LOGOS Theory: A Novel Framework for Dosage Regimen Design and Evaluation in Pharmacotherapy

Optimizing pharmacotherapy requires decisions beyond dosage itself but also the timing, duration and discontinuation of the treatment. This study introduces LOGOS (Longitudinal Optimization of Global Outcomes and Strategies) as a new, transparent, and reproducible mathematical framework for assessing and improving drug strategies. LOGOS aims twofold: a) to quantify the additional therapeutic benefit of different dosing strategies in the presence of common limitations in efficacy, resources and safety, and b) to find the best dosing strategies for the given pharmacokinetic/pharmacodynamic setting and its mathematical optimization. LOGOS assesses the safety at the time of treatment and after discontinuation in the absence of long-term drug toxicity. Mathematical analysis shows that the loading-maintenance-drug-free strategy is globally optimal for long treatment horizons whereas the first dose and then drug-free interval is the optimal strategy for shorter treatment horizons. Additional analyses have revealed mechanistic conditions for continuous or intermittent treatment. LOGOS could allow making better decisions in terms of dose adjustments, treatment intervals, planned interruptions, and safe restarting of treatment. The open-source Python implementation independently verified calculations and reproducibility procedures. LOGOS provides a general basis for an individualized and evidence-based treatment plan in the clinic.