Beyond snapshot dosing: a dynamic living digital twin framework for model-informed precision dosing in critical...

Model-Informed Precision Dosing (MIPD) has improved individualized therapy, but in critical illness its reliance on intermittently updated data creates a temporal mismatch between pharmacokinetic (PK) models and rapidly evolving physiology.

Synthesizing population pharmacokinetic (popPK) and data science literature, we examine the limitations of snapshot-based dosing, using vancomycin as example. We propose the Dynamic Living Digital Twin (DLDT) framework, which integrates high-frequency electronic health record data into adaptive state-space models such as Kalman filtering. Rather than adding more covariates, the DLDT reframes patient physiology as a continuously evolving latent state that can be updated using temporally dense clinical data. Methodological, infrastructural, and regulatory Software as Medical Device (SaMD) barriers are also evaluated. A non-systematic PubMed search identified relevant publications available up to March 2026.

The next advance in precision dosing will come from temporally adaptive PK reasoning. In this paradigm, patient physiology is treated as an evolving latent state, and clinical pharmacists may increasingly interpret exposure trajectories rather than isolated dose recommendations. Although technically feasible, implementation remains constrained by data interoperability and workflow integration challenges. Clinical pharmacists may therefore increasingly act as stewards of dynamic model outputs, using anticipated exposure trajectories to preempt PK shifts.