposure-Response Modeling in Early-Phase Clinical Studies with the cardioModel Package for R.  Presented at the 6th American Conference on Pharmacometrics (ACoP), Arlington, VA, October 2015

PK-PD analysis of PASI with data at boundary: BI 655066, an anti-IL-23A mAb for the treatment of psoriasis

Lalovic B, Rogers JA, French J, Flack M. PK-PD Analysis of PASI with Data at Boundary: BI 655066, an Anti-IL-23A mAb for the Treatment of Psoriasis.  Presented at the 6th American Conference on Pharmacometrics (ACoP), Arlington, VA, October 2015

A pharmacometrician’s perspective for utilization of big data

Gastonguay MR.  Presented at the 6th American Conference on Pharmacometrics (ACoP), Arlington, VA; October 2015.

A modeling and simulation framework for exposure-response analysis in oncology: comparison and considerations of multiple methodologies

Polhamus D, French J, Chen S-C, Wang B, Li C, Lu D, Girish S, Jin J, Quartino A.  Presented at the 6th American Conference on Pharmacometrics, Arlington, VA; October 2015.

Simulation from ODE-based population PK/PD and systems pharmacology models in R with mrgsolve

Baron KT and Gastonguay MR.  Presented at the 6th American Conference on Pharmacometrics (ACoP), Arlington, VA; October 2015.

Linking a mechanistic model of bone mineral density to a time-to-event model of fracture

Eudy RF, Gillespie WR, Riggs MM, Gastonguay MR.  Presented at the 6th American Conference on Pharmacometrics (ACoP), Arlington, VA; October 2015.

Trends in the application of pharmacometric modeling and simulation in the development of orphan drugs in the 21st century

Hajjar J, Fisher J, Gastonguay MR.  Presented at the 6th American Conference on Pharmacometrics (ACoP), Arlington, VA; October 2015.

Implementing FDA specifications in R for submission of analysis datasets

Bergsma T and Pivirotto S.  Presented at the 6th American Conference on Pharmacometrics (ACoP), Arlington, VA, October 2015.

Modeling & simulation: Filling the knowledge gap in rare diseases. Return on Investment on the Utilization of Systems Pharmacology and pharmacometrics in drug development for rare diseases: challenges and opportunities

Gastonguay MR and Godfrey CJ.  American College of Clinical Pharmacology (ACCP) Workshop, September 26, 2015.

A priori identifiability of target-mediated drug disposition models and approximations

Eudy RJ, Riggs MM, Gastonguay MR. AAPS J. 2015 Sep;17(5):1280-4.

Population pharmacokinetic modeling of guanfacine in pediatric patients

Knebel W, Corcoran M, Ermer J, Gastonguay MR.  Clinical Pharmacokinetics (2015) 54: 875. doi:10.1007/s40262-015-0245-7

Connecting the dots: Linking osteocyte activity and therapeutic modulation of sclerostin by extending a multiscale systems model

Eudy RJ, Gastonguay MR, Baron KT, and Riggs MM.  CPT: Pharmacometrics & Systems Pharmacology. 2015;4(9):527-536. doi:10.1002/psp4.12013.

Population pharmacokinetics-pharmacodynamics of vedolizumab in patients with ulcerative colitis and Crohn's disease

Rosario M, Dirks NL, Gastonguay MR, Fasanmade AA, Wyant T, Parikh A, Sandborn WJ, Feagan BG, Reinisch W, Fox I.  Aliment Pharmacol Ther. 2015 Jul;42(2):188-202.

Malabsorption blood test: Assessing fat absorption in patients with cystic fibrosis and pancreatic insufficiency

Mascarenhas MR, Mondick J, Barrett JS, Wilson M, Stallings VA, Schall JI.  The Journal of Clinical Pharmacology, 55: 854–865. doi:10.1002/jcph.484

Assessment of propensity score and Mahalanobis distance matching in the exposure-response setting

Polhamus D, French J.  Presented at the Annual Meeting of the Population Approach Group in Europe (PAGE), Hersonissos, Greece; June 2015.

Model-based meta-analysis for development of a population pharmacokinetic (PPK) model for vitamin D3 and its 25OHD3 metabolite

Ocampo-Pellend AS, Gastonguay, French JL, Riggs MM. Presented at the Annual Meeting of the Population Approach Group in Europe (PAGE), Hersonissos, Greece; June 2015.

Sclerostin-mediated osteocyte control in bone remodeling: Extension of a multiscale systems model to consider new therapies for osteoporosis

Eudy RJ, Gastonguay MR, Baron KT, Riggs MM.  Presented at the Annual Meeting of the Population Group in Europe (PAGE), Hersonnisos, Greece; June 2015.

Altered morphine glucuronide and bile acid disposition in patients with nonalcoholic steatohepatitis

Ferslew B, Johnston C, Tsakalozou E, Bridges A, Paine M, Jia W, Stewart P, Barritt A and Brouwer K. Clinical Pharmacology and Therapeutics, 97: 419–427. doi:10.1002/cpt.66

FDA advisory meeting clinical pharmacology review utilizes a quantitative systems pharmacology (QSP) model: A watershed moment?

Peterson MC and Riggs MM.  CPT: Pharmacometrics & Systems Pharmacology, 2015 Mar; 4(3).

