Model-Informed Precision Dosing: Background, Requirements, Validation, Implementation, and Forward Trajectory of Individualizing Drug Therapy

Author:

Darwich Adam S.1,Polasek Thomas M.234,Aronson Jeffrey K.5,Ogungbenro Kayode6,Wright Daniel F.B.7,Achour Brahim6,Reny Jean-Luc89,Daali Youssef8,Eiermann Birgit10,Cook Jack11,Lesko Lawrence12,McLachlan Andrew J.13,Rostami-Hodjegan Amin46

Affiliation:

1. Logistics and Informatics in Health Care, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH), KTH Royal Institute of Technology, SE-141 57 Huddinge, Sweden

2. Department of Clinical Pharmacology, Royal Adelaide Hospital, Adelaide, South Australia 5000, Australia

3. Centre for Medicine Use and Safety, Monash University, Melbourne, Victoria 3052, Australia

4. Certara, Princeton, New Jersey 08540, USA

5. Centre for Evidence Based Medicine, Nuffield Department of Primary Care Health Sciences, University of Oxford, Oxford OX2 6GG, United Kingdom

6. Centre for Applied Pharmacokinetic Research, The University of Manchester, Manchester M13 9PT, United Kingdom;

7. School of Pharmacy, University of Otago, Dunedin 9054, New Zealand

8. Geneva Platelet Group, Faculty of Medicine, University of Geneva, CH-1211 Geneva, Switzerland

9. Division of General Internal Medicine, Geneva University Hospitals, CH-1211 Geneva, Switzerland

10. Inera AB, Swedish Association of Local Authorities and Regions, SE-118 93 Stockholm, Sweden

11. Drug Safety Research & Development, Pfizer Inc., Groton, Connecticut 06340, USA

12. Center for Pharmacometrics and Systems Pharmacology, University of Florida, Orlando, Florida 32827, USA

13. School of Pharmacy, The University of Sydney, Sydney, New South Wales 2006, Australia

Abstract

Model-informed precision dosing (MIPD) has become synonymous with modern approaches for individualizing drug therapy, in which the characteristics of each patient are considered as opposed to applying a one-size-fits-all alternative. This review provides a brief account of the current knowledge, practices, and opinions on MIPD while defining an achievable vision for MIPD in clinical care based on available evidence. We begin with a historical perspective on variability in dose requirements and then discuss technical aspects of MIPD, including the need for clinical decision support tools, practical validation, and implementation of MIPD in health care. We also discuss novel ways to characterize patient variability beyond the common perceptions of genetic control. Finally, we address current debates on MIPD from the perspectives of the new drug development, health economics, and drug regulations.

Publisher

Annual Reviews

Subject

Pharmacology,Toxicology

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