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Background There is little systematic assessment of how total health expenditure is distributed across diseases and comorbidities. The objective of this study was to use statistical methods to disaggregate all publicly funded health expenditure by disease and comorbidities in order to answer three research questions: (1) What is health expenditure by disease phase for noncommunicable diseases (NCDs) in New Zealand? (2) Is the cost of having two NCDs more or less than that expected given the independent costs of each NCD? (3) How is total health spending disaggregated by NCDs across age and by sex? Methods and findings We used linked data for all adult New Zealanders for publicly funded events, including hospitalisation, outpatient, pharmaceutical, laboratory testing, and primary care from 1 July 2007 to 30 June 2014. These data include 18.9 million person-years and $26.4 billion in spending (US$ 2016). We used case definition algorithms to identify if a person had any of six NCDs (cancer, cardiovascular disease [CVD], diabetes, musculoskeletal, neurological, and a chronic lung/liver/kidney [LLK] disease). Indicator variables were used to identify the presence of any of the 15 possible comorbidity pairings of these six NCDs. Regression was used to estimate excess annual health expenditure per person. Cause deletion methods were used to estimate total population expenditure by disease. A majority (59%) of health expenditure was attributable to NCDs. Expenditure due to diseases was generally highest in the year of diagnosis and year of death. A person having two diseases simultaneously generally had greater health expenditure than the expected sum of having the diseases separately, for all 15 comorbidity pairs except the CVD-cancer pair. For example, a 60-64-year-old female with none of the six NCDs had $633 per annum expenditure. If she had both CVD and chronic LLK, additional expenditure for CVD separately was $6,443/$839/$9,225 for the first year of diagnosis/prevalent years/last year of life if dying of CVD; additional expenditure for chronic LLK separately was $6,443/$1,291/$9,051; and the additional comorbidity expenditure of having both CVD and LLK was $2,456 (95% confidence interval [CI] $2,238-$2,674). The pattern was similar for males (e.g., additional comorbidity expenditure for a 60-64-year-old male with CVD and chronic LLK was $2,498 [95% CI $2,264-$2,632]). In addition to this, the excess comorbidity costs for a person with two diseases was greater at younger ages, e.g., excess expenditure for 45-49-year-old males with CVD and chronic LLK was 10 times higher than for 75-79-year-old males and six times higher for females. At the population level, 23.8% of total health expenditure was attributable to higher costs of having one of the 15 comorbidity pairs over and above the six NCDs separately; of the remaining expenditure, CVD accounted for 18.7%, followed by musculoskeletal (16.2%), neurological (14.4%), cancer (14.1%), chronic LLK disease (7.4%), and diabetes (5.5%). Major limitations included incomplete linkage to all costed events (although these were largely non-NCD events) and missing private expenditure. Conclusions The costs of having two NCDs simultaneously is typically superadditive, and more so for younger adults. Neurological and musculoskeletal diseases contributed the largest health system costs, in accord with burden of disease studies finding that they contribute large morbidity. Just as burden of disease methodology has advanced the understanding of disease burden, there is a need to create disease-based costing studies that facilitate the disaggregation of health budgets at a national level., Author(s): Tony Blakely 1,2,*, Giorgi Kvizhinadze 1, June Atkinson 1, Joseph Dieleman 3, Philip Clarke 2,4 Introduction The Global Burden of Disease (GBD) has achieved the vision of a coherent [...]

Background The anti-human epidermal growth factor receptor 2 (HER2) monoclonal antibody trastuzumab improves outcomes in patients with node-positive HER2+ early breast cancer. Given trastuzumab's high cost, we aimed to estimate its cost-effectiveness by heterogeneity in age and estrogen receptor (ER) and progesterone receptor (PR) status, which has previously been unexplored, to assist prioritisation. Methods and Findings A cost-utility analysis was performed using a Markov macro-simulation model, with a lifetime horizon, comparing a 12-mo regimen of trastuzumab with chemotherapy alone using the latest (2014) effectiveness measures from landmark randomised trials. A New Zealand (NZ) health system perspective was adopted, employing high-quality national administrative data. Incremental quality-adjusted life-years for trastuzumab versus chemotherapy alone are two times higher (2.33 times for the age group 50-54 y; 95% CI 2.29-2.37) for the worst prognosis (ER-/PR-) subtype compared to the best prognosis (ER+/PR+) subtype, causing incremental cost-effectiveness ratios (ICERs) for the former to be less than half those of the latter for the age groups from 25-29 to 90-94 y (0.44 times for the age group 50-54 y; 95% CI 0.43-0.45). If we were to strictly apply an arbitrary cost-effectiveness threshold equal to the NZ gross domestic product per capita (2011 purchasing power parity [PPP]-adjusted: US$30,300; [euro]23,700; £21,200), our study suggests that trastuzumab (2011 PPP-adjusted US$45,400/[euro]35,900/£21,900 for 1 y at formulary prices) may not be cost-effective for ER+ (which are 61% of all) node-positive HER2+ early breast cancer patients but cost-effective for ER-/PR- subtypes (37% of all cases) to age 69 y. Market entry of trastuzumab biosimilars will likely reduce the ICER to below this threshold for premenopausal ER+/PR- cancer but not for ER+/PR+ cancer. Sensitivity analysis using the best-case effectiveness measure for ER+ cancer had the same result. A key limitation was a lack of treatment-effect data by hormone receptor subtype. Heterogeneity was restricted to age and hormone receptor status; tumour size/grade heterogeneity could be explored in future work. Conclusions This study highlights how cost-effectiveness can vary greatly by heterogeneity in age and hormone receptor subtype. Resource allocation and licensing of subsidised therapies such as trastuzumab should consider demographic and clinical heterogeneity; there is currently a profound disconnect between how funding decisions are made (largely agnostic to heterogeneity) and the principles of personalised medicine., Author(s): William Leung 1,2,*, Giorgi Kvizhinadze 1, Nisha Nair 1, Tony Blakely 1 Introduction Between 12% and 25% of breast cancer cases are human epidermal growth factor receptor 2 (HER2) [...]