Clinical Pharmacology Podcast with Nathan Teuscher

In this episode I discuss power calculations using the R package PowerTOST. I gave an introduction to power calculations and the statistical premise. I reviewed bioequivalence study designs that are commonly used for generic drug development, food effect evaluation, and drug-drug interaction studies. Links discussed in the show: PowerTOST R package PowerTOST instructions (scroll down to the Read Me information) Example R code (Change the filetype to .R after downloading) Statistical Power Statistical approaches to establishing Bioequivalence from FDA Calculation of CV You can connect with me on LinkedIn and send me a message Send me a message Sign up for my newsletter Copyright Teuscher Solutions LLC All Rights Reserved

In this episode I share a couple short clips from my conversation with Chad Briscoe and Greg Austin from BioTalk Unzipped (www.biotalkunzipped.com). We chat about a variety of topics including artificial intelligence and challenges with cell therapy development. You can hear the entire conversation on the BioTalk Unizipped podcast or YouTube channel in January. For now, enjoy these clips from the upcoming show! Links discussed in the show: BioTalk Unzipped main page BioTalk Unzipped YouTube channel You can connect with me on ⁠LinkedIn and send me a message⁠⁠ Send me a message⁠⁠ Sign up for my newsletter⁠

In this episode I discuss toxicokinetic analysis. This is the analysis of exposure data to support animal toxicology studies. I review the purpose of toxicology studies and how exposure metrics are used. Then I discuss different blood sampling schemes, and how to calculate exposure parameters for both full profiles and mean profiles. Links discussed in the show: You can connect with me on LinkedIn and send me a message Send me a message Sign up for my newsletter Copyright Teuscher Solutions LLC All Rights Reserved

This episode is a discussion of steady state pharmacokinetics. Steady state occurs when the amount of drug input is equivalent to the amount of drug elimination in a dosing interval. I discuss some key PK parameters at steady state and how to use them. I also discuss different methods of confirming that you have reached steady state. Links discussed in the show: You can connect with me on LinkedIn and send me a message Send me a message Sign up for my newsletter Copyright Teuscher Solutions LLC All Rights Reserved

In this episode I talk about dose proportionality, which is a surrogate for determining if we have linear clearance across a range of dose levels. I discuss 3 different methods that people use to determine dose proportionality along with a recommendation to use the power model method. Links discussed in the show: Power model method You can connect with me on ⁠LinkedIn and send me a message⁠⁠ Send me a message⁠⁠ Sign up for my newsletter⁠

This episode is a discussion of covariate search methods. I give definitions of covariates and predictors, and then I describe 3 different covariate search methods. For each method I describe the pros and cons associated with each one, including bias and time limitations. Links discussed in the show: Evaluation of the Boruta method for covariate selection You can connect with me on LinkedIn and send me a message Send me a message Sign up for my newsletter Copyright Teuscher Solutions LLC All Rights Reserved

In this episode I describe stimulatory indirect response PK-PD models. I describe how they work, how to set up the dataset for NONMEM, and how to code the model in NONMEM. This is the last of 4 episodes on different PK-PD models. Links discussed in the show: Indirect response PK-PD model equations Example NONMEM code for stimulatory indirect response PK-PD model You can connect with me on LinkedIn and send me a message Send me a message Sign up for my newsletter Copyright Teuscher Solutions LLC All Rights Reserved

In this episode I describe inhibitory indirect response PK-PD models. I describe how they work, how to set up the dataset for NONMEM, and how to code the model in NONMEM. This is the third of 4 episodes on different PK-PD models. Links discussed in the show: Indirect response PK-PD model equations Example NONMEM code for inhibitory indirect response PK-PD model You can connect with me on LinkedIn and send me a message Send me a message Sign up for my newsletter Copyright Teuscher Solutions LLC All Rights Reserved

In this episode I describe effect compartment PK-PD models. I describe how they work, a method of creating exploratory plots, how to set up the dataset for NONMEM, and how to code the model in NONMEM. This is the 2nd of 4 episodes on different PK-PD models. Links discussed in the show: Example NONMEM code for effect compartment model You can connect with me on LinkedIn and send me a message Send me a message Sign up for my newsletter Copyright Teuscher Solutions LLC All Rights Reserved

In this episode I describe direct effect PK-PD models. I describe how they work, a method of creating exploratory plots to identify direct effect models, how to set up the dataset for NONMEM, and how to code the model in NONMEM. This is the first of 4 episodes on different PK-PD models. Links discussed in the show: Example NONMEM code for direct effect model You can connect with me on LinkedIn and send me a message Send me a message Sign up for my newsletter Copyright Teuscher Solutions LLC All Rights Reserved

