Publication: Clinical Pharmacology & Therapeutics
Modeling and simulation is proposed to support drug development phase transitions in oncology. Longitudinal tumor-size data recorded in patients are modeled to inform treatment efficacy, and the tumor growth inhibition (TGI) metrics are related to clinical end points, e.g., overall survival.
The mission of the International Society of Pharmacometrics (ISoP) Standards and Best Practices Committee is to provide best practices and recommendations for standard pharmacometric analyses—e.g., population pharmacokinetics/pharmacodynamics (PK/PD), exposure–response, disease models—with the goal of increasing consistency, productivity, quality, communication, and impact of pharmacometrics on decision making. We present the progress and plans of the committee … Continued
Fourteen drugs have been removed from the market worldwide because they cause torsade de pointes. Most drugs that cause torsade can be identified by assessing whether they block the human ether à gogo related gene (hERG) potassium channel and prolong the QT interval on the electrocardiogram. In response, regulatory agencies require new drugs to undergo … Continued
The motesanib phase III MONET1 study failed to show improvement in overall survival (OS) in non–small cell lung cancer, but a subpopulation of Asian patients had a favorable outcome. We performed exploratory modeling and simulations based on MONET1 data to support further development of motesanib in Asian patients. A model-based estimate of time to tumor … Continued
Model-based drug development in oncology is still lagging despite a good momentum in the clinical pharmacology and pharmacometry community in the past few years. The failure rate of late-stage oncology studies is one of the highest across therapeutic areas. The modeling of the relationship between longitudinal tumor size and overall survival has been proposed to … Continued
The pharmaceutical industry continues to face significant challenges. Very few compounds that enter development reach the marketplace, and the investment required for each success can surpass $1.8 billion. Despite attempts to improve efficiency and increase productivity, total investment continues to rise whereas the output of new medicines declines. With costs increasing exponentially through each development … Continued
Elevated cytokine levels are known to downregulate expression and suppress activity of cytochrome P450 enzymes (CYPs). Cytokine-modulating therapeutic proteins (TPs) used in the treatment of inflammation or infection could reverse suppression, manifesting as TP-drug-drug interactions (TP-DDIs). A physiologically based pharmacokinetic model was used to quantitatively predict the impact of interleukin-6 (IL-6) on sensitive CYP3A4 substrates. … Continued