title: Alteplase for the treatment of acute ischaemic stroke: a NICE single technology appraisal; an evidence review group perspective.
abstract: The National Institute for Health and Care Excellence (NICE) invited Boehringer Ingelheim GmbH, the manufacturer of alteplase, to submit evidence for the clinical and cost-effectiveness of alteplase for the prevention of strokes within a 0-4.5 h window. The comparator was standard medical and supportive management that does not include alteplase. This paper provides a description of the company submission, the Evidence Review Group (ERG) review and NICE's subsequent decisions. Clinical effectiveness evidence for alteplase was derived from 5 trials. For the 3-4.5 h treatment window, alteplase did not show a statistically significant treatment effect on death or dependency at three months follow-up. For the 0-4.5 h treatment window data from a meta-analysis of 3 trials indicated that the reduction of death and dependency was statistically significant. In both cases there was a significant increase in symptomatic intracranial haemorrhage. The economic model described in the manufacturer's submission was considered by the ERG to meet the NICE reference case. The model structure was considered to be appropriate and the ERG has no major concerns regarding the selection of data used within the model. The incremental cost-effectiveness ratios (ICER) for all treatment windows were well below accepted willingness to pay thresholds. The ERG had no major concerns regarding the completeness of the submission or the robustness of the evidence presented. For all treatment windows considered, alteplase was found to be cost-effective compared with standard treatment.
authors.affiliation: School of Health and Related Research, University of Sheffield, Sheffield, S1 4DA, UK, m.w.holmes@shef.ac.uk.
authors.forename: Michael
authors.initials: M
authors.lastname: Holmes
authors.forename: Sarah
authors.initials: S
authors.lastname: Davis
authors.forename: Emma
authors.initials: E
authors.lastname: Simpson
mesh_terms: D002545:Brain Ischemia / Q000188:drug therapy* / Q000191:economics; D003362:Cost-Benefit Analysis; D005343:Fibrinolytic Agents / Q000008:administration & dosage / Q000191:economics / Q000627:therapeutic use; D006801:Humans; D020300:Intracranial Hemorrhages / Q000453:epidemiology; D018803:Models, Economic; D020521:Stroke / Q000188:drug therapy* / Q000191:economics; D013673:Technology Assessment, Biomedical; D013997:Time Factors; D010959:Tissue Plasminogen Activator / Q000008:administration & dosage / Q000191:economics / Q000627:therapeutic use*
chemical_list: D005343:Fibrinolytic Agents; D010959:Tissue Plasminogen Activator