Modeling and simulation of the exposure-response and dropout pattern of guanfacine extended-release in pediatric patients with ADHD

Knebel W, Rogers JA, Polhamus D, Ermer J, Gastonguay MR. Journal of Pharmacokinetics and Pharmacodynamics, Feb 2015, Volume 42, Issue 1, pp 45–65. doi:10.1007/s10928-014-9397-6

Pharmacokinetic-pharmacodynamic modeling of the effect of varenicline on nicotine craving in adult smokers

P. Ravva, M. R. Gastonguay, H. M. Faessel, T. C. Lee, and R. Niaura. Nicotine & Tobacco Research, Volume 17, Issue 1, 1 January 2015, Pages 106–113.

Methods for determining similarity of exposures between adult and pediatric patients and trial design considerations

Marc Gastonguay. Presented at CERSI Workshop on the Use of Exposure Matching and Exposure Response for Extrapolation of Efficacy in Pediatric Drug Development. January 22, 2015.

Population pharmacokinetics of ε-aminocaproic acid in adolescents undergoing posterior spinal fusion surgery

Stricker PA, Gastonguay MR, Singh D, Fiadjoe JE, Sussman EM, Pruitt EY, Goebel TK, and Zuppa AF.  BJA: British Journal of Anaesthesia, 114(4), 689–699. http://doi.org/10.1093/bja/aeu459

Predicted impact of various clinical practice strategies on cardiovascular risk for the treatment of hypertension: a clinical trial simulation study

Jin Y, Bies R, Gastonguay MR, Wang Y, Stockbridge N, Gobburu J, Madabushi R. J Pharmacokinet Pharmacodyn. 2014 Dec;41(6):693-704. doi: 10.1007/s10928-014-9394-9

Modeling and simulation for medical product development and evaluation: highlights from the FDA-C-Path-ISOP 2013 workshop

Romero K, Sinha V, Allerheiligen S, Danhof M, Pinheiro J, Kruhlak N, Wang Y, Wang SJ, Sauer JM, Marier JF, Corrigan B, Rogers J, Lambers Heerspink HJ, Gumbo T, Vis P, Watkins P, Morrison T, Gillespie W, Gordon MF, Stephenson D, Hanna D, Pfister M, Lalonde R, Colatsky T. Journal of Pharmacokinetics and Pharmacodynamics, 2014 Dec;41(6):545-52. doi: 10.1007/s10928-014-9390-0.

Exposure−response modelling for empagliflozin, a sodium glucose cotransporter 2 (SGLT2) inhibitor, in patients with type 2 diabetes

Riggs MM, Seman LJ, Staab A, MacGregor TR, Gillespie W, Gastonguay MR, Woerle HJ, Macha S.  Br J Clin Pharmacol. 2014 Dec;78(6):1407-18. doi: 10.1111/bcp.12453.

Population pharmacokinetics of brodalumab in healthy adults and adults with psoriasis from single and multiple dose studies

Endres CJ, Salinger DH, Köck K, Gastonguay MR, Martin D, Klekotka P, Nirula A, and Gibbs MA. The Journal of Clinical Pharmacology, 54(11): 1230–1238, November 2014. doi:10.1002/jcph.334.

Altered fasting and postprandial serum bile acids in patients with non-alcoholic steatohepatitis (NASH)

Ferslew BC, Johnston CK, Tsakalozou EF, Su MI, Xie GU, Jia WE, Brouwer KLR and Barritt AS. Presented at the American Association for the Study Of Liver Diseases Annual Meeting, Boston, MA, November 2014; Abstract 831.

Web-based software for real-time simulation-assisted trial design in Alzheimer’s disease

Polhamus DG, Kang J, Rogers JA, and Gastonguay MR. Presented at the 7th Annual Clinical Trials on Alzheimer’s Disease (CTAD), November 2014.

Establishing a priori identifiability of target mediated drug disposition models

Eudy RJ and Gastonguay MR. Presented at the 5th American Conference on Pharmacometrics (ACoP), Las Vegas, NV, October 2014.

Exposure-response modeling in oncology: technical challenges and proposed solutions

Jonathan French. Presented at the 5th American Conference on Pharmacometrics (ACoP), Las Vegas, NV, October 2014.

Population pharmacokinetic (PPK) modeling and simulation to support pediatric dose selection of ceftaroline fosamil (CPT-F) in children aged 28 days to 12 years

Khariton T, Riccobene T, Knebel W, O’Neal T, Ghahramani P. Presented at the 5th American Conference on Pharmacometrics (ACoP), Las Vegas, NV, October 2014.

Self-auditing data tables for R

Bergsma T and Pivirotto S.  Presented at the 5th American Conference on Pharmacometrics (ACoP), Las Vegas, NV, October 2014.

Population pharmacokinetic/pharmacodynamic modeling of guanfacine effects on QTc and heart rate in pediatric patients

W. Knebel, J. Ermer, J. Purkayastha, P. Martin, and M. R. Gastonguay.  The AAPS Journal. 2014;16(6):1237-1246. doi:10.1208/s12248-014-9645-0.

An integrated natural disease progression model of nine cognitive and biomarker endpoints in patients with Alzheimer’s Disease

Quartino A, Polhamus D, Rogers JA, and Jin J. Presented at the Population Approach Group Europe (PAGE), Alicante, 2014. Abstract 3187.

