On 10 February 2022, Matthijs Kruizinga successfully defended his PhD thesis titled ‘Trial@home for children - Novel non-invasive methodology for the pediatric clinical trial of the future’ at Leiden University, earning the distinction cum laude!
Primary endpoints in paediatric clinical trials are currently very similar to those in adult trials, 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. However, these hard endpoints have limitations, such as low occurrence of mortality and hospital admissions thanks to improvements in clinical care, and not taking into account the recovery trajectory patients must undergo after being discharged. Besides hard endpoints, clinic-based assessments and composite scores that are related to one or multiple components of the disease are often used as outcome, and although such scores are useful, these too have their limitations.
A shift from hard endpoints towards value-based endpoints is a natural progression of the current clinical trial paradigm. Value-based endpoints represent outcomes that patients care about, that are suitable to detect individual outcomes and that are measured frequently in a patients’ natural environment. These new objective biomarkers should be able to quantify if a drug or health care intervention helps individual patients, as opposed to that the drug works on a biochemical or organ system level. Implementing more value-based endpoints in clinical trials will likely improve the insights obtained from all trials, but the concept is especially relevant for the paediatric clinical trial. Trials in paediatric populations are difficult to conduct due to several reasons, such as a high proportion of non-consent, resulting in low recruitment rates. Many reasons for non-participation in a study are unavoidable, such as concerns about a study drug, randomization, or blinding. However, many of the current other barriers and limitations, such as burdensome study logistics and inconvenience for the child or the parents, could be surmounted by adopting a remote clinical trial paradigm.
The remote paediatric clinical trial paradigm, consisting of digital endpoints and non-invasive pharmacokinetic sampling, has the potential to transform paediatric clinical trials and paediatric clinical care. The process towards implementation is challenging and can only proceed after a rigorous validation process. Matthijs' thesis 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 fulfil several validation criteria in a range of clinical conditions and, combined with non-invasive pharmacokinetics, may move the paediatric clinical trial completely towards the home. Read his thesis here.
Matthijs was supervised by promotors prof. dr. A.F. Cohen and Prof. dr. G.J.A. Driessen and co-promotor Dr. F.E. Stuurman.
