Centre for Reviews and Dissemination, University of York, UK.
Health Technol Assess. 2009 Nov;13(58):1-265, iii-iv. doi: 10.3310/hta13580.
To evaluate the clinical effectiveness (including adverse events) and cost-effectiveness of antivirals for the treatment of naturally acquired influenza for 'at-risk' and otherwise healthy populations.
Eleven electronic databases (MEDLINE, EMBASE, Cumulative Index to Nursing and Allied Health Literature, Pascal, Science Citation Index, BIOSIS, Latin American and Caribbean Health Sciences, Cochrane Database of Systematic Reviews, Cochrane Central Register of Controlled Trials, Database of Abstracts of Reviews of Effects, and Health Technology Assessment Database) were searched from October 2001 to November 2007. A supplementary search was undertaken in June 2008 for information relating to drug resistance during the 2007-8 influenza season.
Systematic reviews of the evidence on the clinical effectiveness and cost-effectiveness of antivirals for the treatment of influenza were undertaken. Twenty-nine randomised controlled trials comparing antivirals with each other, placebo, or best symptomatic care were included in the evaluation of clinical effectiveness in patients presenting with an influenza-like illness (ILI). Primary outcomes were measures of symptom duration (median time to alleviation of symptoms and median time to return to normal activity). Incidence of complications, mortality, hospitalisations, antibiotic use (as a surrogate for complications) and adverse events was also assessed. In addition, an independent decision model was developed to evaluate the cost-effectiveness of antiviral treatment from the perspective of the UK NHS.
Amantadine was excluded at an early stage, owing to a lack of any new trials that met the inclusion criteria and the limitations of the existing evidence. The review therefore focused on the neuraminidase inhibitors (NIs) oseltamivir and zanamivir, both of which were found to be effective in reducing symptom duration (zanamavir by 0.5-1.0 days and oseltamivir by 0.5-1.5 days). However, the effect sizes were often small and unlikely to be clinically significant in many cases, particularly in healthy adults. For the at-risk subgroups, effect sizes for differences in symptom duration were generally larger, and potentially more clinically significant, than those seen in healthy adults (median duration of symptoms reduced by 1-2 days with zanamivir and 0.50-0.75 days with oseltamivir). However, there was greater uncertainty around these results, with estimates often failing to reach statistical significance. The most consistent data and strongest evidence related to antibiotic use, with both zanamivir and oseltamivir resulting in statistically significant reductions in antibiotic use. In general, the estimates from the cost-effectiveness model were more favourable in at-risk populations (including adults and children with comorbid conditions and the elderly) compared with otherwise healthy populations. Zanamivir was the optimal NI treatment in each of the at-risk populations considered, and oseltamivir was optimal for healthy populations (both adults and children).
The clinical effectiveness data for population subgroups used to inform the multiparameter evidence synthesis and cost-effectiveness modelling were, in places, limited and this should be borne in mind when interpreting the findings of this review. Trials were often not designed to determine clinical effectiveness in population subgroups and hence, although the direction of effect was clear, estimates of differences in symptom duration tended to be subject to greater uncertainty in subgroups. Despite some concerns, the use of NIs in at-risk populations appeared to be a cost-effective approach for the treatment of influenza. Well-designed observational studies might also be considered to evaluate the clinical course of influenza in terms of complications, hospitalisation, mortality and quality of life, as well as the impact of NIs.
评估抗病毒药物治疗“高危”和健康人群自然获得性流感的临床疗效（包括不良反应）和成本效益。
2001 年 10 月至 2007 年 11 月，11 个电子数据库（MEDLINE、EMBASE、累积索引护理和联合健康文献、Pascal、科学引文索引、生物科学、拉丁美洲和加勒比健康科学、Cochrane 系统评价数据库、Cochrane 对照试验注册中心、疗效评价文摘数据库和卫生技术评估数据库）进行了检索。2008 年 6 月，针对 2007-08 流感季节药物耐药性相关信息进行了补充检索。
对抗病毒药物治疗流感的临床疗效和成本效益进行了系统评价。纳入了 29 项比较抗病毒药物与安慰剂或最佳对症治疗的随机对照试验，评估了出现流感样疾病（ILI）患者的临床疗效。主要结局是症状持续时间（症状缓解的中位数时间和恢复正常活动的中位数时间）的测量。还评估了并发症、死亡率、住院、抗生素使用（作为并发症的替代指标）和不良反应的发生率。此外，还从英国国家医疗服务体系的角度开发了一个独立的决策模型来评估抗病毒治疗的成本效益。
由于缺乏符合纳入标准的新试验和现有证据的局限性，金刚烷胺在早期就被排除在外。因此，本研究重点关注神经氨酸酶抑制剂（NI）奥司他韦和扎那米韦，两者均能有效缩短症状持续时间（扎那米韦缩短 0.5-1.0 天，奥司他韦缩短 0.5-1.5 天）。然而，这些效果通常很小，在许多情况下，特别是在健康成年人中，可能没有临床意义。对于高危亚组，症状持续时间差异的效果大小通常更大，且可能更具有临床意义（与健康成年人相比，使用扎那米韦和奥司他韦可分别将症状持续时间缩短 1-2 天和 0.50-0.75 天）。然而，这些结果存在更大的不确定性，估计值往往无法达到统计学意义。与抗生素使用相关的最一致和最有力的数据和证据，扎那米韦和奥司他韦均能显著减少抗生素的使用。一般来说，在考虑的高危人群（包括患有合并症的成年人和儿童以及老年人）中，来自成本效益模型的估计结果更为有利。在每个考虑的高危人群中，扎那米韦都是最佳的 NI 治疗药物，而奥司他韦是健康人群（包括成年人和儿童）的最佳选择。
用于多参数证据综合和成本效益建模的人群亚组的临床疗效数据在某些方面受到限制，在解释本综述的结果时应考虑到这一点。试验通常不是为了确定人群亚组的临床疗效而设计的，因此，尽管疗效的方向很明确，但症状持续时间差异的估计往往在亚组中更具不确定性。尽管存在一些担忧，但在高危人群中使用 NIs 似乎是一种治疗流感的具有成本效益的方法。也可以考虑进行良好设计的观察性研究，以评估流感在并发症、住院、死亡率和生活质量方面的临床过程，以及 NIs 的影响。
