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研究生： 陳彥廷
Chen, Yen-Ting
論文名稱： 二線口服降血糖藥對糖尿病大血管病變之醫療成本效益分析
Analysis of cost effectiveness on add-on oral hypoglycemic agents and diabetes related macrovascular complications
指導教授： 歐凰姿
Ou, Huang-Tz
學位類別： 碩士
Master
系所名稱： 醫學院 - 臨床藥學與藥物科技研究所
Institute of Clinical Pharmacy and Pharmaceutical sciences
論文出版年： 2014
畢業學年度： 102
語文別： 中文
論文頁數： 138
中文關鍵詞： 二線口服降血糖藥 、成本效益 、大血管併發症 、馬可夫模型 、敏感性分析
外文關鍵詞： add-on oral hypoglycemic agents (OHAs), cost effectiveness, macrovascular complication event, markov model, sensitivity anslysis
相關次數： 點閱：136  下載：5 
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    • 研究背景
    實證顯示台灣糖尿病患者的直接醫療支出為非糖尿病患者的4.3倍，而此數據相較於世界衛生組織所報告的2~3倍是為更高。近年來，新藥理機轉的口服降血糖藥(例如：acarbose, meglitinides, thiazolidinedione等)陸續納入台灣健保給付，建議用於傳統第一線metformin控制不佳所增加之二線治療，為患者提供了更多治療上的選擇。然而，新藥理機轉的口服降血糖藥的每日耗用價格較傳統二線治療(sulfonylurea, SU)為高，因此對於二線口服降血糖藥（add-on oral hypoglycemic agents; 以下簡稱add-on OHAs）預防糖尿病併發症之醫療成本效益評估是需要的。而目前大部分的藥事經濟研究都是利用國外臨床試驗數據(efficacy)所模擬出來的結論，反之利用藥品上市後醫療效益的資料(effectiveness)於成本效益分析的文獻是較為缺乏，更遑論台灣本土的藥事經濟效益分析。

    研究目的
    1、 Add-on OHAs對於糖尿病心血管併發症之醫療效益分析
    2、 Add-on OHAs對於糖尿病心血管併發症之經濟效益分析

    研究方法
    本研究為回溯性世代研究，主要資料為民國89~99年「全民健康保險研究資料庫2010年承保百萬人抽樣歸人檔」。本研究收錄有穩定使用metformin合併任一種add-on OHAs之第二型糖尿病患者，並排除有第一型糖尿病診斷紀錄者、觀測期間內穩定使用胰島素者、無metformin合併add-on OHAs之處方紀錄者、指標日期前曾發生欲觀測大血管事件者。篩選出主要研究族群後，接著即可觀察患者於觀察期間是否有發生大血管事件，並分析各用藥組之大血管事件發生率，同時計算各用藥組之相關醫療處置花費，並將相關數據套入馬可夫模型以執行終身醫療成本效益分析。

    研究結果
    本研究篩選出130,957位主要分析族群，平均年齡為58.9歲，高血壓/高血脂盛行率為70.92%/58.62%，各用藥族群所占比率為SU組(93.5%)、Glinides組(2.5%)、thiazolidinediones (TZDs)組(2.3%)、acarbose組(1.7%)，至於查爾森共病指標(Charlson comorbidity index)，各用藥組患者於指標日期前相較於SU組而言並無顯著差異。而對於大血管事件發生率，SU組最高(17.0%)，依序為acarbose組(13.5%)、TZDs組(12.7%)、Glinides組(12.6%)，此外TZDs組中的rosiglitazone(12.2%)大血管事件發生率高於pioglitazone (10.4%)。而對於終身醫療成本效益分析，每減少一個大血管事件的發生，相較於SU組而言，使用acarbose 將多花新台幣1,682,602.0元；使用Glinides將少花新台幣268,592.5元；使用TZDs將多花新台幣1,298,820.7元。相較於rosiglitazone而言，使用pioglitazone將少花新台幣5,677,526.3元。單維敏感性分析(one-way sensitivity analysis)、機率性敏感性分析(probabilistic sensititivity analysis)亦得到一致的研究結果，惟Glinides組之醫療效益需至90歲以上族群方可顯現出來。

