Status Toward the Implementation of Precision Dosing in Children

Abstract

Precision dosing is progressing beyond the conceptual and proof‐of‐concept stages toward implementation. As the availability of dosing algorithms, tools, and platforms increases, so do the investment in technology services and actual implementation of clinical services offering these solutions to patients. Nowhere is this needed more than in pediatric populations, which are still reliant on adult drug development and bridging strategies to support dosing, often in the absence of actual dose‐finding studies in the target pediatric population. Still, there is more work to be done to ensure that proper governance of these services is maintained, and that sustainability of these early implementations is guided by new science as it evolves and meaningful outcome data to confirm that such services deliver on both clinical and economic return on investment. In addition, the field should ensure that all approaches beyond a therapeutic drug monitoring–driven, pharmacokinetic‐centric approach should be considered as the tools and services evolve, especially when pediatric‐specific pharmacokinetic/pharmacodyamic and pharmacogenetic data are available and shown to be useful to guide dosing. This review evaluates current pediatric precision dosing efforts, highlighting their utility, longevity, and sustainability and assesses the current process for implementing such approaches examining current barriers that stand in the way of broader implementation and the stakeholders that must engage to ensure its ultimate success.

Model-Informed Estimation of Acutely Decreased Tacrolimus Clearance and Subsequent Dose Individualization in a Pediatric Renal Transplant Patient With Posterior Reversible Encephalopathy Syndrome

“…Similar precision dosing strategies have been used by our group to implement adaptive dosing control of other drugs, such as mycophenolic acid, sirolimus, and hydroxyurea, both during routine clinical care and prospective clinical trials. 31,36,[50][51][52][53]…”

Model‐Based Prediction of Irinotecan‐Induced Grade 4 Neutropenia in Advanced Cancer Patients: Influence of Demographic and Clinical Factors

“…We envision that the implementation of this model‐based approach in dose‐optimization studies of drugs with similar challenges as irinotecan will accelerate toward the vision of the FDA. Furthermore, integrating electronic health records 46 and machine‐learning applications 47 into this framework will facilitate model‐informed individualized dosing through advanced response and adaptation to dynamic patient physiology in a real‐world clinical setting.…”

Update on Therapeutic Drug Monitoring of Beta-Lactam Antibiotics in Critically Ill Patients—A Narrative Review

“…Standard β-lactams dosing in PICU settings has been associated with a 95% incidence of underdosing [ 125 ], which is an objective risk factor for antibiotics resistance [ 133 ] and/or reduced efficacy of treatment (morbidity and mortality risk). TDM approach in critically ill pediatric patients could be further upgraded with model-informed precision dosing (MIPD), where the dosing process (initial dose, time of infusion, timing, maintenance) is individualized by a specific commercial-based algorithm [ 134 ]. Algorithms that can be applied in pediatric patients include Auto Kinetics, Precise PK and BestDose [ 134 ].…”

“…TDM approach in critically ill pediatric patients could be further upgraded with model-informed precision dosing (MIPD), where the dosing process (initial dose, time of infusion, timing, maintenance) is individualized by a specific commercial-based algorithm [ 134 ]. Algorithms that can be applied in pediatric patients include Auto Kinetics, Precise PK and BestDose [ 134 ]. Beside algorithm-based antibiotic dosing, antibiotic stewardship programs and close cooperation with clinical pharmacists could optimize antibiotic management (dose, duration, type).…”