Elastic cloud computing in pharmacometrics: Usage data and strategies for efficient workflows

Knebel W, Gastonguay M, Polhamus D, Hane JT. Presented at the Annual Meeting of the Population Analysis Group in Europe (PAGE), Alicante, Spain; June 2014; Abstract I-55.

Research designs for proof-of-concept chronic pain clinical trials: IMMPACT recommendations

J. S. Gewandter, R. H. Dworkin, D. C. Turk, M. P. McDermott, R. Baron, M. R. Gastonguay, I. Gilron, N. P. Katz, C. Mehta, S. N. Raja, S. Senn, C. Taylor, P. Cowan, P. Desjardins, R. Dimitrova, R. Dionne, J. T. Farrar, D. J. Hewitt, S. Iyengar, G. W. Jay, E. Kalso, R. D. Kerns, R. Leff, M. Leong, K. L. Petersen, B. M. Ravina, C. Rauschkolb, A. S. C. Rice, M. C. Rowbotham, C. Sampaio, S. H. Sindrup, J. W. Stauffer, I. Steigerwald, J. Stewart, J. Tobias, R.-D. Treede, M. Wallace, and R. E. White.  Pain. 2014 Sep;155(9):1683-95. doi: 10.1016/j.pain.2014.05.025. Epub 2014 May 24.

PKPD modeling of predictors for adverse effects and overall survival in sunitinib-treated patients with GIST

Hansson EK, Ma G, Amantea MA, French J, Milligan PA, Friberg LE, and Karlsson MO. CPT: Pharmacometrics & Systems Pharmacology. 2013;2(12):e85-. doi:10.1038/psp.2013.62.

PKPD modeling of VEGF, sVEGFR-2, sVEGFR-3, and sKIT as predictors of tumor dynamics and overall survival following sunitinib treatment in GIST

Hansson EK, Amantea MA, Westwood P, Milligan PA, Houk BE, French J, Karlsson MO and Friberg LE. CPT: Pharmacometrics & Systems Pharmacology. 2013;2(11):e84-. doi:10.1038/psp.2013.61

Clinical dementia rating modeling and simulation: Joint progression of CDR and biomarkers in the ADNI cohort

Polhamus DG, Rogers JA, Gillespie WR, French J. Presented at the Alzheimer’s Association International Conference (AAIC),  2013.

Mathematical modeling of systemic and hepatic disposition of morphine and morphine glucuronides in nonalcoholic steatohepatitis to inform study design

Johnston CK, Ferslew BC, Barritt AS, Brouwer KL. Presented at the American Association of Pharmaceutical Scientists Annual Meeting, San Antonio, TX, November 2013.

Extensions of a multiscale systems pharmacology model of bone mineral balance and its regulation of bone health

Riggs MM. Presented at Sunrise Session: Integration of Systems Modeling in Clinical Development: Successes, Challenges, and Future Outlook at the American American Society for Clinical Pharmacology and Therapeutics Annual Meeting, 2013.

Systems pharmacology model development to provide physiologically-based interpretation and drug development decision support in osteoporosis and other bone-related diseases

Riggs M.  Presented at the Annual Meeting of the American Society for Clinical Pharmacology and Therapeutics, 2013.

Pharmacokinetic modeling of the relationship between sustained virological response and plasma concentrations of faldaprevir or bi-207127 in hcv gt1-infected patients in sound-c2

Olson S, Baron K, Riggs M, Bocher WO, Mensa FJ.  Journal of Hepatology, 58:S492–S493.

An evaluation of calcilytic effects on parathyroid hormone and bone mineral density response using a physiologically-based, multiscale systems pharmacology model

Kyle T. Baron, Matthew M. Riggs, Ryoko Sawamura, Takako Shimizu, Fumihiko Okada, Jin Zhou, Takahiro Shibayama, Mendel Jansen. Presented at the American Society of Bone and Mineral Research (ASBMR), October, 2013.

Population pharmacokinetics of empagliflozin, a sodium glucose cotransporter 2 inhibitor, in patients with type 2 diabetes

Riggs MM, Staab A, Seman L, MacGregor TR, Bergsma TT, Gastonguay MR, Macha S.  The Journal of Clinical Pharmacology. 2013 Oct;53(10):1028-38. doi:10.1002/jcph.147

Can methods based on existing models really aid decision making in non-small-cell lung cancer (NSCLC) trials?

Presented at the Annual Meeting of the Population Approach Group Europe (PAGE), Glasgow; June, 2013. Abstract A-06.

Population pharmacokinetics of epsilon-aminocaproic acid in infants undergoing craniofacial reconstruction surgery

Stricker PA, Zuppa AF, Fiadjoe JE, Maxwell LG, Sussman EM, Pruitt EY, Goebel. TK, Gastonguay MR, Taylor JA, Bartlett SP, Schreiner MS.  Br J Anaesth. 2013 May;110(5):788-99. doi: 10.1093/bja/aes507

Population pharmacokinetics of atorvastatin and its active metabolites in children and adolescents with heterozygous familial hypercholesterolemia: Selective use of informative prior distributions from adults

Knebel W, Gastonguay MR, Malhotra B, El-Tahtawy A, Jen F and Gandelman K.  J Clin Pharmacol. 2013 May; 53 (5): 505-16. doi: 10.1002/jcph.66.

