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Title: Evaluating cost effectiveness of precision cancer medicine approaches and the economic burden of colorectal cancer
Author: Henderson, Raymond
ISNI:       0000 0004 8504 3105
Awarding Body: Queen's University Belfast
Current Institution: Queen's University Belfast
Date of Award: 2019
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As the understanding of the biology of cancer intensifies, biomarkers with the potential to guide precision cancer medicine (PCM) are discovered with increasing regularity. Yet the cost-effectiveness of the biomarker-guided PCM strategy is rarely evaluated. Utilising colorectal cancer (CRC) as a bellwether for PCM implementation, I conducted a systematic review of health economic analyses of molecular biomarkers (MBM) to stratify CRC patients for PCM in high-income countries. This analysis found that: 1. Oncotype DX® is cost-effective in sparing treatment toxicity. 2. Dihydropyrimidine dehydrogenase gene (DPYD) status testing may be cost-effective to avoid 5-Fluorouracil (5-FU) toxicity. 3. Uridine 5'-diphospho-glucuronosyltransferase family 1 member A1 gene (UGT1A1) polymorphism status is not cost-effective in guiding irinotecan dosing. 4. The cost effectiveness of testing of KRAS/NRAS mutational status for guiding cetuximab or panitumumab therapy is inconclusive. Overall, the systematic review revealed that there was a paucity of cost-effectiveness studies in CRC to support biomarker-enriched PCM approaches. To discern the real-world impact that PCMs and other therapeutic modalities are having on CRC survival, the economic burden of CRC in Europe for the year 2015 was determined by an enhanced cost-of-illness study, covering the EU27, together with the United Kingdom, Iceland, Norway, Switzerland, Serbia and Turkey (EUR33). CRC costs in 2015 were €21.9bn, broken down as follows: healthcare costs: €7bn (32% of overall costs); mortality costs: €5.7bn (26%); morbidity costs: €7bn (32%); informal care costs: €2.2bn (10%). Costs for managing a CRC patient varied significantly across each country, as did hospital care costs. Amongst overall healthcare costs, pharmaceutical costs represented the second largest expenditure after hospital care costs, and in several countries pharmaceutical costs were higher than hospital costs. The proportion of total healthcare expenditure on CRC was notably highest in Central and Eastern European countries in terms of percentage spent: conversely, these countries experienced the lowest CRC survival rates. Finally, as biomarker guided continuous cetuximab (CC) and intermittent cetuximab (IC) demonstrated equivalent clinical efficacy in treating advanced CRC in the COIN-B trials, I undertook a retrospective cost-minimization analysis to determine which therapy was the least costly. By employing both partition survival modelling (PSM) and Markov chain Monte Carlo (MCMC) simulation, IC therapy did prove to be the dominant therapy when compared to CC therapy, with a cost reduction of £33,679 (by PSM) or £29,708 (by MCMC) per patient. In addition to the cost savings realised by IC therapy, the intermittent strategy allows for less invasive tumour monitoring during treatment and the opportunity for tumours to potentially re-sensitise to cetuximab treatment. This thesis demonstrates how viewing cancer and its treatment through a health economic lens can provide particular insights on the economic burden of this common disease and inform innovative precision medicine approaches to deliver robust but affordable cancer control for patients and society.
Supervisor: French, Declan ; Lawler, Mark Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available
Keywords: Economic evaluation ; Precision medicine ; Colorectal cancer