    研究結論
    研究結果顯示，相較於傳統使用之metformin合併SU類口服降血糖藥而言，使用metformin合併Glinides類口服降血糖藥對於預防大血管事件較具有經濟效益(dominated)，惟該效益需該患者使用至90歲以上時方可顯現出來，其餘處方類型則需權衡(trade-off)。而本研究亦發現相較於metformin合併rosiglitazone而言，使用metformin合併pioglitazone對於預防大血管事件較具有經濟效益(dominated)，且該效益在患者之每一年齡區間皆可觀察到。

    SUMMARY
    We analyzed metformin based add-on oral hypoglycemic agents to identify the regimen preventing macrovascular complications in a cost effective matter. Metformin-glinides were shown to be more cost effective as compared to conventional combination of metformin- sulfonylurea. And metformin-pioglitazone also showned cost effective as compared to met-rosiglitazone. Sensitivity analysis showned length of patients being treated and patient’s disease severity may influence the cost effectiveness of each metformin based dual therapy regimens.

    中文摘要 iii Extended abstract v 致謝 ix 第一篇 台灣糖尿病患者之二線口服降血糖藥對心血管病變之醫療成本效益分析 1 第一章 研究背景 1 第二章 文獻回顧 2 第一節 糖尿病簡介與其臨床處置 2 2.1.1 糖尿病定義與病徵 2 2.1.2 糖尿病流行病學 3 2.1.3 糖尿病臨床處置 4 第二節 糖尿病併發症 5 2.2.1 糖尿病併發症病徵 5 2.2.2 糖尿病併發症流行病學 7 2.2.3 糖尿病併發症醫療耗費 12 第三節 二線口服降血糖藥 16 2.3.1 二線口服降血糖藥之利用與耗費 16 2.3.2 二線口服降血糖藥預防糖尿病併發症之效益 21 2.3.3 二線口服降血糖藥之藥事經濟分析 29 第三章 研究目的 31 第一節 研究目的 31 第二節 研究假設 31 第四章 研究方法 32 第一節 研究設計 32 4.1.1 研究類型 32 4.1.2 研究材料及工具 32 4.1.3 納入條件 33 4.1.4 排除條件 34 4.1.5 研究流程 34 第二節 研究變項及操作定義 36 4.2.1 研究名詞及操作型定義 36 4.2.1 研究藥品成分定義 48 第三節 資料處理流程 49 第四節 統計分析 50 4.4.1 統計工具 50 4.4.2 統計模式設定 50 4.4.3 資料分析方法 50 第五章 研究結果 51 第一節 研究族群篩選流程 51 第二節 研究族群之臨床特性分布 53 5.2.1 總世代族群之臨床特性 53 5.2.2 二線口服降血糖用藥族群之臨床特性 54 第三節 二線口服降血糖用藥之醫療效益 58 5.3.1 大血管事件發生率及需治人數(NNT) 58 5.3.2 二線口服降血糖用藥族群之總死亡率 60 第四節 二線口服降血糖用藥之醫療花費 61 第五節 二線口服降血糖用藥之成本效益分析 65 第六節 敏感性分析 71 5.6.1 單維敏感性分析(one way sensitivity analysis) 71 5.6.2 機率性敏感性分析(Probabilistic Sensitivity Analyses) 72 第六章 研究討論 81 第一節 研究族群之臨床特性分布 81 第二節 二線口服降血糖用藥之醫療效益 84 6.2.1 二線口服降血糖用藥預防大血管事件之探討 84 6.2.2 二線口服降血糖用藥族群之總死亡率 89 第三節 二線口服降血糖用藥之醫療花費 91 第四節 二線口服降血糖用藥之成本效益分析 93 第五節 敏感性分析 98 6.5.1 單維敏感性分析(one way sensitivity analysis) 98 6.5.2 機率性敏感性分析(probabilistic sensitivity analysis) 99 第六節 研究限制 100 第七章 結論與建議 102 第八章 未來研究方向 103 第二篇 臨床藥事服務－評估二線口服降血糖藥品之服藥順從性差異 104 第一章 服務背景與目標 104 第二章 服務方法與材料 106 第一節 服務方法 106 2.1.1 服務對象 106 2.1.2 