A cloud-based cluster computing platform for pharmacometric applications

Bergsma T, Knebel W, Polhamus D, Hane JT, Gastonguay MR. Presented at the 4th American Conference on Pharmacometrics (ACoP), Ft. Lauderdale; May 2013.

Opportunities and challenges of MBMA in oncology

French J. Presented at the 4th American Conference on Pharmacometrics (ACoP), Ft. Lauderdale; May 2013.

A novel model-based meta-analysis to indirectly estimate the comparative efficacy of two medications: an example using DPP-4 inhibitors, sitagliptin and linagliptin, in treatment of type 2 diabetes mellitus

Gross JL, Rogers JA, Polhamus D, Gillespie W, Friedrich C, Gong Y, Monz BU, Patel A, Staab A, Retlich S. BMJ Open. 5 March 2013.

Facilitating pharmacometric workflow with the metrumrg package for R

Bergsma TT, Knebel W, Fisher J, Gillespie WR, Riggs MM, Gibiansky L, Gastonguay MR. Comput Methods Programs Biomed. 2013 Jan;109(1):77-85.

Predicting nonlinear changes in bone mineral density over time using a multiscale systems pharmacology model

Peterson MC and Riggs MM. CPT Pharmacometrics Syst Pharmacol. 2012 Nov; 1(11): e14. Published online 2012 Nov 14. doi: 10.1038/psp.2012.15

Integrated pharmacometrics and systems pharmacology model-based analyses to guide GnRH receptor modulator development for management of endometriosis

Riggs MM, Bennetts M, van der Graaf PH, and Martin SW.  CPT Pharmacometrics Syst Pharmacol. 2012 Oct; 1(10): e11. Published online 2012 Oct 17. doi: 10.1038/psp.2012.10

Novel model-based meta-analysis to estimate comparative efficacies of 2 drugs: An example using the DPP-4 inhibitors linagliptin and sitagliptin in type 2 diabetes mellitus

Gross JL, Rogers JA, Polhamus D, Gillespie W, Patel S, Friedrich C, Gong Y, Monz B, Staab A, Retlich S.  American Diabetes Association 72nd Scientific Sessions, 2012.

Population pharmacokinetic-pharmacodynamic analysis of istradefylline in patients with Parkinson disease

Knebel W, Rao N, Uchimura T, Mori A, Fisher J, Gastonguay MR, and Chaikin P. The Journal of Clinical Pharmacology, 2012; 52: 1468–1481. doi:10.1177/0091270011420566.

Combining patient-level and summary-level data for Alzheimer’s disease modeling and simulation: A beta regression meta-analysis

Rogers JA, Polhamus D, Gillespie WR, Ito K, Romero K, Qiu R, Stephenson D, Gastonguay MR, Corrigan B. J Pharmacokinet Pharmacodyn. October 2012, Volume 39, Issue 5, pp 479-498.

Qualification of a physiologically-based model for predicted bone marker and bone mineral density changes associated with denosumab treatment

Riggs MM, Baron KT, Plan EL, Gastonguay MR. Presented at American Society of Bone Mineral Research (ASBMR) Annual Meeting, Minneapolis, MN; October 14, 2012 (Abstract SU0363).

Modeling and simulation of guanfacine extended-release to support pediatric trial design

Knebel W, Rogers JA, Polhamus D, Youcha S, White C, Ermer J, and Gastonguay M. American Academy of Child and Adolescent Psychiatry, 59th Annual Meeting. 2012.

Avagacestat (BMS-708163) exposures and study discontinuations in patients with mild-to-moderate Alzheimer’s disease

Abu Tarif M, Kaplita S, Berman RM, Coric V, Baron K.  Presented at the Alzheimer’s Association International Conference (AAIC), Vancouver, BC, July 2012.

Model-based analysis to support strategic decision making: A case study from the development of a 5HT6 antagonist for the treatment of Alzheimer’s disease

Rogers J, Lockwood P, Polhamus D, Brault Y, Desmet A, Ito K, Romero K, Qiu R, Gillespie W, Corrigan B, Gastonguay M.  Presented at the Alzheimer’s Association International Conference (AAIC), Vancouver, BC, July 2012.

Sumo: An authenticating web application with an embedded R session

Bergsma TT and Smith MS. The R Journal; June 2012, Vol. 4 Issue 1, p60-63.

Misclassification and discordance of measured blood pressure from patient’s true blood pressure in current clinical practice: A clinical trial simulation case study

Jin Y, Bies R, Gastonguay MR, Stockbridge N, Gobburu J, Madabushi R.  J Pharmacokinet Pharmacodyn. 2012 Jun;39(3):283-94.

Bayesian joint modeling of bone mineral density and repeated time-to-fracture event for multiscale bone systems model extension

Plan EL, Baron KT, Gastonguay MR, French JL, Gillespie WR, and Riggs MM. Presented at the 21st Annual Meeting of the Population Approach Group Europe (PAGE), Venice, Italy, 2012, Abstract 2592.

From evidence synthesis to trial optimization: The adsim package for model-based simulation in Alzheimer’s disease

Polhamus D, Rogers JA, Gillespie W, French J, and Gastonguay M.  Presented at the 21st Annual Meeting of the Population Approach Group Europe (PAGE), Venice, Italy, June 2012, Abstract 2580.

