Purpose: We performed an economic evaluation, from a societal perspective, to examine the cost-utility and cost-effectiveness of a wearable multimodal seizure detection device: NightWatch. Methods:... Show morePurpose: We performed an economic evaluation, from a societal perspective, to examine the cost-utility and cost-effectiveness of a wearable multimodal seizure detection device: NightWatch. Methods: We collected data between November 2018 and June 2020 from the PROMISE trial (NCT03909984), including children aged 4-16 years with refractory epilepsy living at home. Caregivers completed questionnaires on stress, quality of life, health care consumption and productivity costs after two-month baseline and two-month intervention with NightWatch. We used costs, stress levels and quality-adjusted life years (QALYs) to calculate incremental cost-effectiveness ratios (ICERs). Missing items were handled by mean imputation. Sensitivity an-alyses were performed to examine the robustness of the results including bootstrap sampling. Results: We included 41 children (44% female; mean age 9.8 years, standard deviation (SD) 3.7 years). Total societal costs of the baseline period (T1) were on average euro 3,238 per patient, whereas after intervention (T2) this reduced to 2,463 (saving euro 775). The QALYs were similar between both periods (mean QALY 0.90 per participant, SD at T1 0.10, SD at T2 0.13). At a ceiling ratio of euro 50.000, NightWatch showed a 72% cost-effective probability. Univariate sensitivity analyses, on the perspective and imputation method, demonstrated result robustness. Conclusion: Our study suggests that NightWatch might be a cost-effective addition to current standard care for children with refractory epilepsy living at home. Further research with an additional target group for a large timeframe may support the findings of this research. Show less
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... 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. Show less
Background: Pediatric patients admitted for acute lung disease are treated and monitored in the hospital, after which full recovery is achieved at home. Many studies report in-hospital recovery,... Show moreBackground: Pediatric patients admitted for acute lung disease are treated and monitored in the hospital, after which full recovery is achieved at home. Many studies report in-hospital recovery, but little is known regarding the time to full recovery after hospital discharge. Technological innovations have led to increased interest in home-monitoring and digital biomarkers. The aim of this study was to describe at-home recovery of 3 common pediatric respiratory diseases using a questionnaire and wearable device. Methods: In this study, patients admitted due to pneumonia (n = 30), preschool wheezing (n = 30), and asthma exacerbation (AE; n = 11) were included. Patients were monitored with a smartwatch and a questionnaire during admission, with a 14-day recovery period and a 10-day "healthy" period. Median compliance was calculated, and a mixed-effects model was fitted for physical activity and heart rate (HR) to describe the recovery period, and the physical activity recovery trajectory was correlated to respiratory symptom scores. Results: Median compliance was 47% (interquartile range [IQR] 33-81%) during the entire study period, 68% (IQR 54-91%) during the recovery period, and 28% (IQR 0-74%) during the healthy period. Patients with pneumonia reached normal physical activity 12 days postdischarge, while subjects with wheezing and AE reached this level after 5 and 6 days, respectively. Estimated mean physical activity was closely correlated with the estimated mean symptom score. HR measured by the smartwatch showed a similar recovery trajectory for subjects with wheezing and asthma, but not for subjects with pneumonia. Conclusions: The digital biomarkers, physical activity, and HR obtained via smartwatch show promise for quantifying postdischarge recovery in a noninvasive manner, which can be useful in pediatric clinical trials and clinical care. Show less