DEcrease STress through RESilience training for Students (DESTRESS) Study: Protocol for a randomized controlled trial nested in a longitudinal observational cohort study

Introduction: Chronic stress and burnout are highly prevalent among academically trained healthcare pro-fessionals, negatively affecting their well-being and capacity to engage in their work. Resilience to stress de-velops early in one's career path, hence offering resilience training to university students in these professions is one approach to fostering well-being and mental health. The aim of this study is to assess whether offering mindfulness-based resilience training to university students in healthcare professions reduces their perceived chronic stress.Methods and analysis: The study has a hybrid design combining a longitudinal observational cohort with a nested randomized controlled trial (RCT) with sequential multiple assignment and multistage adaptive interventions while taking participants' preferences into account. All students in healthcare related programmes at the Eras-mus University Rotterdam are invited to participate. Within the observational cohort, students with a score of 14 or higher on the Perceived Stress Scale (PSS) are invited to take part in the RCT (n = 706). Eligible participants are randomized to control or active intervention in a ratio of 1:6. Those randomized to the control group and non-randomized participants in the cohort receive passive web-based psychoeducation about chronic stress and burnout through referral to specific websites. Participants randomized to the intervention group receive one of 8 active mindfulness-based interventions. They select a rank order of 4 preferred interventions and are randomized across these with equal probability. Non-response to the intervention is followed by sequential randomized assignment to another intervention, for a total maximum of 3 sequential interventions. All participants receive questionnaires at baseline, before and after each 8-week intervention period, and at 1-and 2-year follow-up. The primary outcome is perceived chronic stress measured with the PSS. Secondary outcomes include mental well-being, burnout, quality of life, healthcare utilization, drug use, bodyweight, mental and physical stress-related symptoms, resilience, and study progress.Ethics and registration: Approval from the Medical Ethics Review Committee was obtained under protocol number MEC-2018-1645. The trial is registered in the Netherlands National Trial Register by registration number NL7623, 22/03/2019, https://www.trialregister.nl/.