Leiden University Scholarly Publications

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Kruizinga, M.D. (2022)

Trial@home for children: novel non-invasive methodology for the pediatric clinical trial of the future

Doctoral Thesis
Primary endpoints in pediatric clinical trials are currently very similar to those in adult trials1, and focus on quantifying or counting hard endpoints like mortality, hospital admissions and length of stay. Additionally, biochemical biomarkers in serum are often measured to assess drug effects on a biochemical level. The occurrence of mortality and hospital admissions is rare thanks to the improvements in clinical care that have occurred in the last century, and adopting these as primary endpoints in clinical trials gives disproportional weight to rare events which most patients will not experience. Conversely, length of stay for many clinical conditions is short, and this duration only captures a small part of the clinical recovery trajectory that patients must undergo. This dissertation described the development, technical validation and clinical validation of a new type of clinical endpoints ('value based endpoints') and a new clinical trial paradigm (The remote clinical...Show morePrimary endpoints in pediatric clinical trials are currently very similar to those in adult trials1, and focus on quantifying or counting hard endpoints like mortality, hospital admissions and length of stay. Additionally, biochemical biomarkers in serum are often measured to assess drug effects on a biochemical level. The occurrence of mortality and hospital admissions is rare thanks to the improvements in clinical care that have occurred in the last century, and adopting these as primary endpoints in clinical trials gives disproportional weight to rare events which most patients will not experience. Conversely, length of stay for many clinical conditions is short, and this duration only captures a small part of the clinical recovery trajectory that patients must undergo. This dissertation described the development, technical validation and clinical validation of a new type of clinical endpoints ('value based endpoints') and a new clinical trial paradigm (The remote clinical trial), consisting of digital endpoints and non-invasive pharmacokinetic sampling. Both have the potential to transform pediatric clinical trials and pediatric clinical care. The process towards implementation is challenging and can only proceed after a rigorous validation process. The current work provides a roadmap towards selection, validation, and implementation of digital endpoints, and describes preliminary steps taken for several candidates. The digital endpoints investigated in this work fulfill several validation criteria in a range of clinical conditions and, combined with non-invasive pharmacokinetics, may move the pediatric clinical trial completely towards the home. 
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Pediatrics
Wearable
Non-invasive
Pharmacokinetics
Smartwatch
Spirometry
Asthma
Saliva
Digital biomarker
All authors
Kruizinga, M.D.
Supervisor
Cohen, A.F.: Driessen, G.J.A.
Co-supervisor
Stuurman, F.E.
Committee
Dompeling, E.; Knibbe, C.A.J.; Boog, P.J.M.; Oijen, M.G.H. van
Qualification
Doctor (dr.)
Awarding Institution
Faculty of Medicine, Leiden University Medical Center (LUMC), Leiden University
Date
2022-02-10