服務分組 106 2.1.3 服務地點 107 第二節 服務材料 107 第三章 服務結果 108 第一節 受試者基本資料 108 第二節 二線口服降血糖用藥患者之服藥順從性 109 第三節 二線口服降血糖用藥患者之正確用藥信仰 109 第四章 服務討論 112 第一節 受試者基本資料 112 第二節 二線口服降血糖用藥患者之服藥順從性 114 第三節 二線口服降血糖用藥患者之正確用藥信仰 119 第五章 服務結論與建議 120 參考文獻 122 表目錄 第一篇 台灣糖尿病患者之二線口服降血糖藥對心血管病變之醫療成本效益分析 表2-1 糖尿病人之中風盛行率 10 表2-2 糖尿病人之心血管疾病盛行率 11 表2-3　2000年~2009年糖尿病大、小血管併發症人數與比率 14 表2-4　2000年~2009年糖尿病大、小血管併發症年度醫療耗費點數 15 表2-5 2000~2009年OHAs開立比率 17 表2-6 口服降血糖藥品之每日耗用價格與許可證核發年份 19 表2-7 積極控制血糖對於糖尿病大、小血管併發症與死亡率之影響 24 表2-8 二線口服降血糖藥對於糖尿病併發症之實驗型研究結果(efficacy) 26 表2-9 二線口服降血糖藥對於糖尿病併發症之觀察型研究結果(effectiveness) 28 表2-10 二線口服降血糖藥之藥事經濟學分析 30 表4-1 本研究事件、共病症疾病全名與ICD-9-CM 2001年版國際疾病分類對照表 43 表4-2查爾森共病指標與ICD-9-CM 2001年版國際疾病分類對照表 44 表4-3糖尿病併發症嚴重度與ICD-9-CM 2001年版國際疾病分類對照表 45 表4-4 研究藥品成分列表 48 表5-1　總世代族群之臨床特性分布 53 表5-2　二線口服降血糖用藥族群之臨床特性分布 55 表5-3　大血管事件發生率及需治人數 (NNT) 59 表5-4　二線口服降血糖用藥族群之總死亡率 60 表5-5　大血管事件組於事件後第一年、第二年之總醫療花費(每人年) 64 表5-6　各用藥組死亡之總醫療花費(每人年) 64 表5-7　馬可夫鏈轉移機率 (Markov transition probabilities) 66 表5-8　各用藥組之差異成本效益比率 (Incremental cost effectiveness ratio, ICER ) 68 表5-9　Thiazolidinedione之差異成本效益比率 (Incremental cost effectiveness ratio, ICER ) 68 表5-10　單維敏感度分析(one way sensitivity analysis)-調整追蹤年齡區間 73 表5-11　單維敏感度分析(one way sensitivity analysis)-調整discount rate 75 表5-12　單維敏感度分析(one way sensitivity analysis)-調整患者疾病嚴重程度＊ 77 表5-12　單維敏感度分析(one way sensitivity analysis)-調整患者疾病嚴重程度(續)＊ 78 表5-13　機率性敏感度分析(Probabilistic Sensitivity Analyses)-加入醫療花費之分布(distribution) 79 表6-1　2000年至2009年糖尿病人死因分析 90 表6-2　本研究之藥事經濟效益分析與其他研究族群之比較 97 第二篇 臨床藥事服務－評估二線口服降血糖藥品之服藥順從性差異 表1-1影響第二型糖尿病人服藥順從性的因素 105 表3-1 受試者基本資料 108 表3-2　二線口服降血糖用藥患者之服藥順從性 110 表3-3　二線口服降血糖用藥患者之正確用藥信仰 111 表4-1 成大醫院現行之口服降血糖藥整理表 116 表4-2　成藥、指示藥、處方藥之衛教資訊 121 圖目錄 第一篇 台灣糖尿病患者之二線口服降血糖藥對心血管病變之醫療成本效益分析 圖2-1 第二型糖尿病階段式治療(stepped-care approach) 5 圖2-2 糖尿病大、小血管併發症 6 圖2-3 糖尿病併發症發生時間點 7 圖2-4 大、小血管併發症盛行率 8 圖2-5 1996~2002年引進之新藥理機轉二線口服降血糖藥 16 圖4-1 研究流程 35 圖5-1 研究族群篩選流程 52 圖5-2　觀測期間內之糖尿病相關醫療花費(每人年) 62 圖5-3　大血管事件模型 65 圖5-4　各用藥組用於預防大血管事件之差異成本效益圖　(Incremental cost effectiveness plane, ICEP ) 69 圖6-1低血糖造成心血管疾病可能的機轉 86 圖6-2　各用藥組用於預防大血管事件之差異成本效益圖-加入1~3倍人均GDP 95 第二篇 臨床藥事服務－評估二線口服降血糖藥品之服藥順從性差異 圖3-1 受試者教育程度 108

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