| 摘要: | 背景與目的：抗病毒藥物被建議用於治療有類流感症狀的病人，尤其是在社區流行流行性感冒及SRAS-CoV-2病毒時。然而，哪一種抗病毒藥物的治療結果最好、安全性最佳，及用於治療流行性感冒的成本效益，目前仍不清楚。
研究方法：本研究分成三個部分，第一部分利用系統性綜論（systematic review）與網絡統合分析（network meta-analysis）方法綜整抗病毒藥物，包括zanamivir、baloxavir、oseltamivir及peramivir等的療效與安全性；第二部分利用決策樹模式（decision-tree model）進行抗病毒藥物與常規照護的成本效益分析（cost-effectiveness analysis, CEA）；第三部分，根據國際病人決策輔助工具標準，開發應用於共享決策的決策輔助工具（decision aids）。
研究結果：第一部分共納入26項隨機分派研究，11,897位受試者，在與常規照護比較的研究中，高品質證據顯示，zanamivir與最短的症狀緩解所需時間有關（危險比值0.67，95%信賴區間0.58至0.77）；中等證據品質顯示，baloxavir與最低的併發症風險有關（風險比值0.51，95%信賴區間0.32至0.80）。安全性方面，相較於安慰劑，中等證據品質顯示，baloxavir與最低的整體不良事件風險有關（風險比值0.84，95%信賴區間0.74至0.96）。除了oseltamivir之外，其他抗病毒藥物與噁心、嘔吐之間的關聯性不強，代表oseltamivir有比較高發生噁心（風險比值1.82，95%信賴區間1.38至2.41）、嘔吐（風險比值1.88，95%信賴區間1.47至2.41）的風險。且並未發現顯著的統計異質性或不一致性。第二部分，開發一個決策樹模式並以14天的時間範圍、健康照護付費者角度比較抗病毒藥物與常規照護對罹患流行性感冒病人的成本效益，baloxavir 40/80 mg在比較的五種治療選項中符合成本效益的機率最高。在付費意願設定為10,000美元時，其符合成本效益的機率超過70%。四種抗病毒藥物相較於常規照護，淨貨幣利益（net monetary benefit）皆為正數，baloxavir 40/80 mg 的遞增淨效益最高（861美元），接著是peramivir 300 mg（617美元）、zanamivir 10 mg（597美元）、oseltamivir 75 mg（504美元），最後是peramivir 600 mg（250美元）。本研究開發一個適用於流感病人考量抗病毒藥物選擇，且符合國際標準的病人決策輔助工具。開發過程納入病人、決策工具研發者、感染專科醫師及決策專家代表。在使用者測試中，參與者發現該輔助工具是可接受的且有利於決策。
結論：抗病毒藥物與症狀緩解所需時間縮短及流感併發症風險下降，有顯著關聯性，但彼此之間差異不大，zanamivir可能與最短的症狀緩解所需時間有關、baloxavir可能與最低的流感併發症風險有關，而使用oseltamivir與較高的噁心嘔吐副作用風險有關。Baloxavir 40/80 mg在經濟分析中符合成本效益的機率最高。實證為基礎的決策輔助工具有利於治療選項的決策進行。
Background and objectives：Antiviral agents were recommended to treat patients with influenza-like illness, especially during influenza and SARS-CoV-2 pandemics. However, questions about which treatment is associated with the best outcomes, fewest adverse events and their cost-effectiveness remain.
Methods：This study was divided into three parts. In the first part, we conducted a systematic review and network meta-analysis evaluating efficacy and safety of antiviral agents, including zanamivir, baloxavir, oseltamivir, and peramivir in the management of influenza. In the second part, an economic evaluation based on a decision-tree model comparing antiviral agents and usual care alone was performed. The third part was the development of an evidence-based decision aid that compatible with the criteria of the International Patient Decision Aid Standards.
Results：A total of 26 trials were identified that investigated antiviral drugs; these trials included 11,897 participants. Of all treatments comparing with placebo in efficacy outcomes, high-quality evidence indicated that zanamivir was associated with the shortest TTAS (hazard ratio, 0.67; 95% CI, 0.58-0.77), while baloxavir was associated with the lowest risk of influenza-related complications (risk ratio [RR], 0.51; 95% CI, 0.32-0.80) based on moderate-quality evidence. There was no strong evidence of associations with risk of nausea or vomiting among all comparisons, except for 75 mg oseltamivir, which was associated with greater occurrence of nausea (RR, 1.82; 95% CI, 1.38-2.41) and vomiting (RR, 1.88; 95% CI, 1.47-2.41). No significant statistical heterogeneity and inconsistency was identified. A decision-analysis model was developed with a fourteen-day time horizon to assess the cost-effectiveness of various antiviral agents compared with usual care from healthcare payer perspectives. Baloxavir 40/80 mg had the highest probability of being the most cost-effective of the five selected for comparison. It had a probability close to 70% in the 10,000 USD of willingness to pay. All antiviral agents have a positive net monetary benefit compared with usual care. Baloxavir had the highest incremental net benefit (861 USD), followed by peramivir 300 mg (617 USD), zanamivir 10 mg (597 USD), oseltamivir 75 mg (504 USD), and peramivir 600 mg (250 USD). A decision aid for influenza patients considering antiviral agents using the International Patient Decision Aid Standards. The development process involved patients, decision aid developers, infection specialist, and decision-making experts. In user testing, participants found the decision aid acceptable and helpful to facilitate decision making.
Conclusion：All 4 antiviral agents assessed were associated with shortening TTAS; zanamivir was associated with the shortest TTAS, and baloxavir was associated with reduced rate of influenza-related complications. Baloxavir had the highest probability to be cost-effective in the economic evaluation. An evidence-based decision-aid was developed to facilitate decision-making with regard to therapeutic options. |
