Evidence-based drug treatment for special patient populations through model-based approaches

The majority of marketed drugs remain understudied in some patient populations such as pregnant women, paediatrics, the obese, the critically-ill, and the elderly. As a consequence, currently used dosing regimens may not assure optimal efficacy or minimal toxicity in these patients. Given the vulnerability of some subpopulations and the challenges and costs of performing clinical studies in these populations, cutting-edge approaches are needed to effectively develop evidence-based and individualized drug dosing regimens. Five key issues are presented that are essential to support and expedite the development of drug dosing regimens in these populations using model-based approaches: 1) model development combined with proper validation procedures to extract as much valid information from available study data as possible, with limited burden to patients and costs; 2) integration of existing data and the use of prior pharmacological and physiological knowledge in study design and data analysis, to further develop knowledge and avoid unnecessary or unrealistic (large) studies in vulnerable populations; 3) clinical proof-of-principle in a prospective evaluation of a developed drug dosing regimen, to confirm that a newly proposed regimen indeed results in the desired outcomes in terms of drug concentrations, efficacy, and/or safety; 4) pharmacodynamics studies in addition to pharmacokinetics studies for drugs for which a difference in disease progression and/or in exposure-response relation is anticipated compared to the reference population; 5) additional efforts to implement developed dosing regimens in clinical practice once drug pharmacokinetics and pharmacodynamics have been characterized in special patient populations. The latter remains an important bottleneck, but this is essential to truly realize evidence-based and individualized drug dosing for special patient populations. As all tools required for this purpose are available, we have the moral and societal obligation to make safe and effective pharmacotherapy available for these patients too.