Cost Effectiveness of PCSK9 Inhibitors for the Secondary Prevention of Cardiovascular Disease in Ireland: Considerations given to Population Heterogeneity

Abstract

The aim of this thesis was to evaluate the cost-effectiveness of PCSK9 inhibitors (alirocumab and evolocumab for the secondary prevention of CVD (cardiovascular disease) in Ireland. Also, to identify the subgroups of this population in which PCSK9 inhibitors might be deemed cost-effective. A systematic review of the literature was conducted. The results were included in a meta-analysis to quantify the comparative effectiveness of PCSK9 inhibitors versus standard of care. It was found that PCSK9 inhibitors reduce the time to non-fatal myocardial infarction (MI) and non-fatal stroke. No treatment effect on CVD death was observed over the time period of the clinical trials. But the quality of evidence was very low. An adjusted indirect treatment comparison between alirocumab and evolocumab was also conducted. Given the between-trial population heterogeneity, comparisons between PCSK9 inhibitors are uncertain. The similarity assumption was considered to hold sufficiently to justify the conclusion that there is no evidence of a difference in treatment effect between alirocumab and evolocumab. The interaction that strategic behaviour such as price negotiations can introduce to economic evaluations was identified for the first time A framework was presented to guide the economic evaluation process in the presence of an interaction. It was shown that failure to account for the interaction can lead to incorrect conclusions regarding the cost-effectiveness of interventions. Adoption of the framework is expected to increase population health through the increased recognition of cost-effective interventions. However, this conclusion does not consider the counterfactual that providers may present higher prices for drugs which would result in increased opportunity cost and a reduction in overall population health. Therefore, the net impact on population health is uncertain. The links between The Irish Longitudinal Study on Aging (TILDA) and the EQ-5D-3L were identified. Mapping the TILDA dataset to the EQ-5D-3L was identified as a pragmatic method of generating utilities in the Irish setting in the absence of directly observed evidence (the data gap). A mapping model between them was derived in a population with CVD. The mapping model was applied to the national TILDA population. Utility values for 23 subgroups of the secondary prevention population were derived. The use of patient level data means that heterogeneity in the health-related quality of life of the secondary prevention CVD population can be captured. Regression methods were used to estimate utility decrements for age, and to estimate chronic utility decrements for MI, stroke and multiple cardiovascular events. An incremental economic evaluation of PCSK9 inhibitors versus standard of care was conducted across 23 subgroups. A previously published economic model was adapted and used to extrapolate predicted costs and outcomes over a lifetime time horizon given the paucity of baseline risk data in the Irish setting. The economic model allowed the capture of the effect of population heterogeneity on baseline risk, treatment effect, costs and utility values. Regardless of whether direct or optimistic indirect treatment effects are applied, the results show that PCSK9 inhibitors are not cost-effective in the secondary prevention CV population in Ireland. An incremental evaluation of alirocumab and evolocumab to standard of care was also conducted. Neither alirocumab nor evolocumab are cost-effective relative to standard of care. However, when compared to evolocumab, alirocumab is likely to represent a cost-effective alternative. Important implications for policy and practice were identified.