TY - JOUR
T1 - How paediatric drug development and use could benefit from OMICs
T2 - A c4c expert group white paper
AU - Neumann, Eva
AU - Schreeck, Filippa
AU - Herberg, Jethro
AU - Jacqz Aigrain, Evelyne
AU - Maitland-van der Zee, Anke H.
AU - Pérez-Martínez, Antonio
AU - Hawcutt, Daniel B.
AU - Schaeffeler, Elke
AU - Rane, Anders
AU - de Wildt, Saskia N.
AU - Schwab, Matthias
N1 - Funding Information: The conect4children (c4c) project has received funding from the Innovative Medicines Initiative (IMI) 2 Joint Undertaking under grant agreement No 777389. The Joint Undertaking receives support from the European Union's Horizon 2020 research and innovation programme and EFPIA. E.N., E.S., F.S. and M.S. are supported by Robert Bosch Stiftung, Stuttgart, Germany. Funding Information: E.N., no conflicts of interest to declare. F.S., no conflicts of interest to declare. J.H., no conflicts of interest to declare. E.J.A., no conflicts of interest to declare. A.‐H.M.‐vanderZ. has received research grants outside the submitted work from GSK, Boehringer Íngelheim and Vertex, is the PI of a P4O2 (Precision Medicine for more Oxygen) public private partnership sponsored by Health Holland involving many private partners that contribute in cash and/or in kind (Boehringer Ingelheim, Breathomix, Fluidda, Ortec Logiqcare, Philips, Quantib‐U, Smartfish, SODAQ, Thirona, TopMD and Novartis), and has served in advisory boards for AstraZeneca, GSK and Boehringer Ingelheim with money paid to her institution. Antonio Pérez‐Martínez, no conflicts of interest to declare. D.H., no conflicts of interest to declare. E.S., no conflicts of interest to declare. A.R., no conflicts of interest to declare. S.deW. has received research grants outside the submitted work from Health Holland, in a public private partnership with UCB Pharma and served on advisory boards from AM Pharma, Novartis, Khondrion, and is also co‐chair of the IMI2 C4C strategic feasibility expert work package and director of the secretariat. M.S. has received research grants outside the submitted work from Green Cross WellBeing Co. Ltd, from Gilead Sciences Inc., from Agena Bioscience GmbH, CED Service GmbH, and from the Robert Bosch GmbH, and has received honoraria for oral presentations at academically organized congresses and meetings. Funding Information: The conect4children (c4c) project has received funding from the Innovative Medicines Initiative (IMI) 2 Joint Undertaking under grant agreement No 777389. The Joint Undertaking receives support from the European Union's Horizon 2020 research and innovation programme and EFPIA. E.N., E.S., F.S. and M.S. are supported by Robert Bosch Stiftung, Stuttgart, Germany. Publisher Copyright: © 2022 The Authors. British Journal of Clinical Pharmacology published by John Wiley & Sons Ltd on behalf of British Pharmacological Society.
PY - 2022/12
Y1 - 2022/12
N2 - The safety and efficacy of pharmacotherapy in children, particularly preterms, neonates and infants, is limited by a paucity of good-quality data from prospective clinical drug trials. A specific challenge is the establishment of valid biomarkers. OMICs technologies may support these efforts by complementary information about targeted and nontargeted molecules through systematic characterization and quantitation of biological samples. OMICs technologies comprise at least genomics, epigenomics, transcriptomics, proteomics, metabolomics and microbiomics in addition to the patient's phenotype. OMICs technologies are in part hypothesis-generating, allowing an in depth understanding of disease pathophysiology and pharmacological mechanisms. Application of OMICs technologies in paediatrics faces major challenges before routine adoption. First, developmental processes need to be considered, including a subdivision into specific age groups as developmental changes clearly impact OMICs data. Second, compared to the adult population, the number of patients is limited as are the type and amount of necessary biomaterial, especially in neonates and preterms. Thus, advanced trial designs and biostatistical methods, noninvasive biomarkers, innovative biobanking concepts including data and samples from healthy children, as well as analytical approaches (eg liquid biopsies) should be addressed to overcome these obstacles. The ultimate goal is to link OMICs technologies with innovative analysis tools, such as artificial intelligence at an early stage. The use of OMICs data based on a feasible approach will contribute to the identification complex phenotypes and subpopulations of patients to improve the development of medicines for children with potential economic advantages.
AB - The safety and efficacy of pharmacotherapy in children, particularly preterms, neonates and infants, is limited by a paucity of good-quality data from prospective clinical drug trials. A specific challenge is the establishment of valid biomarkers. OMICs technologies may support these efforts by complementary information about targeted and nontargeted molecules through systematic characterization and quantitation of biological samples. OMICs technologies comprise at least genomics, epigenomics, transcriptomics, proteomics, metabolomics and microbiomics in addition to the patient's phenotype. OMICs technologies are in part hypothesis-generating, allowing an in depth understanding of disease pathophysiology and pharmacological mechanisms. Application of OMICs technologies in paediatrics faces major challenges before routine adoption. First, developmental processes need to be considered, including a subdivision into specific age groups as developmental changes clearly impact OMICs data. Second, compared to the adult population, the number of patients is limited as are the type and amount of necessary biomaterial, especially in neonates and preterms. Thus, advanced trial designs and biostatistical methods, noninvasive biomarkers, innovative biobanking concepts including data and samples from healthy children, as well as analytical approaches (eg liquid biopsies) should be addressed to overcome these obstacles. The ultimate goal is to link OMICs technologies with innovative analysis tools, such as artificial intelligence at an early stage. The use of OMICs data based on a feasible approach will contribute to the identification complex phenotypes and subpopulations of patients to improve the development of medicines for children with potential economic advantages.
KW - OMICS technology
KW - clinical trials
KW - epigenomics
KW - paediatrics
KW - pharmacogenomics
UR - http://www.scopus.com/inward/record.url?scp=85124716721&partnerID=8YFLogxK
U2 - https://doi.org/10.1111/bcp.15216
DO - https://doi.org/10.1111/bcp.15216
M3 - Review article
C2 - 34997627
SN - 0306-5251
VL - 88
SP - 5017
EP - 5033
JO - British journal of clinical pharmacology
JF - British journal of clinical pharmacology
IS - 12
ER -