Methods for the economic evaluation of personalized medicine : a case study in advanced colorectal cancer

With the use of precision medicine in oncology, where choice of treatment is informed by the molecular characteristics of the disease, we expect to see heterogeneity in the effectiveness and costs of interventions. New precision medicine interventions are often costly and evidence from randomized controlled trials may not be available, yet decision-makers must be able to evaluate these interventions appropriately to inform efficient health resource allocation. The goal of my thesis is to explore methods to quantify the value and impact of identifying heterogeneity, using real-world observational data. The use of third-line anti-EGFR therapy (cetuximab and panitumumab) informed by RAS mutation status for patients with metastatic colorectal cancer is used as the example throughout the work. The analysis uses linked administrative data for a historical cohort of patients with metastatic colorectal cancer who were potentially-eligible for third-line systemic therapy. Using these data I conducted a cost-effectiveness analysis of anti-EGFR therapy informed by KRAS testing, and a cost-effectiveness analysis of panel-based expanded RAS testing vs. simple KRAS testing. I also conducted a literature review to identify and compare alternative frameworks for valuing heterogeneity-informed treatment decisions in the context of precision medicine. Based on this review, I selected the value of heterogeneity framework to evaluate alternative RAS-based subgrouping strategies to inform anti-EGFR therapy. The results of the analysis indicate that at the lower range of cost-effectiveness thresholds, anti-EGFR therapy would not be considered cost-effective regardless of subgrouping strategy. Value of heterogeneity analysis indicates that at a threshold of $100,000/LYG the value gained from subgroup-based decisions exceeds the costs of the genomic testing required to define the subgroups. Resolving uncertainty, or reducing the costs of testing and treatment, could provide considerable additional value. The value of heterogeneity framework can complement conventional methods for economic evaluation by describing and valuing the heterogeneity that arises with the use of precision medicine in a more comprehensive way. This research also demonstrates the strengths of using real-world data to conduct value of heterogeneity analysis. The precision medicine landscape is continuously evolving, and embracing new methods and sources of evidence will help decision-makers keep pace with these changes.Medicine, Faculty ofPopulation and Public Health (SPPH), School ofGraduat