Document Type
Article
Publication Date
5-19-2026
Publication Title
BMC Medicine
Abstract
Chronotherapy aims to maximise treatment efficacy while minimising side effects by scheduling treatment according to personal biological rhythms. In recent years, randomised clinical trials (RCTs) have been conducted to evaluate whether scheduled blood pressure interventions can improve patient outcomes. However, reports of time-of-day effects have attracted rebuttals and engendered methodological debate. A perfectly controlled chronotherapy trial (i.e., a trial that assesses the effect of assigning time of intervention) will never be feasible in the real world; yet some factors may be more critical to consider and control for than others. To advance the conversation about how best to evaluate the effects of antihypertensive chronotherapeutic interventions in RCTs, we discuss critical considerations for clinical trials of chronotherapy for hypertension and apply mathematical modelling to provide quantitative insights into the extent to which such factors may influence the detected effect size.
Volume
24
Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 International License.
Rights
© The Author(s) 2026
Version
Version of Record
Recommended Citation
Walch, Olivia; Rogers, Amy; Huang, Yitong P.; Ruben, Marc D.; Dyar, Kenneth A.; Flynn, Robert W. V.; Mackenzie, Isla S.; Manfredini, Roberto; Cappuccio, Francesco P.; and Pigazzani, Filippo, "Design Considerations for Hypertension Chronotherapy Trials: Insights from Experience and Modelling" (2026). Mathematics Sciences: Faculty Publications, Smith College, Northampton, MA.
https://scholarworks.smith.edu/mth_facpubs/209