跳到主要內容

臺灣博碩士論文加值系統

(44.211.31.134) 您好!臺灣時間:2024/07/24 16:30
字體大小: 字級放大   字級縮小   預設字形  
回查詢結果 :::

詳目顯示

我願授權國圖
: 
twitterline
研究生:陳浩銘
研究生(外文):Hao-Ming Chen
論文名稱:慢性阻塞性肺病於三合一藥物療法之臨床效果及藥物經濟學研究
論文名稱(外文):Effectiveness and pharmacoeconomics of triple harmacotherapy for chronic obstructive pulmonary disease
指導教授:蔡東榮蔡東榮引用關係
指導教授(外文):Tong-Rong Tsai
學位類別:碩士
校院名稱:高雄醫學大學
系所名稱:臨床藥學研究所
學門:醫藥衛生學門
學類:藥學學類
論文種類:學術論文
論文出版年:2013
畢業學年度:101
語文別:中文
論文頁數:140
中文關鍵詞:慢性阻塞性肺病三合一藥物療法全民健康保險研究資料庫成本效果
外文關鍵詞:chronic obstructive pulmonary diseasetriple combine pharmacotherapynational health insurance research databasecost-effectiveness
相關次數:
  • 被引用被引用:0
  • 點閱點閱:529
  • 評分評分:
  • 下載下載:0
  • 收藏至我的研究室書目清單書目收藏:1
研究背景:慢性阻塞性肺病(COPD)為一不完全可逆之呼吸道發炎及肺部實質化損傷疾病,其可造成呼吸流量之限制,影響生活品質,最後可能併發心肺相關疾病而導致死亡。根據世界衛生組織(WHO)統計,2004年全世界約有六千四百萬人口罹患COPD,更大膽估計於2030年時,COPD將成為世界第三大死亡原因之疾病。依據全球阻塞性肺病倡議組織(GLOD)所發表的治療指引中,嚴重COPD患者可選擇使用三合一藥物療法,即長效型抗膽鹼製劑(LAMA)加上長效型乙型交感神經致效劑合併吸入型類固醇(LABA/ICS),但此組合療法單次藥費近三千元新台幣,對於醫療成本支出為一種大負荷;於臨床效果方面,對於何種LABA/ICS為三合一藥物療法之選擇,尚無明確答案。
研究目的:本研究所探討之LAMA為Tiotropium (簡稱Tio),而LABA/ICS有Salmeterol/Fluticasone Combination (簡稱SFC)及Budesonide/Formoterol Combination (簡稱BFC),上述LAMA及LABA皆可用於COPD之控制,而根據2013年台灣健保給付價格訂定,BFC比SFC便宜176元新台幣;根據文獻回顧,發現Tio + BFC之臨床效果可能較佳,但證據結果尚未充足。故希望透過本研究,確認究竟何種三合一藥物療法,能有較佳的臨床效果及其經濟效益。
研究方法:本研究將利用國家衛生研究院所提供之2000年全民健保資料百萬人承保抽樣檔進行研究分析,以SAS作為資料擷取及運算工具,研究期間為2005年01月01日至2009年12月31日,依照定義的納入及排除條件,篩選出2006年01月01日至2008年12月31日之病患族群,每位病患最長追蹤時間為一年,經計算及分析後,得兩組三合一藥物療法之每年疾病惡化機率及其平均單次直接醫療成本,再將所獲得之參數帶入已認證過之馬可夫模型,模擬五年後的遞增成本效果比值(ICER)。
研究結果:本研究經納入及排除條件,初步篩選出Tio + SFC組有131人,Tio + BFC組有73人。Tio + SFC組之每年非急性惡發生機率為0.1715,Tio + BFC組為0.2765;於急性惡化發生機率方面,Tio + SFC組每年發生機率為0.0402,Tio + BFC組為0.0932。穩定控制之Tio + SFC組之平均單次醫療成本為4,869.77元新台幣,Tio + BFC組為4,546.74元新台幣;於非急性惡化平均單次醫療成本,Tio + SFC組為3,931.68元新台幣,Tio + BFC組為3,055.51元新台幣;於急性惡化平均單次醫療成本,Tio + SFC組為41,812.84元新台幣,Tio + BFC組為27,661.07元新台幣。將上述參數結合其他研究者已發表之臨床效益(utility)測量值,放入馬可夫模型模擬,得平均遞增成本效果比為-4,074.88元/完整健康品質生活年。經單變項敏感度測試,改變效益值、疾病惡化機率或直接醫療成本,其成本效果比值皆為負值;經多變項之情境分析測試,於最佳疾病惡化控制狀況、最低可能直接成本及較佳之臨床效益值之情境,得成本效果比值為-8,318.72元/完整健康品質生活年。
研究結論:經初步計算,Tio + SFC之組合,雖單次醫療成本較高,但因具有較佳的臨床效果(effectiveness),且能顯著降低病患進入急診之次數,以馬可夫模型模擬後,得到的成本效果比值為負值,顯示其組合為一優勢策略(dominant strategy)。因此,若考量長遠的病患生活品質及醫療資源耗用,Tio + SFC可能為較佳的藥物經濟學選擇。


Background: Chronic obstructive pulmonary disease (COPD) is not fully reversible disease of airway inflammation and lung parenchyma, that can development of airflow limitation, and also decrease the quality of life, finally, maybe cause comorbidity of cardiopulmonary-related disease, and lead to death. According to World Health Organization (WHO) estimates, 64 million people have COPD in 2004, WHO fiercely predicts that COPD will become the third leading cause of death worldwide by 2030. Base on The Global Initiative for Chronic Obstructive Lung Disease (GOLD) reported guidance of management and treatment, severe stage of COPD patient can use the triple combine therapy, it means that long-acting muscarinic antagonist (LAMA) plus long acting beta agonist combine with inhaled corticosteroid (LABA/ICS), but these pre cost of combine therapy almost approaching three thousands, and the guidance do not answer that which LABA/ICS is better for choice.
