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研究生:蔡民浤
研究生(外文):Ming-Hung Tsai
論文名稱:使用糖尿病之二線口服降血糖藥對於降低大血管病變之成本效益分析
論文名稱(外文):Cost-effectiveness of second-line agents added to metformin for cardiovascular risk reduction
指導教授:張睿詒張睿詒引用關係
口試委員:蕭斐元呂銘洋
口試日期:2018-07-03
學位類別:碩士
校院名稱:國立臺灣大學
系所名稱:健康政策與管理研究所
學門:醫藥衛生學門
學類:公共衛生學類
論文種類:學術論文
論文出版年:2018
畢業學年度:106
語文別:英文
論文頁數:104
中文關鍵詞:二線口服降血糖藥重大不良心血管事件成本效益馬可夫模型真實世界資料
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研究目的:
本研究評估使用二線口服降血糖藥物,對於降低糖尿病族群發生大血管病變的成本效益,並以藥品上市後之實證資料進行分析。

研究材料與方法:
本研究採回溯性世代研究,資料來源利用民國99~104年「衛生福利資料科學中心200萬人抽樣檔」。研究對象篩選出有穩定使用metformin,並且合併服用任一種糖尿病二線口服藥之第二型糖尿病患者,同時指標日期前從未發生過大血管事件者。依照用藥組合將研究對象分成五組:sulfonylureas組、acarbose組、meglitinides組、thiazolidinediones組、DPP4i組。當中,sulfonylureas組作為成本效益分析之對照組,因為sulfonylureas為過去最常見的二線藥品選擇。研究組確認後,分析患者於觀察期間內,發生重大不良大血管事件、死亡事件的發生率,同時計算各用藥組之相關醫療費用。接著將療效及費用數據套入馬可夫模型,以每年3.5%進行折舊,並進行敏感度分析。最後研究結果,得到不同用藥組合的終身成本效益。

研究結果:
研究結果顯示,模擬終生的情境下,除了metformin合併meglitinides類藥品之外,其他治療策略皆提升人年並且降低總醫療花費。也就是說,相較於metformin合併SU類藥品,metformin合併DPP4i、metformin合併thiazolidinediones、metformin合併acarbose為具有成本效益的藥物治療方案。具體來說,相較於SU組而言,使用DPP4i將增加0.94人年,並少花US$3,372元,ICER值為0.94元/LY;使用thiazolidinediones將增加2.53人年,並少花新US$2,580元,ICER值為2.35元/LY;使用acarbose將增加0.54人年,並少花US$11,283元,ICER值為0.54元/LY。敏感度分析後亦得到一致的結果。

結論與建議:
本研究提供糖尿病二線口服降血糖藥物治療的經濟實證,特別是當該決策著重於糖尿病相關之心血管併發症。在台灣目前的醫療環境下,相較於傳統治療metformin合併SU類藥品,建議使用較新推出的二線口服降血糖藥物(具體來說包含metformin合併DPP4i、metformin合併thiazolidinediones、metformin合併acarbose),對於降低大血管事件較具成本效益。研究結果顯示,因為這些二線藥物降低大血管病變的療效較好,長期模擬發現能夠提升終生的人年,並且降低終生的醫療花費,成為具備療效及成效的治療方案。不論是支付面或臨床面,採用具有成本效益的治療策略,方能減輕糖尿病所造成的疾病負擔。
Objective:
To evaluate the cost-effectiveness of adding relevant second-line agents to metformin for cardiovascular disease reduction in a type 2 diabetes population using post-marketing observational data.

Methods:
First, a retrospective national propensity score matched cohort was determined using the Taiwan National Health Insurance Research Database 2010-2015. Five metformin-based dual therapy groups were identified: metformin plus sulfonylureas, metformin plus acarbose, metformin plus meglitinides, metformin plus thiazolidinediones, and metformin plus DPP4 inhibitors. Metformin plus sulfonylureas was chosen as the reference group due to its conventional second-line therapy status. In our economic analysis, effectiveness measure included major adverse cardiovascular events and mortality, while cost measure considered direct medical cost. A Markov chain model was applied to project clinical and economic outcomes over a lifetime horizon, discounted at 3.5% per annum. An incremental cost-effectiveness ratio was determined. Sensitivity analysis was carried out to assess uncertainty in base-case assumptions.

Results:
In the base-case analysis, all treatments reduced costs, and all treatments except MET-MEG increased life-years. Thus MET-ALPHA, MEG-TZD, and MET-DPP4i were cost-effective compared to MET-SU. MET-ALPHA gained incremental benefits of 0.54 life-years at a cost-saving of $6,146 for an ICER of -$11,283 per LY. MET-TZD achieved incremental benefits of 2.41 life-years with a cost-saving of $2,085 for an ICER of -$8,64 per LY. MET-DPP4i achieved incremental benefits of 0.94 life-years at a cost-savings of $3,161 for an ICER of -$3,372 per LY. Results were consistent across a range of sensitivity analyses.

Conclusion:
This study provided empirical economic evidence to inform the choice of second-line agents, especially when CVD is considered important. Under present conditions in Taiwan, we would give preference to adding novel second-line agents to metformin for those who fail monotherapy, as compared to conventional MET–SU therapy. Antidiabetic drugs with superior cardiovascular profiles (such as DPP4 inhibitors, thiazolidinediones, and alpha-glucosidase inhibitors) demonstrate modest life-year gains and lower costs over time. We anticipate an appropriate use of these cost-effective treatment options will help payers and physicians mitigate the growing burden of diabetes.
Abstract ii
Chapter 1 – Introduction 1
1.1 Study context 1
1.2 Objective 4
Chapter 2 – Literature Review 5
2.1 Burden of diabetes 5
2.2 State of diabetes drug therapy 18
2.3 Approach to cost-effectiveness analysis 46
Chapter 3 – Methodology 56
3.1 Study design 56
3.2 Data source 58
3.3 Study population 59
3.4 Outcome of interest 64
3.5 Analytical approach 66
Chapter 4 – Results 71
4.1 Baseline of study groups 71
4.2 Primary analysis 74
Chapter 5 – Discussion 82
Chapter 6 – Conclusion 88
Reference 89
Appendix – Operational definition of variables 101
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