Cookies on this website

We use cookies to ensure that we give you the best experience on our website. If you click 'Accept all cookies' we'll assume that you are happy to receive all cookies and you won't see this message again. If you click 'Reject all non-essential cookies' only necessary cookies providing core functionality such as security, network management, and accessibility will be enabled. Click 'Find out more' for information on how to change your cookie settings.

Objectives: We applied principles for conducting economic evaluations of factorial trials to a trial-based economic evaluation of a cluster-randomised 2x2x2 factorial trial. We assessed the cost-effectiveness of atorvastatin, omega-3 fish oil and an action-planning leaflet, alone and in combination, from a UK NHS perspective. Methods: The Atorvastatin in Factorial with Omega EE90 Risk Reduction in Diabetes (AFORRD) trial randomised 800 patients with type 2 diabetes to atorvastatin, omega-3 or their respective placebos and randomised general practices to receive a leaflet-based action-planning intervention designed to improve compliance, or standard care. Sixteen-week outcomes for each trial participant were extrapolated for 70 years using the United Kingdom Prospective Diabetes Study Outcomes Model v2.01 (UKPDS-OM2). We analysed the trial as a 2x2 factorial trial (ignoring interactions between action-planning leaflet and medication), as a 2x2x2 factorial trial (considering all interactions), and ignoring all interactions. Results: We observed several qualitative interactions for costs and quality-adjusted life-years (QALYs) that changed treatment rankings. However, different approaches to analysing the factorial design did not change the conclusions. There was ≥99% chance that atorvastatin is cost-effective and omega-3 is not at a £20,000/QALY threshold. Conclusions: Atorvastatin monotherapy was the most cost-effective combination of the three trial interventions at a £20,000/QALY threshold. Omega-3 fish oil was not cost-effective, while there was insufficient evidence to draw firm conclusions about action-planning. Recently-developed methods for analysing factorial trials and combining parameter and sampling uncertainty were extended to estimate cost-effectiveness acceptability curves within a 2x2x2 factorial design with model-based extrapolation. Trial registration: ISRCT 76737502


Journal article


Value in Health



Publication Date



economic evaluation, type 2 diabetes, randomised controlled trial, individual patient simulation model, factorial design, lipids, adherence