Aims: The drug of this study, the LAMA is tiotropium (abbreviated Tio), the LABA/ICS have two item, one of this is salmeterol/fluticasone combination (abbreviated SFC), another is budesonide/formoterol combination (abbreviated BFC), both combination can use to control COPD. According to reimbursement of Bureau of National Health Insurance, Department of Health, Taiwan, the BFC is cheaper than SFC 176 NTD, but review some academic article reveal that Tio + SFC maybe have the better clinical outcome. So, the prospect of this study is Tio + SFC, which triple combine pharmacotherapy, have the best choice of clinical and economic outcome.
Methods: This study use Longitudinal Health Insurance Database 2000 (LHID2000) that provided by the National Health Research Institutes, Taiwan, and capture data and cumulate value by SAS. The study period is 2005 to 2009, and the enrollment period is 2006 to 2008, based on the definition of inclusion criteria and exclusion criteria to filter the eligible participants, every participant follow up one year, and cumulate the per exacerbation rate and per cost each event happened on two triple therapy group, and then put the parameter that capture by above description to the Markov model which is valid by other study, the time horizon is five years, calculate the incremental cost-effectiveness ratio (ICER).

Results: Firstly, the original data through the inclusion and exclusion criteria, Tio + SFC group have 131 persons, Tio + BFC group have 73 persons. Secondarily, the incident rate of non-severe exacerbation in Tio + SFC group is 0.1715, and Tio + BFC group is 0.2765. The incident rate of severe exacerbation per month in Tio + BFC group is 0.0402, and Tio + BFC group is 0.0932. Third, the mean cost of stable control per Tio + SFC group is 4,869.77 NTD, and the Tio + BFC group is 4,546.74 NTD. The mean cost of non-severe exacerbation per time in Tio + SFC group is 3,931.68 NTD, and Tio + BFC group is 3,055.51 NTD. The mean cost of severe exacerbation in Tio + SFC group is 41,812.84 NTD, and Tio + BFC group is 27,661.07 NTD. Finally, combine the above parameter with the utility value from other study, input these parameter to the Markov model, simulate the five years outcome, the incremental cost effectiveness is -4,074.88 NTD/complete health year.
Conclusion: Through the above calculation, although Tio + SFC have higher medical expenditure, but this combination pharmacotherapy can provide better utility, and decrease the frequency of emergency room visit. So that, if consider patient’s quality of life and the medical resource use for long-term, Tio + SFC maybe the dominant strategy.


