MODELING THE COST EFFECTIVENESS OF NEUROIMAGING-BASED TREATMENT OF ACUTE STROKE PATIENTS WITH UNKNOWN STROKE ONSET TIME
Purpose: Thrombolytic treatment (tissue-type plasminogen activator [tPA]) is only recommended for acute ischemic stroke patients with stroke onset time <4.5 hours due to higher bleeding risks with onset time >4.5 hours. tPA is not recommended when stroke onset time is unknown (14-28% of ischemic strokes). Magnetic resonance imaging (MRI) of the brain can be used to estimate stroke onset time with considerable accuracy. We projected health benefits, risks, and costs of image-based treatment decisions versus the current recommendation (no treatment) for acute stroke patients with unknown stroke onset time.
Methods: We developed a micro-simulation model that assigned patients a true stroke onset time from a beta distribution (average value 6.5 hours with uniform probability between 2.5-10.5 hours). Brain MRI used to estimate stroke onset time had estimated sensitivity and specificity of 0.62 and 0.78 respectively from the literature, cost $488, and delayed treatment by 30 minutes. True stroke onset time affected the impact of tPA on the probability of a favorable acute stroke outcome (modified Rankin score of 0-1 [mRS0-1]; odds ratio range 1.0-2.6 depending on true onset time) and the risk of major bleeding events (substantial intracerebral hemorhrage [sICH]; odds ratio range 3.5-8.5). Cost, utility, and disease progression parameters were estimated from published sources and depended on treatment status (tPA cost $16,740), mRS (utility values range 0.2-0.8), and sICH (54% fatal) outcomes. Discounted lifetime costs and health benefits (quality-adjusted life years [QALYs]) were projected for each strategy. In a sensitivity analysis, true stroke time was assumed to be left-skewed (average 4.8 hours with skewed beta distribution).
Results: With no treatment, 45.1% and 1.0% patients with unknown stroke time experienced mRS0-1 and sICH outcomes, respectively, with 5.125 lifetime QALYs and $86,949 lifetime costs; the image-based strategy resulted in 46.4% mRS0-1, 3.0% sICH, 5.150 QALYs, and $92,356 costs. The incremental cost-effectiveness ratio (ICER) for image-based treatment versus no treatment was $220,000/QALY. The ICER using a left-skewed beta distribution was $91,000/QALY. Results were sensitive to MRI sensitivity and specificity (Figure).
Conclusions: The cost-effectiveness of image-based treatment decisions versus the current recommendation of no tPA treatment for acute stroke patients with unknown onset time is sensitive to assumptions about true stroke onset time. Cost-effective image-based treatment (<$100,000/QALY) for these patients could be achieved with improved MRI diagnostic performance.