Setting The setting was secondary care. The economic analysis was conducted in Vancouver, Canada.

Transcription

1 Cost-utility analysis of tissue plasminogen activator therapy for acute ischaemic stroke Sinclair S E, Frighetto, Loewen P S, Sunderji R, Teal P, Fagan S C, Marra C A Record Status This is a critical abstract of an economic evaluation that meets the criteria for inclusion on NHS EED. Each abstract contains a brief summary of the methods, the results and conclusions followed by a detailed critical assessment on the reliability of the study and the conclusions drawn. Health technology The use of tissue plasminogen activator (t-pa) therapy for the treatment of acute ischaemic stroke. t-pa was given intravenously at a dose of 0.9 mg/kg to a maximum of 90 mg, initiated within 3 hours of stroke onset. Type of intervention Treatment. Economic study type Cost-utility analysis. Study population The study population consisted of a hypothetical cohort of 1,000 patients with ischaemic stroke, presenting to a hospital within 3 hours of the onset of stroke symptoms and with a mean age of 67 years. Setting The setting was secondary care. The economic analysis was conducted in Vancouver, Canada. Dates to which data relate The effectiveness data were gathered from studies published in Some of the resource data were gathered between March 1998 and October 1998, while some were derived from studies published between 1997 and The price year was Source of effectiveness data The effectiveness data were derived from a review of the literature, augmented by authors' assumptions. Modelling A Markov-based decision analytic model was created using DATA 3.5 software to simulate the costs and health outcomes assigned to each treatment strategy. Seven health states or functional disability Rankin scores were described. These were no symptoms (R0), no significant disability (R1), minimal disability (R2), moderate disability (R3), moderate to severe disability (R4), severe disability (R5), and death. The 30-year time horizon was chosen. Annual cycles appear to have been used. Outcomes assessed in the review The outcomes assessed in the review and used as model inputs were: the probability of intracranial haemorrhage (ICH); Page: 1 / 6

2 the distribution of patients by functional disability post-stroke level; the rates of stroke recurrence; and the probabilities of patient disposition at 3 months post-stroke to home, rehabilitation centres or long-term care facilities, stratified by the level of disability. Study designs and other criteria for inclusion in the review A recent large clinical trial has evaluated t-pa intravenously for the treatment of acute ischaemic stroke. This trial, the National Institute of Neurological Disorders and Stroke (NINDS) study, was the only study in which patients had been treated within 3 hours of onset of symptoms with either placebo or t-pa (see Other Publications of Related Interest). The NINDS study was a randomised, double-blind placebo-controlled trial that evaluated the short- and long-term outcomes of t-pa in 624 patients with acute ischaemic stroke. The probabilities of patient disposition by Rankin score at 3 months were derived from unpublished NINDS trial data. The second European Cooperative Acute Stroke Study (ECASS-II) was also used to estimate the stroke recurrence rate (Hacke et al., see Other Publication of Related Interest). This study was a randomised, double-blind placebo-controlled trial of thrombolytic therapy with intravenous alteplase in acute ischaemic stroke. The Statistics Canada database was used to estimate the probabilities of all-cause mortality, death due to stroke and non stroke all-cause mortality. Sources searched to identify primary studies Criteria used to ensure the validity of primary studies Methods used to judge relevance and validity, and for extracting data Number of primary studies included Two main primary studies were included in the analysis. Methods of combining primary studies Investigation of differences between primary studies The authors investigated and explained differences between the individual studies. The main difference was that the ECASS-II allowed 6 hours as the recruitment window, whereas the NINDS study allowed a 3-hour time window. Results of the review The probability of ICH was 6.4% in the t-pa group and 0.6% in the no t-pa group. The distribution of patients by functional disability post-stroke level was, respectively, in the t-pa and no t-pa groups: 15.8% versus 7.5% in R0 level, Page: 2 / 6

3 16.8% versus 10.1% in R1 level, 8.4% versus 9.4% in R2 level, 9.4% versus 9.4% in R3 level, 21.9% versus 28.3% in R4 level, 20.3% versus 25.1% in R5 level, and 7.4% versus 10.1% in death. The rate of stroke recurrence was 5.2% in both the t-pa and the no t-pa groups. The probabilities of patient disposition at 3 months post-stroke to home, rehabilitation centres or long-term care facilities stratified by the level of disability were tabulated in the paper. The probability of all-cause mortality was 0.67%. The probability of death due to stroke was 0.14%. The probability of non stroke all-cause mortality was 0.53%. Methods used to derive estimates of effectiveness The authors made several assumptions to estimate the outcomes. Estimates of effectiveness and key assumptions The authors assumed that: disposition status at 3 months post-stroke was equivalent to placement at 1 year; disability did not change because of reasons other than recurrent stroke; patients who experienced a recurrent stroke either retained the existing level of disability or decline, but not improve; and all patients were 67 years of age at the time of their index stroke. Measure of benefits used in the economic analysis The benefit measure used was the number of discounted quality-adjusted life-years (QALYs) gained. The utility values were assessed from a published study (Solomon et al., see Other Publication of Related Interest). The method used to derive the utility values was not reported. The benefits were discounted at a rate of 3%. Direct costs The perspective of the Canadian health care system was adopted. Only the direct costs were included. These were the acquisition costs of t-pa, the short-term hospitalisation costs per person, the annual facility costs per person, the annual costs of services per person and the cost of ICH. The facility costs included long-term care, rehabilitation and home care costs. The costs of services covered medical services, drugs and professional fees, devices, emergency health services and other community support. The institutional costs were derived from a review of 22 consecutive patients admitted to the authors' institution and who received t-pa between March 1998 and October Other published studies were used when the data were not available. The costs were obtained from the Patient Costing Department at Vancouver Hospital and Health Sciences Centre. The annual direct costs of ongoing stroke care were extrapolated from Page: 3 / 6

