Health economic considerations
The economic evaluation for stage I of the trial will evaluate the relative cost-effectiveness of the two treatment frequencies over a 12-month period. The incremental cost per quality-adjusted life-year (QALY) gained will be calculated as recommended by the National Institute for Health and Care Excellence (NICE) [Resource use will be collected at baseline for the preceding 12 weeks and every 12 weeks thereafter from patient records and directly from participants via a modified version of the Client Service Receipt Inventory (CSRI) [Parameter uncertainty will be addressed using standard boot-strapping techniques and sensitivity analyses performed for any assumptions made. Further details will be described in the statistical and health economic analysis plan.A lifetime decision analytic model will be constructed using information collected in stage I and stage II for those arms that are carried forward, to estimate the relative cost-effectiveness of the different treatment frequencies.