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PSI Pre-Clinical SIG Webinar: EC50 Estimation based on Multi-Donor Dose-Response Data

27 June 2023

Dr. Weiliang Qiu and Dr. Cheng Wenren

Dose–response relationships are important in assessing the efficacy and potency of drugs, which can usually be characterized by a 4-parameter logistic model: EC50, slope, lower asymptote, and upper asymptote. EC50, the concentration of a drug that induces a response halfway between the baseline and maximum, is a key quantity to evaluate drug potency. For multi-donor dose-response data, it is often the interest to estimate the overall EC50 and its 95% confidence interval. A few multi-donor EC50 estimation methods have been proposed in literature. Jiang and Kopp-Schneider (2014) systematically compared meta-analysis and nonlinear mixed-effects approaches and concluded that meta-analysis approach is simple and robust to summarize EC50 estimates from multiple experiments, especially suited in the case of small number of experiments, while nonlinear mixed-effects approach has issue of convergence failure probably due to overparameterization. In this talk, we investigated ways to improve nonlinear mixed-effects approach to alleviates its issue of convergence failure.

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