中文摘要 I
英文摘要 IV
圖目錄 XII
附件目錄 XIV
專有名詞縮寫對照表 XV
第壹章 前言 1
第一節 研究背景 1
第二節 研究動機 3
第三節 研究目的 4
第四節 研究重要性 5
第貳章 疾病暨治療管理 6
第一節 慢性阻塞性肺病之簡介 6
一. 流行病學 6
二. 病因學 7
三. 病態生理學 9
四. 急性惡化之病態生理學 12
五. 臨床表徵 13
六. 族群分類 14
第二節 慢性阻塞性肺病的治療 17
一. 治療目標 17
二. 非藥物治療 18
三. 藥物治療 19
四. 治療指引 20
第參章 三合一療法之實證 23
第一節 臨床效果 25
第二節 藥物經濟學 29
第肆章 研究材料與方法 31
第一節 研究材料 31
一. 資料來源 31
二. 藥品成本資料 35
三. 成本效果評估-馬可夫模型 36
四. 應用軟體 38
第二節 研究對象及追蹤時間 39
第三節 研究模式架構 44
第四節 研究變項及定義 48
第五節 資料處理 50
第六節 統計分析方法 57
一. 研究假設 57
二. 分析方法 59
第伍章 研究結果 61
第一節 目標族群之擷取與各基礎值 61
第二節 疾病控制及其參數 69
第三節 疾病成本參數 79
第四節 成本效果分析 81
第五節 敏感度分析 84
一. 單變項敏感度分析 85
二. 情境式敏感度分析 87
第陸章 討論 89
第一節 重要結果討論 89
第二節 研究限制 93
第三節 未來發展 94
第柒章 結論與建議 95
第一節 研究結論 95
第二節 建議 96
參考文獻 97
附件 102


1.Chronic respiratory diseases: Chronic obstructive pulmonary disease (COPD) World Health Organization. (Accessed April 14, 2013 at http://www.who.int/respiratory/copd/en/.)
2.Global strategy for the diagnosis, management, and prevention of chronic obstructive pulmonary disease The Global Initiative for Chronic Obstructive Lung Disease, 2011. (Accessed April 14, 2013, at http://www.goldcopd.org/Guidelines/guidelines-resources.html.)
3.Chronic Obstructive Pulmonary Disease - Guidance of Diagnosis and Treatment 2012. (Accessed April 14, 2013, at http://www.tspccm.org.tw/.)
4.Chiang CH. Cost analysis of chronic obstructive pulmonary disease in a tertiary care setting in Taiwan. Respirology 2008;13:689-94.
5.Baloira A. [Triple therapy in chronic obstructive pulmonary disease]. Arch Bronconeumol 2010;46 Suppl 8:25-30.
6.Ait-Khaled N, Enarson DA, Ottmani S, El Sony A, Eltigani M, Sepulveda R. Chronic airflow limitation in developing countries: burden and priorities. Int J Chron Obstruct Pulmon Dis 2007;2:141-50.
7.Raherison C, Girodet PO. Epidemiology of COPD. Eur Respir Rev 2009;18:213-21.
8.Peabody JW, Schau B, Lopez-Vidriero M, Vestbo J, Wade S, Iqbal A. COPD: a prevalence estimation model. Respirology 2005;10:594-602.
9.Miravitlles M, Sobradillo V, Villasante C, et al. [Epidemiological study of chronic obstructive pulmonary disease in Spain (IBERPOC): recruitment and field work]. Arch Bronconeumol 1999;35:152-8.
10.Miravitlles M, Andreu I, Romero Y, Sitjar S, Altes A, Anton E. Difficulties in differential diagnosis of COPD and asthma in primary care. Br J Gen Pract 2012;62:e68-75.
11.Damage of smoking - Respiratory system. Bureau of Health Promotion, Department of Health, R.O.C. (Taiwan), 2009. (Accessed April 14, 2013, at http://tobacco.bhp.doh.gov.tw/Show.aspx?MenuId=178.)
12.Tan WC, Seale P, Ip M, et al. Trends in COPD mortality and hospitalizations in countries and regions of Asia-Pacific. Respirology 2009;14:90-7.
13.Groneberg DA, Chung KF. Models of chronic obstructive pulmonary disease. Respir Res 2004;5:18.
14.Tatsumi K. [Effects of smoking on the pathogenesis of COPD]. Nihon Rinsho 2007;65:605-10.
15.Laniado-Laborin R. Smoking and chronic obstructive pulmonary disease (COPD). Parallel epidemics of the 21 century. Int J Environ Res Public Health 2009;6:209-24.
