Mathematical Optimization of Combination Drug Regimens

Mahya Aghaee, Helen Moore

When developing a new therapy or optimizing the dose of an established therapy, preclinical and clinical testing can provide a dose-response relationship that is used to determine the dose. However, when multiple therapies are being combined, it is challenging to test enough different combinations to find a regimen that gives the best results. Mathematical modeling can help in this and other settings. We start with a mechanistic model of a disease that incorporates therapeutic effects. This model can be validated with data. Then we apply constrained optimization methods to the model and predict a regimen that maximizes efficacy while simultaneously minimizing toxicity. The final validation is to test this predicted optimal regimen against others that are being considered. We use these techniques in a variety of disease and therapy settings to achieve better patient outcomes while also saving time and resources.



Aghaee M, Ledzewicz U, Robbins M, Bezman N, Cho HJ, Moore H. Determining Optimal Combination Regimens for Patients with Multiple Myeloma. 2022 Nov 17,

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Weiqing Gu and Helen Moore (2006) Optimal therapy regimens for treatment-resistant mutations of HIV. Contemporary Mathematics, Vol. 410, 139-152,