Clinical Pharmacology Podcast with Nathan Teuscher

Latest Episodes:

Model diagnostics and selection (Ep. 11) Oct 09, 2023

Show notes

This episode is a discussion on model evaluation and selection. I discussed diagnostic plots using predictions and residuals. I covered approaches for model selection and factors to consider. The focus of this episode is on models that predict continuous endpoints like drug concentration, biomarkers, or other continuous endpoints. Several figures are mentioned in the podcast and links to those images can be found below.

Links discussed in the show:

Figure 1: Observed vs Predicted for single-subject model (example of a good model fit). Figure generated using ggplot in R.
Figure 2: Observed vs Predicted for single-subject model (example of a poor model fit) using logarithmic scales. Figure generated using ggplot in R.
Figure 3: Observed vs Population and Individual Predicted for population model. Figures generated using ggCertara package in R.
Figure 4: Weighted residuals versus time, time after dose, and population prediction for population model. Figures generated using ggCertara package in R.
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Exposure-Response FDA Guidance (Ep. 10) Sep 25, 2023

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This episode is a discussion of the FDA guidance “Exposure-Response Relationships”. The relationship between drug exposure and response is critical to any determination of the safety and effectiveness of a drug product. In this episode I discuss the regulatory applications of exposure-response, the exposure-response relationships over time, the design of studies to collection exposure-response information, and modeling exposure-response relationships. Links discussed in the show: • FDA guidance “Exposure-Response Relationships” • ICH E4 guideline “Dose-Response Information” • 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

Finding a job in Clinical Pharmacology (Ep. 9) Sep 11, 2023

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This episode I talk about finding a job in Clinical Pharmacology or Pharmacometrics. I share a few thoughts from my experience followed by an interview with TJ Elder, the president of STEM Sourcing Recruiting and Staffing. TJ shares his insights and best practices on securing a new job in Clinical Pharmacology or Pharmacometrics.

Links discussed in the show:

• Connect with TJ Elder on LinkedIn

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QT Prolongation Guidance ICH E14 (Ep. 8) Aug 28, 2023

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This episode is a discussion of the FDA and ICH guidance E14 titled “Clinical Evaluation of QT/QTc Interval Prolongation and Proarrhythmic Potential for Non-Antiarrhythmic Drugs”. I start with background on the reason for these evaluations, then move to an overview of the key evaluations needed. I then discuss in some detail the thorough QT study and the concentration QT analysis. Then I provide some parting thoughts from my experiences with these analyses.

Links discussed in the show:

• ICH E14 Guidance (FDA website)

• Scientific white paper on concentration – QTc modeling by Garnett et. al

• Correction to publication

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Pediatric Extrapolation (Ep. 7) Aug 14, 2023

Show notes

Thank you to everyone who sent me feedback on this podcast. This episode is based on a suggestion from Kushal and Parmesh. In this episode, I discuss a general clinical pharmacology pediatric extrapolation plan. I describe the basics of the plan that is commonly proposed to regulatory bodies. I discuss specific technical approaches for extrapolation of adult pharmacokinetic data to pediatric patients and the extrapolation of adult exposure-response or pharmacodynamic data to pediatrics. And I conclude with a discussion of how to use physiologic-based pharmacokinetic models for pediatric extrapolation.

Links discussed in the show:

• Baby arms over head video

• PBPK Models in Pediatric Development

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Bioequivalence Guidances from FDA and EMA (Ep. 6) Jul 24, 2023

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Thank you to everyone who sent me feedback on this podcast. This episode is based on a suggestion from Drew. In this episode, I discuss bioequivalence studies and generic drug development. I will refer to guidance documents from both the European Medicines Agency or EMA and the US Food and Drug Administration or FDA. First, I will start with a discussion of the definition of bioequivalence or BE. Then I will discuss the statistical basis for bioequivalence and how you can leverage that for study design. And I will end with some unique challenges related to bioequivalence. Throughout, I will give practical suggestions based on my experiences in the past with BE studies.

Links discussed in the show:

• EMA guidance on bioequivalence

• FDA guidance on statistical approaches to bioequivalence (December 2022)

• FDA statistical approaches to BE (January 2001)

• FDA guidance on BE studies (2022)

• FDA product-specific guidances on BE

• Lecture from Helmut Schütz on finding intra-subject variability (or CV%) for power calculations

• PowerTOST R Package

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Nuances of NCA (Ep. 5) Jul 10, 2023

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In this episode, I discuss some nuances of non-compartmental analysis or NCA. I am going to focus on three separate parameters: Cmax, AUC, and the terminal elimination rate constant. These three are the most commonly used parameters to describe drug exposure. I’ll discuss the basic methodology for each and then discuss challenges that may arise when you are performing an analysis. Links discussed in the show: Images mentioned in the podcast Derivation of logarithmic AUC Calculating the elimination rate constant 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

Population PK FDA guidance (Ep. 4) Jul 03, 2023

Show notes

In this episode, I discuss the 2022 FDA Guidance on Population PK analysis. This includes a discussion of the applications, methods, and submission requirements for population PK models.

Links discussed in the show:

• FDA Population PK Guidance

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Comparing NCA and PK models (Ep. 3) Jul 03, 2023

Show notes

In this episode, I discuss two data analysis techniques: (1) non-compartmental analysis or NCA, and (2) PK modeling. I discuss the basic premise of each method and similarities and differences between them.

Links discussed in the show:

Publication about NCA by Johan Gabrielsson and Dan Weiner
Publication about PK modeling by Hartmut Derendorf et. al.
Play Angry Birds as a fun diversion today
Here’s a link to the Dexcom glucose sensor and the Tandem T-slim insulin pump
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Food Effect FDA Guidance (Ep 2) Jul 03, 2023

Show notes

In this episode, I discuss the 2022 FDA guidance on food effect studies. I discuss the timing of these studies in your development programs, various aspects of study design, and some unique exceptions to the standard food effect study.

Links discussed in the show:

• Here’s the current FDA guidance for food effect studies

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