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Title: What are the optimal treatment strategies in people of increased stroke risk due to carotid stenosis : using clinical trial and external data to evaluate long-term benefits and cost-effectiveness?
Author: Lokuge, Kusal
ISNI:       0000 0004 7971 614X
Awarding Body: University of Oxford
Current Institution: University of Oxford
Date of Award: 2018
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Introduction: Stroke, a major cause of disability and death worldwide, can be caused by carotid artery stenosis. Detection and treatment of carotid stenosis has substantial health and economic impact worldwide. It is therefore important to evaluate the long-term effects and cost-effectiveness of treatment methods for carotid stenosis, namely medical therapy (MT), carotid endarterectomy (CEA) in addition to MT, and carotid artery stenting (CAS) in addition to MT. Methods: The literature was systematically reviewed for economic evaluations comparing treatment methods for carotid stenosis, to summarise current evidence and identify limitations of available economic evaluations. Randomised Controlled Trials (RCTs) and large observational cohort studies were systematically reviewed to summarise information on the clinical effectiveness of treatment methods. Information from this evidence was then combined with information from the literature on quality of life and healthcare costs relevant to carotid stenosis patients, to inform a new decision analytical model, evaluating the cost-effectiveness of all available treatment methods for carotid stenosis patients in the UK. Results: There was a clear need in the literature for an economic evaluation comparing all available treatment methods for carotid stenosis in a single framework. Other limitations were identified relating to model structure, input parameters used, and reporting of results. Results synthesised from RCTs show that CEA has lower procedural stroke/death risks and lower overall stroke risks when compared to CAS, with differences mostly attributable to the larger number of minor strokes following CAS. When compared to MT alone, CEA reduced the risk of the combined endpoint of any stroke or procedural death. Observational studies showed that procedural stroke/death risks of CEA have decreased overtime, whilst procedural stroke/death risks of CAS patients appear to be stable. Results from the cost-effectiveness framework comparing all treatment methods show that, at willingness to pay for a quality adjusted life year (QALY) of £20,000, CEA in addition to MT is the most cost-effective strategy in patients up to the age of 75 years. MT alone was the most cost-effective option for patients 75 years or older. Treatment decisions based on the cost-effectiveness analysis remained the same when considered by gender or symptomatic status of patients. The value of information analysis indicated that further information about the relative post-procedural stroke risks of CEA plus MT vs MT alone is most valuable to reduce uncertainty in treatment decisions. Conclusion: The cost-effectiveness framework and evidence developed in this thesis addresses directly the limitations in the literature. It used information about procedural CEA risks in recent observational cohort studies and relative treatment effects from meta-analysis of RCTs, showing that optimal treatment decisions depend on the age of patients, with CEA plus MT being cost-effective in patients up to the age of 75 but MT alone likely to be more cost-effective in older people. These findings should be highly relevant in the development of future treatment guidelines.
Supervisor: Mihaylova, Borislava ; Gray, Alastair ; Halliday, Alison ; Bulbulia, Richard Sponsor: University of Oxford
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available