Model-based meta-analysis comparison of the effects of linagliptin and sitagliptin on HbA1c levels in patients with type 2 diabetes mellitus

Rogers JA, Polhamus D, Gillespie W, Friedrich C, Staab A, and Retlich S. Presented at the 21st Annual Meeting of the Population Approach Group Europe (PAGE), Venice, Italy, June 2012, Abstract 2448.

Systematic extension of a physiologic model of bone and calcium homeostasis

Riggs MM. . Presented at the AAPS Biotechnology Conference, San Diego, CA; May 22, 2012.

Building a scalable pharmacometrics platform in the cloud

Hane J and Kraut A.  Presented at BioIT World Conference and Expo, Boston, MA; April 23-25, 2012.

Population pharmacokinetics and exposure-response of albinterferon alfa-2b

Riggs MM, Bergsma TT, Rogers JA, Gastonguay MR, Subramanian GM, Chen C, Devalaraja M, Corey AE, Sun H, Yu J, and Stein DS. The Journal of Clinical Pharmacology, 52: 475–486, April 2012. doi:10.1177/0091270011399576

The value of evidence synthesis: Model-based meta-analysis based on the CAMD database, the ADNI AD cohort data, and literature meta-data

Rogers JA, Polhamus D, Ito K, Qiu R, Gillespie W, Corrigan B. Presented at the 2012 American Society for Clinical Pharmacology and Therapeutics (ASCPT) Annual Meeting, National Harlbor, MD; March 2012.

Affiliation between the American Society of Pharmacometrics and the Journal of Pharmacokinetics and Pharmacodynamics.

D’Argenio DZ, Gastonguay MR, Brundage RC, Miller R, Tannenbaum SJ, Pfister M. J Pharmacokinet Pharmacodyn. 39(1):3. February 2012.

Two guys and a credit card: Metrum’s Amazon cloud makeover – A case study in transferring a life sciences IT infrastructure fully into the cloud

Davies K.  Bio-IT World, Feb 14, 2012.

Multiscale physiology-based modeling of mineral bone disorder in patients with impaired kidney function

Riggs MM, Peterson MC, Gastonguay MR. The Journal of Clinical Pharmacology. 52(1 Suppl):45S-53S. January 2012. doi:10.1177/0091270011412967

 

Applying a multiscale physiologic system model to evaluate bone-related disease and therapeutic responses

Riggs MM. Presented at First Indiana Clinical and Translational Sciences Institute (CTSI) Symposium on Disease and Therapeutic Response Modeling. Indiana University – Purdue University Indianapolis; Indianapolis, IN; 13 November 2011.

Application of modeling and simulation to support clinical drug development decisions in Alzheimer’s disease

Gastonguay MR.  Presented at First Indiana Clinical and Translational Sciences Institute (CTSI) Symposium on Disease and Therapeutic Response Modeling. Indiana University – Purdue University Indianapolis; Indianapolis, IN; 13 November 2011.

Attenuation of vancomycin pharmacodynamics (PD) due to dense inoculum methicillin-resistant Staphylococcus aureus (MRSA)

Johnston CK, Tsuji BT.  Presented at the American College of Clinical Pharmacy (ACCP) Annual Meeting; October 2011; Pittsburgh, PA.

Population pharmacokinetics of pentobarbital in neonates, infants, and children after open heart surgery

Zuppa AF, Nicolson SC, Barrett JS, Gastonguay MR.  J Pediatr. 159(3):414-419.e1-3. September 2011.

Full covariate models as an alternative to methods relying on statistical significance for inferences about covariate effects: A review of methodology and 42 case studies 

Gastonguay MR.  Presented at the 20th Annual Meeting of the Population Approach Group Europe (PAGE),  Athens, Greece,  June 2011. Abstract 2229.

Evaluation of rapid and sustained population viral response rates predicted under hepatitis C viral dynamic models

Baron KT, Ravva P, Purohit V, Riggs MM, Gastonguay MR. 6th International Workshop on Clinical Pharmacology of Hepatitis Therapy, June 2011.

Population pharmacokinetic/pharmacodynamic model of subcutaneous adipose 11β‐hydroxysteroid dehydrogenase type 1 (11β‐HSD1) activity after oral administration of AMG 221, a selective 11β‐HSD1 inhibitor

Gibbs JP, Emery MG, McCaffery I, Smith B, Gibbs MA, Akrami A, Rossi J, Paweletz K, Gastonguay MR, Bautista E, Wang M, Perfetti R, Daniels O.  J Clin Pharmacol. 51(6):830-41. June 2011.

Strategic data handling for pharmacometrics

Bergsma T. Presented at ACOP; April 2011; San Diego, CA.

A population pharmacokinetic model of tacrolimus in pediatric liver transplant recipients

Cirrincione-Dall G, Gastonguay MR, Knebel W, Bergsma T, Zhang AY, Patel D, Barrett JS, van Schaik R, Soldin OP, Soldin SJ, Nulmin I, Koren G, de Wildt SN. Presented at ACOP; April 2011; San Diego, CA.

A physiologically-based, multi-scale, mathematical model of integrated calcium homeostasis and bone remodeling

Riggs MM. Presented at ACOP; April 2011; San Diego, CA.

