The health economics of haemochromatosis

Haemochromatosis is one of the most common autosomal recessive disorders amongst populations of northern European ancestry. It is a condition characterised by iron overload, which, if untreated, contributes to morbidity and mortality. As diagnosis is often delayed owing to the non-specific nature of early symptoms, population screening programs have been suggested to reduce the consequential burden of disease. To date, a paucity of robust health economic evidence regarding haemochromatosis screening has been cited as a key barrier to the establishment of such programs internationally. This thesis investigates and generates health economic evidence for haemochromatosis and related interventions, with a focus on population screening programs. Chapter 1 presents a general overview of haemochromatosis and health economic concepts pertinent to this thesis. Chapter 2 presents a systematic review of all health economic evidence regarding haemochromatosis screening and related interventions. Most of the evidence identified in the review related to population screening programs. The economic methodologies employed and the quality of epidemiologic evidence incorporated into these models were flawed in most studies, reducing their validity and generalizability. The gaps in current knowledge that were identified in this review guided the subsequent direction of this thesis. The systematic review did not identify any robust health state utility value data for haemochromatosis. Whilst four studies included in the review incorporated utility values into cost-effectiveness models, these were set at unrealistically high levels, with no description of the source of these provided. Chapter 3 aimed to robustly quantify the quality of life burden associated with haemochromatosis by measuring health state utility values. A national, online survey of people with haemochromatosis was conducted, which allowed for calculation of utilities for different categories of severity of haemochromatosis. These utility values, which provide insight into the quality of life impacts of haemochromatosis, were incorporated into the population screening model. In the absence of published literature quantifying the economic burden associated with haemochromatosis, a national cost of illness study was undertaken, and is reported in Chapter 4. Costs were estimated from the patient, government and societal perspectives, with societal costs extrapolated to the Australian population. These costs are the first to be published that quantify the economic burden of haemochromatosis. Whilst Chapters 3 and 4 provide information on the size of the burden associated with haemochromatosis, Chapter 6 identifies strategies to address this. Chapter 5 provides a detailed description of the construction and validation of the health economic model for screening for haemochromatosis. A state-transition Markov model using probabilistic decision analysis was constructed and validated for the Australian adult population of northern European ancestry. Chapter 6 presents the results generated from the health economics model. The target populations were males aged 30 years and females aged 45 years, both of northern European ancestry, and neonates irrespective of ancestry. Three population screening strategies (genotyping with a blood sample, genotyping with a buccal sample, sequential screening with two consecutive iron studies and confirmatory HFE genotyping) were modelled for adults and one for neonates (HFE genotyping). The current status quo was the comparator, which comprises a combination of cascade and opportunistic screening. From the government perspective, genotyping with a blood sample was the most cost-effective approach for males; for females, sequential screening was considered to be the most cost-effective. For male and female neonates, screening was associated with cost savings and increased effectiveness, thereby dominating the current status quo. This thesis presents a range of studies that were conducted to address the substantial knowledge gaps identified in the systematic review. Both the health state utility data and cost of illness data can be used to populate future health economic models regarding haemochromatosis interventions. The results of the modelling work provide medical and reimbursement decision-makers with robust data when considering future resource allocation decisions pertaining to screening for haemochromatosis.