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The transition to university marks a point where young people may be open to changing health behaviours such as smoking, exercise, diet and alcohol intake. This study aimed to estimate the cost-effectiveness of an updated online health behaviour intervention for new university students in the UK – “U@Uni2”, compared with both a control (measurement only) scenario and with the original intervention (“U@Uni1”). The economic analysis, based on a randomized controlled trial, comprised a detailed costing analysis, a within-trial cost-effectiveness analysis and long-term economic modelling. Cost-effectiveness of the U@Uni2 trial was estimated using 6-month data on costs and health-related quality of life. An individual patient simulation model was adapted for long-term economic analysis of U@Uni2. Probabilistic sensitivity analysis and value of information analysis accounted for uncertainty in model inputs and identified key parameters. The U@Uni2 intervention costs £45.97 per person for full implementation, £10.43 per person for roll-out in a different institution and £3.03 per person for roll-out over five years. The U@Uni2 trial was not cost-effective because marginally fewer quality-adjusted life years (QALYs) were obtained in the intervention arm than the control. However, modelled over a lifetime, U@Uni2 is estimated to produce more QALYs than control but fewer than U@Uni1, primarily due to the effect of the interventions on smoking. Roll-out of U@Uni2 is highly likely to be more cost-effective than doing nothing (ICER = £536 per QALY, 86% probability cost-effective). Decision uncertainty occurs primarily around the effectiveness of the U@Uni2 intervention and is worth up to £3.24 m. The U@Uni2 intervention is highly likely to be cost-effective to roll-out when compared with doing nothing. The results suggest that preventing uptake of smoking is the key driver of QALY gain and should be the primary target of such interventions.       Key words: Alcohol, diet, exercise, smoking, health behavior, cost-effectiveness, economic evaluation, students, university.

The cost-effectiveness of an updated theory-based online health behavior intervention for new university students: U@Uni2