Systematic review of versioned files for modeling and simulation quality control: the“review” R package

Bergsma T, Fisher J, Gastonguay MR, Hane J, Knebel W, Riggs MM, Rogers JA. Presented at ACOP; April 2011; San Diego, CA.

A time to event approach for standard of care meta-analysis in HCV trials

Polhamus D, Baron KT, Purohit VS, Ravva P, Rogers JA, Gastonguay MR. Presented at ACOP; April 2011; San Diego, CA.

Evaluation of rapid and sustained population viral response rates predicted under hepatitis C viral dynamic models

Baron K, Ravva P, Purohit V, Riggs MM, Gastonguay MR. Presented at ACOP; April 2011; San Diego, CA.

Combining summary-level and patient-level data for longitudinal dose-response models: why and how

Rogers JA. Presented at ACOP; April 2011; San Diego, CA.

Application of a multiscale physiologically-based bone and calcium systems model to guide the development of GnRH receptor modulators for the management of endometriosis

Riggs MM, Bennetts M, Martin SW, Van Der Graaf PH. Presented at ACOP; April 2011; San Diego, CA.

Performance of Cpred/Cobs concentration ratios as a metric reflecting adherence to antidepressant drug therapy

Feng Y, Gastonguay MR, Pollock BG, Frank E, Kepple GH, Bies RR.  Neuropsychiatr Dis Treat. 7:117-25. 16 March 2011.

Population pharmacokinetic modeling of pantoprazole in pediatric patients from birth to 16 years

Knebel W, Tammara B, Udata C, Comer G, Gastonguay MR, Meng X.  J Clin Pharmacol. 51(3):333-45. March 2011.

A longitudinal dose-response model for the progression of alzheimers disease, based on a combination of summary-level and patient-level data

Rogers JA, Ito K, Gillespie WR, Corrigan BW, Gastonguay MR. Presented at the Fourth Annual Bayesian Biostatistics Conference, Houston, TX. 26–28 January 2011.

Quantifying uncertainty in predictions of hepatic clearance

Rogers JA, Wilbur J, Cole S, Bernhardt PW, Bupp JL, Lennon MJ, Langholz N, Steiner CP. Statistics in Biopharmaceutical Research. 3(4):515-525. (2011)

A physiologically-based, multiscale model used to predict progressive bone mineral density loss due to chronic renal disease

Riggs MM, Gastonguay MR, Peterson MC. Presented at 2010 American Association of Pharmaceutical Scientists (AAPS) Annual Meeting, New Orleans LA; 17 November 2010; Poster # W4403

Development of mechanistic/multiscale/systems biology models in clinical pharmacology and translational research: do the challenges outweigh the potential benefits?

Riggs MM.  2010 AAPS Clinical Pharmacology and Translational Research (CPTR) Open Forum; 16 November 2010.

Extension of a multiscale model of calcium homeostasis and bone remodeling to include the progressive effects of estrogen loss during menopause transition

Riggs MM, Gillespie WR, Gastonguay MR, Peterson MC. Presented at National Institute of General Medical Sciences Quantitative Systems Pharmacology Workshop II. Bethesda, MD; 9 September 2010.

Pharmacometrics as a discipline is entering the “industrialization” phase: standards, automation, knowledge sharing, and training are critical for future success

Romero K, Corrigan B, Tornoe CW, Gobburu JV, Danhof M, Gillespie WR, Gastonguay MR, Meibohm B, Derendorf H. J Clin Pharmacol. 50(9 Suppl):9S-19S. September 2010.

Defining the future of pharmacometrics: the American Society of Pharmacometrics

Pfister M, Brundage RC, Gastonguay MR, Miller R, Tannenbaum SJ, D’Argenio DZ. J Clin Pharmacol. ;50(9 Suppl):158S. September 2010.

ACoP: the tools, carpenters, and architects building the discipline of pharmacometrics

Brundage RC, Pfister M, D’Argenio DZ, Gastonguay MR, Miller R, Tannenbaum SJ. J Clin Pharmacol. 50(9 Suppl):7S-8S. September 2010.

Comparison of MCMC simulation results using NONMEM 7 or WinBUGS with BUGSModelLibrary

Gastonguay MR, Gillespie WR, Bauer RJ. Presented at PAGE 2010. Berlin, Germany. 8–11 June 2010

Utilizing NONMEM 7 and the intel fortran compiler in a distributed computing environment

Knebel W, Bergsma TT, Dagdigian C, Hane J, Gastonguay MR. Presented at PAGE 2010, 19th Meeting, Berlin, Germany, June 8–11, 2010.

Predicting nonlinear changes in BMD over time using a physiologically-based mathematical model

Peterson MC and Riggs MM. Presented at American Association of Pharmaceutical Scientists National Biotechnology Conference, Update on Quantitative Systems and Disease Models for Biologics. Mini–Symposium. San Francisco, CA; May 2010.

Population pharmacokinetics of dexmedetomidine in infants after open heart surgery

Su F, Nicolson SC, Gastonguay MR, Barrett JS, Adamson PC, Kang DS, Godinez RI, Zuppa AF. Anesth Analg. 110(5):1383-92. May 2010.

Multiscale modeling: the quantitative integration of systems biology, clinical pharmacology and translational research

Riggs MM. Presented at American Association of Pharmaceutical Scientists National Biotechnology Conference, Update on Quantitative Systems and Disease Models for Biologics. Mini–Symposium. San Francisco, CA; May 2010.

