{"title":"Challenges, approaches and enablers: effectively triangulating towards dose selection in pediatric rare diseases.","authors":"Chandrasekar Durairaj, Indranil Bhattacharya","doi":"10.1007/s10928-023-09868-6","DOIUrl":null,"url":null,"abstract":"<p><p>Dose selection is an integral part of a molecule's journey to become medicine. On top of typical challenges faced in dose selection for more common diseases, pediatric rare disease has additional unique challenges due to the combination of 'rare' and 'pediatric' populations. Using the central theme of maximizing 'relevant' information to overcome information paucity, dose selection strategy in pediatric rare diseases is discussed using a triangulation concept involving challenges, approaches and very importantly, enablers. Using actual examples, unique scenarios are discussed where specific enablers allowed certain approaches to be used to overcome the challenges. The continued need for model-informed drug development is also discussed using examples of where modeling and simulation tools have been successfully used in bridging available information to select pediatric doses in rare disease. Additionally, challenges with translation and associated dose selection of new modalities such as gene therapy in rare diseases are examined with the lens of continuous learning and knowledge development that will enable pediatric dose selection of these modalities with confidence.</p>","PeriodicalId":16851,"journal":{"name":"Journal of Pharmacokinetics and Pharmacodynamics","volume":" ","pages":"445-459"},"PeriodicalIF":2.2000,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of Pharmacokinetics and Pharmacodynamics","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1007/s10928-023-09868-6","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2023/6/9 0:00:00","PubModel":"Epub","JCR":"Q3","JCRName":"PHARMACOLOGY & PHARMACY","Score":null,"Total":0}
引用次数: 0
Abstract
Dose selection is an integral part of a molecule's journey to become medicine. On top of typical challenges faced in dose selection for more common diseases, pediatric rare disease has additional unique challenges due to the combination of 'rare' and 'pediatric' populations. Using the central theme of maximizing 'relevant' information to overcome information paucity, dose selection strategy in pediatric rare diseases is discussed using a triangulation concept involving challenges, approaches and very importantly, enablers. Using actual examples, unique scenarios are discussed where specific enablers allowed certain approaches to be used to overcome the challenges. The continued need for model-informed drug development is also discussed using examples of where modeling and simulation tools have been successfully used in bridging available information to select pediatric doses in rare disease. Additionally, challenges with translation and associated dose selection of new modalities such as gene therapy in rare diseases are examined with the lens of continuous learning and knowledge development that will enable pediatric dose selection of these modalities with confidence.
期刊介绍:
Broadly speaking, the Journal of Pharmacokinetics and Pharmacodynamics covers the area of pharmacometrics. The journal is devoted to illustrating the importance of pharmacokinetics, pharmacodynamics, and pharmacometrics in drug development, clinical care, and the understanding of drug action. The journal publishes on a variety of topics related to pharmacometrics, including, but not limited to, clinical, experimental, and theoretical papers examining the kinetics of drug disposition and effects of drug action in humans, animals, in vitro, or in silico; modeling and simulation methodology, including optimal design; precision medicine; systems pharmacology; and mathematical pharmacology (including computational biology, bioengineering, and biophysics related to pharmacology, pharmacokinetics, orpharmacodynamics). Clinical papers that include population pharmacokinetic-pharmacodynamic relationships are welcome. The journal actively invites and promotes up-and-coming areas of pharmacometric research, such as real-world evidence, quality of life analyses, and artificial intelligence. The Journal of Pharmacokinetics and Pharmacodynamics is an official journal of the International Society of Pharmacometrics.