4 a published study conducted in Ontario. All the costs were expressed in 1999 Canadian dollars. The 30-year time horizon was used. The costs were discounted at an annual rate of 5%. Statistical analysis of costs No statistical analysis of the costs was performed. Indirect Costs The indirect costs were not included in the analysis. Currency Canadian dollars (Can$). Sensitivity analysis One-way and multivariate sensitivity analyses were performed for the cost of t-pa, short-term hospitalisation, the treatment of ICH and long-term outpatient care. The estimates were varied over a wide range of values (+/-25% of the base-case or 95% confidence interval when available). Estimated benefits used in the economic analysis In the hypothetical cohort, t-pa treatment resulted in 13,130 QALYs versus 9,670 QALYs with no t-pa treatment. The net benefit was 3,460 additional QALYs per 1,000 patients (3.46 QALYs per patient). Cost results For a hypothetical cohort of 1,000 patients, the estimated lifetime stroke costs were $Can103,100,000 in the t-pa group ($Can103,100 per patient) and $Can106,900,000 in the no t-pa group ($Can106,800 per patient). The lifetime cost-difference was $Can3,800,00 in favour of t-pa versus no t-pa ($Can3,800 per patient). Sensitivity analyses revealed that the model was robust to changes in the outcome or economic parameters. Synthesis of costs and benefits No incremental cost-effectiveness ratio was calculated as t-pa was found to be the dominant strategy (less costly and more effective). Authors' conclusions The use of tissue plasminogen activator (t-pa) therapy versus no t-pa resulted in a net saving over the patient's lifetime and an increase in the quality-adjusted life-years (QALYs). CRD COMMENTARY - Selection of comparators A justification was given for the comparator used, which referred to the standard treatment for stroke in the authors' setting. You should consider whether this is a widely used practice in your own setting. Validity of estimate of measure of effectiveness It was unclear whether a systematic review of the literature was conducted to derive the model input parameters. Two high-quality primary studies were used as the principal source of effectiveness data, which should consequently have high validity. However, the estimates and assumptions were not varied in the sensitivity analyses. In addition, the authors acknowledged that efficacy data rather than effectiveness data were included in the analysis, which may limit Page: 4 / 6

5 the validity of the results. Validity of estimate of measure of benefit The estimation of benefits was modelled. The decision analytic model used to derive a measure of heath benefit was appropriate. The utility values were assessed from a published study. However, the method used to derive the utility values (patient preferences or expert opinion) was not reported. This fact may limit the reliability of the QALY measurements. Validity of estimate of costs The authors limited the analysis to the direct costs. However, the exclusion of the indirect costs might have biased the results in favour of the standard stroke treatment. An indirect cost analysis would have enabled a societal perspective to be adopted. The authors acknowledged that the estimates of short-term hospitalisation costs were derived on the basis of a small sample size from a single centre. Thus, the estimates may not be representative of other institutions within Canada. Sensitivity analyses, however, were appropriately performed on the costs and the ranges of variation and results were reported in detail. Discounting was performed. Other issues The generalisability of the results was addressed. The authors made appropriate comparisons of their findings with those from other studies. The authors highlighted some limitations of their study and do not appear to have reported the results selectively. Implications of the study This model is useful for policy-makers, administrators and clinicians attempting to establish the role of t-pa for acute ischaemic stroke within their institutions and clinical practices. Source of funding Funded by the B.C. and Yukon Heart and Stroke Foundation. Bibliographic details Sinclair S E, Frighetto, Loewen P S, Sunderji R, Teal P, Fagan S C, Marra C A. Cost-utility analysis of tissue plasminogen activator therapy for acute ischaemic stroke. PharmacoEconomics 2001; 19(9): PubMedID Other publications of related interest National Institute of Neurological Disorders and Stroke rt-pa Stroke Study Group. Tissue plasminogen activator for acute ischaemic stroke. New England Journal of Medicine 1995;333: Hacke W, Kaste M, Fieschi C, et al. Second European-Australasian Acute Stroke Study Investigators. Randomised double-blind placebo-controlled trial of thrombolytic therapy with intravenous alteplase in acute ischaemic stroke (ECASS-II). Lancet 1998;352: Solomon NA, Glick HA, Russo CH, et al. Patient preferences for stroke outcomes. Stroke 1994;25: Fagan SC, Morgernstern LB, Petitta A, et al. Cost-effectiveness of tissue plasminogen activator for acute ischemic stroke. Neurology 1998;59: Page: 5 / 6

6 Powered by TCPDF ( Indexing Status Subject indexing assigned by NLM MeSH Canada /epidemiology; Cost-Benefit Analysis; Decision Support Techniques; Fibrinolytic Agents /economics /therapeutic use; Hospitalization /economics; Humans; Markov Chains; Myocardial Ischemia /drug therapy /economics /epidemiology; Quality-Adjusted Life Years; Tissue Plasminogen Activator /economics /therapeutic use AccessionNumber Date bibliographic record published 31/08/2004 Date abstract record published 31/08/2004 Page: 6 / 6