The THY-MOD Study - Personalized Dosing in Children with Hyper- or Hypothyroidism Computed by Mathematical Modeling

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Thyroid hormones are essential for normal brain development in the foetus and the infant, and for normal cognitive functions, normal growth and puberty in children and adolescents. Treatment of thyroid diseases (congenital and acquired hyper- or hypothyroidism) is difficult in infants and children. First, a carefully selected initial dose based on clinical experience is necessary. Second, after reaching a physiological balance of thyroid hormones, a continuous adjustment of the individual dose depending on age and thyroid function during adolescence and puberty is required to maintain euthyroidism. To mitigate the risk of negative neurological and developmental outcome such as cognitive impairment, it is essential to establish an optimal, personalized dosing that is continuously fine-tuned in neonates, infants and children with hypo- or hyperthyroidism. Dynamical mathematical models based on population pharmacokinetic / pharmacodynamic (PKPD) principles with individual covariate effects and model predictive control algorithms from optimal control theory will be developed and applied to retrospective longitudinal disease measurements from different hospitals. Developed models and algorithms will be validated based on prospective collected data during the duration of this project. This will allow the prediction of an optimal personalized dosing strategy that maintains thyroid hormones in an appropriate reference range. In general, models and algorithms to compute optimal personalized dosing in infants and children are a medical necessity to optimize long-term neurological outcome and consequently enhance performance in school and professional education, and to increase life quality of paediatric patients and their parents. Developed optimal control algorithms will be made freely available for educational purposes and for possible application to other disease areas.