This paper presents a summary of the evidence review group report into the 
clinical effectiveness and cost-effectiveness of alteplase for the treatment of 
acute ischaemic stroke, in accordance with the licensed indication, based upon 
the evidence submission from the manufacturer to the National Institute for 
Health and Clinical Excellence (NICE) as part of the single technology appraisal 
(STA) process. The submitted clinical evidence included several randomised 
controlled trials indicating that, in highly selected patients, alteplase 
administered at a licensed dose within 3 hours of the onset of acute ischaemic 
stroke is associated with a statistically significant reduction in the risk of 
death or dependency at 3 months compared with placebo, despite a significantly 
increased risk of symptomatic intracranial haemorrhage within the first 7-10 
days. Data from the National Institute of Neurological Disorders and Stroke 
(NINDS) trial suggest that the benefit of treatment is sustained at 6 and 12 
months. However, data from observational studies suggest that few patients with 
acute ischaemic stroke will be eligible for alteplase therapy under the terms of 
the current licensing agreement. In particular, many patients will be excluded 
by virtue of their age, and many more by the restriction of therapy to patients 
in whom treatment can be initiated within 3 hours of symptom onset. The 
manufacturer's submission included a state transition model evaluating the 
impact of treatment with alteplase within 3 hours of onset of stroke symptoms 
compared to standard treatment reporting that, in the base-case analysis, 
alteplase was both less costly and more effective than standard treatment. This 
increased to a maximum of approximately 4000 pounds upon one-way sensitivity 
analysis of the parameters. The probabilistic sensitivity analysis presented 
within the submission suggests that the probability that alteplase has a 
cost-effectiveness ratio greater than 20,000 pounds per quality-adjusted 
life-year (QALY) gained is close to 1 (0.99). The results of the short-term 
model demonstrate that alteplase is cost-effective over a 12-month period, with 
an incremental cost-effectiveness ratio of 14,026 pounds per QALY gained. This 
increased to a maximum of 50,000 pounds upon one-way sensitivity analysis of the 
parameters. At 12 months, the probabilistic sensitivity analysis presented 
within the submission suggests that the probability that alteplase has a 
cost-effectiveness ratio greater than 20,000 pounds per QALY gained is 
approximately 0.7. The guidance issued by NICE in April 2007 as a result of the 
STA states that alteplase is recommended for the treatment of acute ischaemic 
stroke only when used by physicians trained and experienced in the management of 
acute stroke and in centres with the required facilities.