ScHARR, University of Sheffield, Regent Court, Sheffield, UK.
Health Technol Assess. 2009 Sep;13 Suppl 2:15-21. doi: 10.3310/hta13suppl2/03.
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.
本文总结了证据审查组对阿替普酶治疗急性缺血性脑卒中的临床疗效和成本效益的评估报告，该评估符合许可适应证，基于制造商向国家卫生与临床优化研究所（NICE）提交的证据，作为单一技术评估（STA）流程的一部分。提交的临床证据包括几项随机对照试验，结果表明，在高度选择的患者中，在急性缺血性脑卒中发病后 3 小时内给予许可剂量的阿替普酶，与安慰剂相比，3 个月时死亡或依赖的风险降低具有统计学意义，尽管在第 7-10 天内症状性颅内出血的风险显著增加。国家神经病学与卒中研究所（NINDS）试验的数据表明，治疗的益处可持续到 6 个月和 12 个月。然而，观察性研究的数据表明，根据目前的许可协议，很少有急性缺血性脑卒中患者符合阿替普酶治疗的条件。特别是，许多患者因年龄而被排除在外，更多的患者因治疗仅限于发病后 3 小时内可以开始治疗的患者而被排除在外。制造商的提交内容包括一个状态转移模型，该模型评估了在发病症状出现后 3 小时内用阿替普酶治疗与标准治疗相比的影响，报告显示，在基本分析中，阿替普酶的成本低于标准治疗，且效果更好。通过对参数的单向敏感性分析，这一数值最高可达约 4000 英镑。提交内容中的概率敏感性分析表明，阿替普酶的成本效益比大于每获得 1 个质量调整生命年（QALY）超过 20000 英镑的可能性接近 1（0.99）。短期模型的结果表明，在 12 个月内，阿替普酶具有成本效益，增量成本效益比为每获得 1 个 QALY 增加 14026 英镑。通过对参数的单向敏感性分析，这一数值最高可达 50000 英镑。在 12 个月时，提交内容中的概率敏感性分析表明，阿替普酶的成本效益比大于每获得 1 个 QALY 超过 20000 英镑的可能性约为 0.7。NICE 于 2007 年 4 月发布的 STA 指南规定，只有在接受过急性卒中管理培训且经验丰富的医生在具备所需设施的中心使用时，才推荐阿替普酶治疗急性缺血性脑卒中。
