Abstract
In a standard situation, a quantitative systems pharmacology model describes a “reference patient,” and the model parameters are fixed values allowing only the mean values to be described. However, the results of clinical trials include a description of variability in patients’ responses to a drug, which is typically expressed in terms of conventional statistical parameters, such as standard deviations (SDs) from mean values. Therefore, in this study, we propose and compare four different approaches: (1) Monte Carlo Markov Chain (MCMC); (2) model fitting to Monte Carlo sample; (3) population of clones; (4) stochastically bounded selection to generate virtual patient populations based on experimentally measured mean data and SDs. We applied these approaches to generate virtual patient populations in the QSP model of erythropoiesis. According to the results of our research, stochastically bounded selection showed slightly better results than the other three methods as it allowed the description of any number of patients from clinical trials and could be applied in the case of complex models with a large number of variable parameters.
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Notes
The Human normal erythropoiesys stimulated by ESA model is available at https://shiny.insysbio.com/ery/#!/. Prepared by Evgeny Metelkin, Alexander Stepanov (2019)
Data taken from Fig. 7
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We are grateful to the two anonymous reviewers for their insightful comments and suggestions which allowed us to significantly improve the results presentation.
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GK: created methodology and performed all data analysis; OD and GK: discussed and analyzed the results; AS and GL: created model of erythropoiesis. All authors drew the main conclusions and wrote the manuscript.
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Kolesova, G., Stepanov, A., Lebedeva, G. et al. Application of different approaches to generate virtual patient populations for the quantitative systems pharmacology model of erythropoiesis. J Pharmacokinet Pharmacodyn 49, 511–524 (2022). https://doi.org/10.1007/s10928-022-09814-y
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DOI: https://doi.org/10.1007/s10928-022-09814-y