Model-Informed Precision Dosing

Model-Informed Precision Dosing (MIPD for short) is the use of pharmacometric models with computer software to optimize drug dosage for an individual patient.

Developed in the late 1960s under the impetus of clinical pharmacologists such as Lewis Sheiner and Roger Jelliffe, these approaches involve applying the equations and parameters describing a drug's pharmacokinetics and pharmacodynamics to define the best dosage regimen for a given individual, likely to produce circulating concentrations associated with maximum efficacy and minimum toxicity. Models typically take into account the patient's demographic characteristics (age, gender, ethnicity), clinical profile (body measurements, renal and hepatic function, comorbidities, co-medications, dietary habits, substances use) and possibly genetic factors (e.g. polymorphisms affecting cytochromes or drug transporters). When starting a treatment, these models can be used to select a priori the optimal dosage for a patient, based on simulations. During the treatment course, these same models can be used to integrate the results of Therapeutic Drug Monitoring (i.e. the measurement and medical interpretation of circulating drug concentrations) or the measurement of biomarkers of efficacy or toxicity, in an a posteriori approach to dose optimization, derived from Bayesian inference and feedback loops. Practically, these approaches make extensive use of computer software dedicated to the clinical use of pharmacokinetic/pharmacodynamic models, belonging to the computerized clinical decision support tools. They complement Model-Informed Drug Development (MIDD), which is mainly carried out by pharmaceutical industry researchers prior to marketing.

Prescribers are expected to make increasingly regular use of model-driven precision dosing tools for patient treatment and follow-up. Dosage individualization represents the quantitative aspect of precision medicine, while the qualitative aspect lies in the personalized choice of the best drug to treat a given pathology. This optimization of dose selection is especially desirable for drugs with narrow therapeutic index (i.e. effective concentration close to toxic ones). It is also important when a treatment is to be applied to patients with peculiarities, such as children, frail elderly persons, polymorbid patients or those already heavily treated. Technical hurdles still limit the wide implementation of these approaches in clinical practice, but it is to be expected that electronic patient records will pursue their development, thus enabling the increasing integration of model-informed precision dosing into medical practice.