16.Tam A, Sin DD. Pathobiologic mechanisms of chronic obstructive pulmonary disease. Med Clin North Am 2012;96:681-98.
17.Elisabetta Rosi GS. Cigarette Smoking and Dyspnea Perception. TOBACCO INDUCED DISEASES 2004;Vol. 2,:35-42.
18.Garcia-Aymerich J, Tobias A, Anto JM, Sunyer J. Air pollution and mortality in a cohort of patients with chronic obstructive pulmonary disease: a time series analysis. J Epidemiol Community Health 2000;54:73-4.
19.Cohen BH, Ball WC, Jr., Brashears S, et al. Risk factors in chronic obstructive pulmonary disease (COPD). Am J Epidemiol 1977;105:223-32.
20.Govender N, Lalloo UG, Naidoo RN. Occupational exposures and chronic obstructive pulmonary disease: a hospital based case-control study. Thorax 2011;66:597-601.
21.Corhay JL, Frusch N, Louis R. [COPD: genetics and environmental interactions]. Rev Med Liege 2012;67:292-7.
22.Mulgrew AT, Taggart CC, McElvaney NG. Alpha-1-antitrypsin deficiency: current concepts. Lung 2007;185:191-201.
23.Barnes PJ. Chronic obstructive pulmonary disease. N Engl J Med 2000;343:269-80.
24.Stockley RA. Neutrophils and the pathogenesis of COPD. Chest 2002;121:151S-5S.
25.Hogg JC. Pathophysiology of airflow limitation in chronic obstructive pulmonary disease. Lancet 2004;364:709-21.
26.Macnee W. Pathogenesis of chronic obstructive pulmonary disease. Clin Chest Med 2007;28:479-513, v.
27.Emphysema — A Disease of Small Airways or Lung Parenchyma? , 2011. (Accessed April. 29, 2013, at http://inspiro-bg.com/emphysema-v-a-disease-of-small-airways-or-lung-parenchyma/.)
28.Sethi S. Infectious etiology of acute exacerbations of chronic bronchitis. Chest 2000;117:380S-5S.
29.Sethi S, Murphy TF. Bacterial infection in chronic obstructive pulmonary disease in 2000: a state-of-the-art review. Clin Microbiol Rev 2001;14:336-63.
30.Palm KH, Decker WW. Acute exacerbations of chronic obstructive pulmonary disease. Emerg Med Clin North Am 2003;21:331-52, viii.
31.Pleasants RA. Review of guidelines and the literature in the treatment of acute bronchospasm in chronic obstructive pulmonary disease. Pharmacotherapy 2006;26:156S-63S.
32.Quon BS, Gan WQ, Sin DD. Contemporary management of acute exacerbations of COPD: a systematic review and metaanalysis. Chest 2008;133:756-66.
33.Lightowler JV, Wedzicha JA, Elliott MW, Ram FS. Non-invasive positive pressure ventilation to treat respiratory failure resulting from exacerbations of chronic obstructive pulmonary disease: Cochrane systematic review and meta-analysis. BMJ 2003;326:185.
34.Vollenweider DJ, Jarrett H, Steurer-Stey CA, Garcia-Aymerich J, Puhan MA. Antibiotics for exacerbations of chronic obstructive pulmonary disease. Cochrane Database Syst Rev 2012;12:CD010257.
35.Soler N, Torres A. Significance of sputum purulence to guide antibiotic therapy in exacerbations of COPD. Eur Respir J 2013;41:248-9.
36.Lee JS, Park DA, Hong Y, et al. Systematic review and meta-analysis of prophylactic antibiotics in COPD and/or chronic bronchitis. Int J Tuberc Lung Dis 2013;17:153-62.
37.Boggon R, Hubbard R, Smeeth L, et al. Variability of antibiotic prescribing in patients with chronic obstructive pulmonary disease exacerbations: a cohort study. BMC Pulm Med 2013;13:32.
38.Perng DW, Wu CC, Su KC, Lee YC, Perng RP, Tao CW. Additive benefits of tiotropium in COPD patients treated with long-acting beta agonists and corticosteroids. Respirology 2006;11:598-602.
39.Aaron SD, Vandemheen KL, Fergusson D, et al. Tiotropium in combination with placebo, salmeterol, or fluticasone-salmeterol for treatment of chronic obstructive pulmonary disease: a randomized trial. Ann Intern Med 2007;146:545-55.