An issue in controlling the type 1 error rate with adaptive designs using time-to-event endpoints

Rogers JA. Presented at 3rd Annual FDA/MTLI Medical Device and IVD Statistics Workshop. 28 April 2010.

Comparative performance of bayesian markov chain monte carlo and maximum likelihood population estimation methods when applied to nonlinear pharmacokinetics of monoclonal antibodies

Dirks N, Gastonguay MR, Gillespie WR, Knebel W, Riggs MM, Panetta JC, and Meibohm B. Presented at ASCPT 111th Annual Meeting, March 17-20, 2010.

Exposure-response modeling and clinical trial simulation of the effect of tolterodine on QT intervals in healthy volunteers

Sweeney KR, Gastonguay MR, Benincosa L, Cronenberger CL, Glue P, Malhotra BK. Drug Discov Ther. 4(1):44-53. February 2010.

Quantitative assessment of exposure–response relationships for the efficacy and tolerability of varenicline for smoking cessation

Ravva JP, Gastonguay MR, French JL, Tensfeldt TG, and Faessel HM. Clinical Pharmacology & Therapeutics. 87(3):336-44. January 2010.

Population pharmacokinetics of intravenous ondansetron in oncology and surgical patients aged 1-48 months

Mondick JT, Johnson BM, Haberer LJ, Sale ME, Adamson PC, Coté CJ, Croop JM, Russo MW, Barrett JS, Hoke JF. Eur J Clin Pharmacol. 66(1):77-86. January 2010.

A physiologically based mathematical model of integrated calcium homeostasis and bone remodeling

Peterson MC, Riggs MM. Bone. 46: 49-63. January 2010.

The impact of missing data on model evaluation

Gastonguay MR. Presented at ACOP 2009. 6 October 2009; Mashantucket, CT.

Population dose-response model for ADAS-cog ccores in patients with alzheimers disease by meta-analysis of a mixture of summary and individual data

Gillespie WR, Rogers JA, Ito K, Gastonguay MR. Presented at ACOP 2009. October 4-7, 2009; Mashantucket, CT.

Prototype model library for bayesian pharmacokinetic/pharmacodynamic (PKPD) modeling in WinBUGS

Gillespie B, Gastonguay MR. Presented at ACOP 2009. October 4-7, 2009; Mashantucket, CT.

Clinical trial simulation to compare adaptive and fixed designs for a phase 3 clinical trial of Nacystelyn® (L-Lysine-N-acetyl-L-cysteinate) for cystic fibrosis

Rogers JA, Riggs MM, Coffiner M, Gillespie WR, Burford R, Vanderbist F, De Niet S, Gastonguay MR. ACOP 2009. October 4–7, 2009; Mashantucket, CT.

A systems biology model to describe long-term bone remodeling effects of estrogen in menopausal and postmenopausal women

Riggs MM, Peterson MC, Gastonguay MR. Presented at ACOP 2009. October 4-7, 2009; Mashantucket, CT.

Preliminary population pharmacokinetic modeling of PF-04360365, a humanized anti-amyloid monoclonal antibody, in patients with mild-to-moderate alzheimer’s disease

Nicholas T, Knebel W, Gastonguay MR, Bednar MM, Billing B, Landen JW, Kupiec JW, Corrigan B, Laurencot R, Zhao Q. Poster presented at the ICAD 2009 Annual Meeting; July 11–16, 2009; Vienna, Austria.

Population dose-response model for ADAS-cog scores in patients with alzheimer’s disease by meta-analysis of a mixture of summary and individual data

Gillespie B, Rogers JA, Ito K, Gastonguay MR. ASCPT 110th Annual Meeting, March 18-21, 2009; Washington D.C.

Population pharmacokinetic modeling of epoetin delta in pediatric patients with chronic kidney disease

Knebel W, Palmen M, Dowell JA, Gastonguay M. J Clin Pharmacol. 48(7):837-48. July 2008.

Population pharmacokinetic modeling of fosamprenavir in pediatric HIV-infected patients

Fisher J, Gastonguay MR, Knebel W, Gibiansky L, Wire MB. Poster presented at the American Conference on Pharmacometrics. March 9-12 2008; Tucson, Arizona.

Use of rpad, an open-source, interactive, web-based analysis program, for visualization during model-based drug development of adipiplon, a GABAA receptor partial agonist under investigation for the treatment of insomnia

Riggs MM, Bergsma TT, Gillespie WR, Gastonguay MR, Sprenger KJ. Poster presented at the American Conference on Pharmacometrics. March 9-12 2008; Tucson, Arizona.

Open source software tools for parallel computation of multiple MCMC chains with WinBUGS

Gillespie WR, Gastonguay MR, Knebel W, Georgalis G. Poster presented at the American Conference on Pharmacometrics. March 9-12 2008; Tucson, Arizona.

Facilitating the pharmacometrics work-flow with the mItools r package

Knebel W, Bergsma T, Fisher J, Georgalis G, Gibiansky L, Gillespie WR, Riggs MM, Gastonguay MR. Poster presented at the American Conference on Pharmacometrics. March 9-12 2008; Tucson, Arizona.

Bayesian approaches to mixed effects models for ordered categorical data

Gillespie WR, Gastonguay MR, Knebel W. Presented at the AAPS Annual Meeting; November 2007; San Diego, CA.

