Objective Home-Monitoring of Physical Activity, Cardiovascular Parameters, and Sleep in Pediatric Obesity

Introduction: Clinical research and treatment of childhood obesity is challenging, and objective biomarkers obtained in a home-setting are needed. The aim of this study was to determine the potential of novel digital endpoints gathered by a home-monitoring platform in pediatric obesity. Methods: In this prospective observational study, 28 children with obesity aged 6–16 years were included and monitored for 28 days. Patients wore a smartwatch, which measured physical activity (PA), heart rate (HR), and sleep. Furthermore, daily blood pressure (BP) measurements were performed. Data from 128 healthy children were utilized for comparison. Differences between patients and controls were assessed via linear mixed effect models. Results: Data from 28 patients (average age 11.6 years, 46% male, average body mass index 30.9) and 128 controls (average age 11.1 years, 46% male, average body mass index 18.0) were analyzed. Patients were recruited between November 2018 and February 2020. For patients, the median compliance for the measurements ranged from 55% to 100% and the highest median compliance was observed for the smartwatch-related measurements (81–100%). Patients had a lower daily PA level (4,597 steps vs. 6,081 steps, 95% confidence interval [CI] 862–2,108) and peak PA level (1,115 steps vs. 1,392 steps, 95% CI 136–417), a higher nighttime HR (81 bpm vs. 71 bpm, 95% CI 6.3–12.3) and daytime HR (98 bpm vs. 88 bpm, 95% CI 7.6–12.6), a higher systolic BP (115 mm Hg vs. 104 mm Hg, 95% CI 8.1–14.5) and diastolic BP (76 mm Hg vs. 65 mm Hg, 95% CI 8.7–12.7), and a shorter sleep duration (difference 0.5 h, 95% CI 0.2–0.7) compared to controls. Conclusion: Remote monitoring via wearables in pediatric obesity has the potential to objectively measure the disease burden in the home-setting. The novel endpoints demonstrate significant differences in PA level, HR, BP, and sleep duration between patients and controls. Future studies are needed to determine the capacity of the novel digital endpoints to detect effect of interventions.

Accelerating vaccine trial conduct in a pandemic with a hot spot-based inclusion strategy using trial and epidemic simulation.

Clinical development of vaccines in a pandemic situation should be rigorous but expedited to tackle the pandemic threat as fast as possible. We explored the effects of a novel vaccine trial strategy that actively identifies and enrolls subjects in local areas with high infection rates. In addition, we assessed the practical requirements needed for such a strategy. Clinical trial simulations were used to assess the effects of utilizing these so-called "hot spot strategy" compared to a traditional vaccine field trial. We used preset parameters of a pandemic outbreak and incorporated realistic aspects of conducting a trial in a pandemic setting. Our simulations demonstrated that incorporating a hot spot strategy shortened the duration of the vaccine trial considerably, even if only one hot spot was identified during the clinical trial. The active hot spot strategy described in this paper has clear advantages compared to a "wait-and-see" approach that is used in traditional vaccine efficacy trials. Completion of a clinical trial can be expedited by adapting to resurgences and outbreaks that will occur in a population during a pandemic. However, this approach requires a speed of response that is unusual for a traditional phase III clinical trial. Therefore, several recommendations are made to help accomplish rapid clinical trial setup in areas identified as local outbreaks. The described model and hot spot vaccination strategy can be adjusted to disease-specific transmission characteristics and could therefore be applied to any future pandemic threat.

The impact of the global COVID-19 pandemic on the conduct of clinical trials: Return to normalcy by considering the practical impact of a structured ethical analysis.

During the outbreak of the COVID-19 pandemic many clinical trials were abruptly halted. Measures to contain the pandemic are currently taking effect and societies in general and healthcare systems in particular are considering how to return to normalcy. This opens up the discussion when and how clinical trials should be restarted while the COVID-19 pandemic has not yet resolved, and what should happen in case of a resurgence of the virus in the coming months. This article uses the four ethical principles framework as a structured approach to come to a set of practical, ethically grounded guidelines for halting and relaunching clinical trials during the COVID-19 pandemic. The framework applied provides a structured approach for all clinical trials stakeholders and thereby prevents unclear reasoning in a complex situation. While it is essential to prevent the virus from resurging and focus on developing a COVID-19 treatment as soon as possible, it is just as important to our society that we continue developing new drugs for other conditions. In this article we argue that the situation for clinical trials is not essentially different from the pre-COVID-19 era and that an overcautious approach will have negative consequences.