In this episode I discuss different methods of presenting pharmacokinetic and pharmacometrics results. I spoke about using PowerPoint and R Markdown derived HTML files. While I prefer HTML files in nearly all cases, I appreciate that sometimes PowerPoint format is required by some companies. I included multiple suggestions for both PowerPoint and HTML files that can help make the information presentation more effective. Links discussed in the show: Floating table of contents in R Markdown HTML output How to include CSS in your R Markdown Creating tabs in R Markdown Code folding in R Markdown You can connect with me on LinkedIn and send me a message Send me a message Sign up for my newsletter Copyright Teuscher Solutions LLC All Rights Reserved

This episode covers the terminal elimination rate constant calculated using non-compartmental analysis techniques. I reviewed how the rate constant is used to estimate half-life and extrapolate AUC to infinity, reviewed the methods for calculating the terminal rate constant value, and some important points about sample selection. Finally, I gave my reasons that we should ultimately stop talking about this and fretting over the method of calculation. Instead, let’s design better PK experiments with more optimal sampling to capture decline of the drugs we are studying. Links discussed in the show: You can connect with me on LinkedIn and send me a message Send me a message Sign up for my newsletter Copyright Teuscher Solutions LLC All Rights Reserved

This episode covered parallelization in modeling analyses. I spoke about across model parallelization and within model parallelization. I recommended some approaches for choosing how many cores to use in parallelization and also discussed different modeling computer systems you can use. Links discussed in the show: You can connect with me on LinkedIn and send me a message Send me a message Sign up for my newsletter Copyright Teuscher Solutions LLC All Rights Reserved

Today I covered 2 different topics. First, I spoke about residual error models when modeling. I discussed additive, proportional, and power models. I also reviewed combined models and when they can be helpful. Then I spoke about modeling report submission packages. I explained what I put in those packages, how they are used, and some potential changes coming in the future. Links discussed in the show: Publication on model master file You can connect with me on LinkedIn and send me a message Send me a message Sign up for my newsletter Copyright Teuscher Solutions LLC All Rights Reserved

This episode discusses simulations. I group simulations into 4 categories: (1) average response, (2) population, (3) individual, and (4) clinical trial simulations. I discuss details of each of these types of simulations and the different variability terms included in each one. I strongly recommend that we implement more clinical trial simulations in our work. This will help us design and execute more successful clinical trials that take advantage of our existing knowledge about a drug. Enjoy the show and connect with me using the links below if you have any questions. Links discussed in the show: You can connect with me on LinkedIn and send me a message Send me a message Sign up for my newsletter Copyright Teuscher Solutions LLC All Rights Reserved

Today’s show is about different work environments and not scientific topics. Throughout my career I have worked in many different types of companies, and I would like to share some observations with you from those experiences. I have held positions at startup companies or small biotechnology companies, large pharmaceutical companies, contract research laboratories, consulting firms, and working for myself as a consultant, and now as a software developer. Although my work has been focused on clinical pharmacology and pharmacometrics, the jobs and work environments are very different. Links discussed in the show: You can connect with me on LinkedIn and send me a message Send me a message Sign up for my newsletter Copyright Teuscher Solutions LLC All Rights Reserved

Today’s show discussed biosimilar development from a clinical pharmacology perspective. I describe what biosimilar products are and the necessary comparisons to the reference product. I review requirements for PK similarity, PD similarity, immunogenicity, and safety. I also touch on the idea of interchangeability between the biosimilar and reference products. Links discussed in the show: FDA Guidance on Clinical Pharmacology Data to support Biosimilarity (May 2016) FDA Guidance on Demonstrating Interchangeability (May 2019) FDA Q&A on Biosimilarity and Interchangeability (Sep 2023) You can connect with me on LinkedIn and send me a message Send me a message Sign up for my newsletter Copyright Teuscher Solutions LLC All Rights Reserved

Today’s show discussed approaches for modeling absorption profiles. I discussed the rationale behind modeling absorption and then described some common models. These included first-order absorption, zero-order absorption, transit compartments, distributed delay, Weibull, and zero/first order absorption. I also provided my recommendations on how to model absorption. Links discussed in the show: Distributed delay modeling in PK and PD Modeling biphasic formulation of methylphenidate You can connect with me on LinkedIn and send me a message Send me a message Sign up for my newsletter Copyright Teuscher Solutions LLC All Rights Reserved

Today’s show was an overview of Aplos Analytics and the development story for Aplos NCA. Please consider participating in the Early Access Program. Use the link below to learn more about Aplos NCA. Links discussed in the show: Aplos Analytics website Aplos Analytics Contact Us Page You can connect with me on LinkedIn and send me a message Send me a message Sign up for my newsletter Copyright Teuscher Solutions LLC All Rights Reserved

Today’s show is about hepatic impairment clinical studies. I cover the rationale behind evaluating hepatic impairment, common study designs, and key factors in the analysis and interpretation of the study results. I also share a huge announcement about Aplos NCA, a cloud-based solution for calculating NCA PK parameters. Use the link below to learn more about Aplos NCA. Links discussed in the show: FDA guidance EMA guideline Aplos Analytics website You can connect with me on LinkedIn and send me a message Send me a message Sign up for my newsletter Copyright Teuscher Solutions LLC