Population pharmacokinetic-pharmacodynamic modeling of istradefylline in patients with parkinson’s disease

Knebel W, Rao N, Bergsma T, Gastonguay M, Mori A, Uchimura T, Allenby K, Dvorchik B, Sussman N, Chaikin P. Presented at ACCP; October 14-17, 2007; Denver, CO.

Quantitative assessment of exposure-response relationships for the efficacy and tolerability of varenicline for smoking cessation

Rawa P, Faessel H, Gastonguay MR, Tensfeldt TG, Reeves K. Clin Pharmacol Ther. 81(S1) March 2007; Abstract PII-73: S72.

Population pharmacokinetic analysis of varenicline in adult smokers

Faessel HM, Rawa P, Gastonguay MR, Rohrbacher KD, Tenfeldt TG. Clin Pharmacol Ther; 81(S1). March 2007; Abstract PI-26: S20-21.

Exposure-response (PK-PD) applied to model-based drug development: A case study of drug x

Riggs M. FDA/Industry Statistics Workshop. 29 September 2006; Washington D.C.; Parallel Session 14: Case Studies in Modeling and Simulation, Abstract.

Development and evaluation of a population pharmacokinetic-pharmacodynamic model of darbepoetin alfa in patients with nonmyeloid malignancies undergoing multicycle chemotherapy

Agoram B, Heatherington AC, Gastonguay MR. AAPS Journal. 8(3), September 2006. doi: 10.1208/aapsj080364

Acknowledging and incorporating uncertainty in model-based inferences

Gastonguay MR, Gibiansky L. Presented at the ECPAG Conference. July 24-26, 2006; Rockville, MD; Workshop Poster Session, Abstract.

Acknowledging parameter uncertainty in the simulation-based design of an actinomycin-D pharmacokinetic study in pediatric patients with Wilms’ Tumor or rhabdomyosarcoma

Mondick JT, Gibiansky L, Gastonguay MR, Veal GJ, Barrett JS. Presented at PAGE 2006. June 14-16, 2006; Brugge/Bruges, Belgium; Abstract 938.

R/NONMEM Toolbox for simulation from posterior parameter (uncertainty) distributions

Gibiansky L and MR Gastonguay. Presented at PAGE 2006. June 14-16, 2006; Brugge/Bruges, Belgium; Abstract 958.

Model-based drug development: optimization of AQUAVAN® injection dosing for minimal-to-moderate sedation

Gibiansky E, Gibiansky L. Presented at PAGE 2006. June 14-16, 2006; Brugge/Bruges, Belgium; Abstract 959.

Acknowledging parameter uncertainty by simulating from posterior distributions with NONMEM and R

Gastonguay MR, Gibiansky L. Presented at the MUFPADA Annual Meeting. May 2-3, 2006; Ann Arbor, MI; Abstract.

Fit-for-Purpose Method Development and Validation for Successful Biomarker Measurement

A practical, iterative, “fit-for-purpose” approach to biomarker method development and validation is proposed, keeping in mind the intended use of the data and the attendant regulatory requirements associated with that use. Sample analysis within this context of fit-for-purpose method development and validation are well suited for successful biomarker implementation, allowing increased use of biomarkers in drug development.

NMQual: A tool to automate installation and facilitate qualification of NONMEM

Knebel B, Bergsma T, Gibiansky L, Hane JT, Gastonguay MR. Presented at PAGE Annual Meeting. June 16-17, 2005; Pamplona, Spain; Abstract 779.

Modeling and simulation guided design of a pediatric population pharmacokinetic trial for hydromorphone

Gastonguay MR, El-Tahtawy A. The AAPS Journal. 7(S2), June 2005. Abstract W5318.

Effect of NONMEM minimization status and number of replicates on bootstrap parameter distributions for population pharmacokinetic models: a case study

Gastonguay MR, El-Tahtawy A. Clinical Pharmacology and Therapeutics. 77(2), P2-P2; February 5, 2005.

Population pharmacokinetic model of sedative doses of GPI 15715 and propofol liberated from GPI15715

Gibiansky E, Gibiansky L, Enriquez J. Clinical Pharmacology and Therapeutics. 77(2), P48-P48; February 5, 2005.

Population pharmacokinetic–pharmacodynamic modeling of efaproxiral in cancer patients receiving radiation therapy

Gastonguay MR, Venitz J, Steffen R, Hackman J. Clinical Pharmacology and Therapeutics. 77(2), P89-P89, February 5, 2005.

NONMEM Non-influential correlated ETAs bug and how to fix it

Gibiansky L. Presented at AAPS Annual Meeting: PPDM Poster-Podium Session, November 10, 2004; Baltimore, MD.

The importance of the simulation expectation as a goodness of fit diagnostic for categorical population pharmacodynamic models

Gastonguay MR, Hane JT. The AAPS Journal. 6(S1) (2004); Abstract W4355.

A full model estimation approach for covariate effects: inference based on clinical importance and estimation precision

Gastonguay MR. The AAPS Journal. 6(S1) (2004); Abstract W4354.

Estimation and prediction of chaotic pharmacodynamic systems using nonlinear mixed-effects models: the butterfly effect

Gastonguay MR, Bies R. The AAPS Journal. 6(S1) (2004); Abstract W4353, 2004.