Abstract P6-08-11: UK OPTIMA-prelim study demonstrates economic value in more clinical evaluation of multi-parameter prognostic tests in early breast cancer
Authors: Hall Peter S , Smith Alison F , Vargas-Palacios Armando , Stein Robert C , Bartlett John , Bayani Jane , Marshall Andrea , Dunn Janet A , Campbell Amy F , Cunningham Carrie , Rooshenas Leila , Sobol Monika , Morgan Adrienne , Poole Christopher , Pinder Sarah E , Cameron David A , Stallard Nigel , Donovan Jenny , Hugh-Davies Luke , Earl Helena , Makris Andreas , Hulme Claire , McCabe Christopher 
Published: May 2015

Abstract
Background
There is uncertainty about the benefit of chemotherapy for some patients with ER-positive HER2-negative early breast cancer. Multi-parameter assays of gene expression may enhance the value of chemotherapy through personalised treatment decisions. An economic evaluation was undertaken in the context of the feasibility phase of an RCT (OPTIMA prelim) designed to validate prospectively the use of such an assay as a treatment decision tool in the UK National Health Service (NHS). The aim of the economic evaluation was to confirm value in an ongoing RCT and optimise its design for economic endpoints. Comparators included (i) All patients treated with chemotherapy, (ii) Oncotype DX, (iii) MammaPrint/BluePrint and (iv) Prosigna.
Methods
A model-based cost-effectiveness analysis was conducted to the standards of the UK National Institute for Care Excellence (NICE) reference case. A Markov model was constructed to simulate the care pathway of a cohort of patients with characteristics identified in the OPTIMA prelim study or, where unavailable, from the published literature. The costs (GBP) and benefits (QALYs) were estimated over a time horizon of the patient life-time. Alternative scenarios of recurrence rates and chemotherapy effect were explored in patients identified high or low risk by the tests and treated with and without chemotherapy. Scenarios included estimates based on the SWOG-8814 trial, the EBCTCG and outcomes forecasted using Adjuvant! Online. Uncertainty introduced by discrepancy in patient selection between tests was modelled using a Bayesian decision analytic framework. Probabilistic sensitivity analysis and value of information analysis was conducted using Monte Carlo simulation.
Results
There were 285 randomised patients. Multi-parameter analyses were performed on tumour samples and baseline factors were included in the model. The cost-effectiveness of all tests was uncertain. Uncertainty was predominantly driven by assumptions about long term recurrence rates in test-selected groups and the ability of tests to predict benefit from chemotherapy. The relationship between recurrence-free survival and life expectancy in test-selected groups and in patients who did or did not receive adjuvant chemotherapy was also important. The incremental cost-effectiveness ratio (ICER) for Oncotype DX compared with chemotherapy for all was cost-effective in many scenarios, ranging from GBP26,000 per QALY to resulting in increased QALYs with cost savings (dominate), depending on assumptions. The value of information analysis placed high societal value in further research into recurrence-free survival for test-directed chemotherapy, irrespective of the test evaluated.
Conclusion
There is substantial value in prospective comparative research into all tests evaluated, including long term outcomes, to resolve uncertainties in the clinical and economic optimal choice of test.
Acknowledgements
This project was funded by the National Institute for Health Research Health Technology Assessment (NIHR HTA) Programme (project number 10/34/01). The views and opinions expressed therein are those of the authors and do not necessarily reflect those of the HTA programme, NIHR, NHS or the Department of Health.
Citation Format: Peter S Hall, Alison F Smith, Armando Vargas-Palacios, Robert C Stein, John Bartlett, Jane Bayani, Andrea Marshall, Janet A Dunn, Amy F Campbell, Carrie Cunningham, Leila Rooshenas, Monika Sobol, Adrienne Morgan, Christopher Poole, Sarah E Pinder, David A Cameron, Nigel Stallard, Jenny Donovan, Luke Hugh-Davies, Helena Earl, Andreas Makris, Claire Hulme, Christopher McCabe. UK OPTIMA-prelim study demonstrates economic value in more clinical evaluation of multi-parameter prognostic tests in early breast cancer [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr P6-08-11.