40.Singh D, Brooks J, Hagan G, Cahn A, O''Connor BJ. Superiority of "triple" therapy with salmeterol/fluticasone propionate and tiotropium bromide versus individual components in moderate to severe COPD. Thorax 2008;63:592-8.
41.Cazzola M, Ando F, Santus P, et al. A pilot study to assess the effects of combining fluticasone propionate/salmeterol and tiotropium on the airflow obstruction of patients with severe-to-very severe COPD. Pulm Pharmacol Ther 2007;20:556-61.
42.Welte T, Miravitlles M, Hernandez P, et al. Efficacy and tolerability of budesonide/formoterol added to tiotropium in patients with chronic obstructive pulmonary disease. Am J Respir Crit Care Med 2009;180:741-50.
43.Najafzadeh M, Marra CA, Sadatsafavi M, et al. Cost effectiveness of therapy with combinations of long acting bronchodilators and inhaled steroids for treatment of COPD. Thorax 2008;63:962-7.
44.Mittmann N, Hernandez P, Mellstrom C, Brannman L, Welte T. Cost effectiveness of budesonide/formoterol added to tiotropium bromide versus placebo added to tiotropium bromide in patients with chronic obstructive pulmonary disease: Australian, Canadian and Swedish healthcare perspectives. Pharmacoeconomics 2011;29:403-14.
45.National Health Insurance Research Database. National Health Research Institutes, 2013. (Accessed April, 14, 2013, at http://nhird.nhri.org.tw/date_cohort.htm#2.)
46.Chatterjee A, Shah M, D''Souza AO, Bechtel B, Crater G, Dalal AA. Observational study on the impact of initiating tiotropium alone versus tiotropium with fluticasone propionate/salmeterol combination therapy on outcomes and costs in chronic obstructive pulmonary disease. Respir Res 2012;13:15.
47.Oostenbrink JB, Rutten-van Molken MP, Monz BU, FitzGerald JM. Probabilistic Markov model to assess the cost-effectiveness of bronchodilator therapy in COPD patients in different countries. Value Health 2005;8:32-46.
48.Kuo LC, Yang PC, Kuo SH. Trends in the mortality of chronic obstructive pulmonary disease in Taiwan, 1981-2002. J Formos Med Assoc 2005;104:89-93.
49.McGraw-Hill. CURRENT Medical Diagnosis & Treatment Online. In: Chapter 9 Pulmonary Disorders: Stephen J. McPhee; 2013.
50.Tzortzaki EG, Proklou A, Siafakas NM. Asthma in the Elderly: Can We Distinguish It from COPD? J Allergy (Cairo) 2011;2011:843543.
51.Buffels J, Degryse J, Liistro G, Decramer M. Differential diagnosis in a primary care population with presumed airway obstruction: a real-life study. Respiration 2012;84:44-54.
52.Wang Z, Xiong YX. Lung sound patterns help to distinguish congestive heart failure, chronic obstructive pulmonary disease, and asthma exacerbations. Acad Emerg Med 2012;19:79-84.
53.Cao Y, Gong W, Zhang H, et al. A Comparison of Serum and Sputum Inflammatory Mediator Profiles in Patients with Asthma and COPD. J Int Med Res 2012;40:2231-42.
54.Vukoja M, Rebic P, Lazic Z, et al. Early detection of asthma and chronic obstructive pulmonary disease in primary care patients. Med Pregl 2013;66:46-52.
55.Kojima S, Sakakibara H, Motani S, et al. Effects of smoking and age on chronic obstructive pulmonary disease in Japan. J Epidemiol 2005;15:113-7.
56.Keam SJ, Keating GM. Tiotropium bromide. A review of its use as maintenance therapy in patients with COPD. Treat Respir Med 2004;3:247-68.
57.Kharidia J, Fogarty CM, Laforce CF, et al. A pharmacokinetic/pharmacodynamic study comparing arformoterol tartrate inhalation solution and racemic formoterol dry powder inhaler in subjects with chronic obstructive pulmonary disease. Pulm Pharmacol Ther 2008;21:657-62.
58.Dalby C, Polanowski T, Larsson T, Borgstrom L, Edsbacker S, Harrison TW. The bioavailability and airway clearance of the steroid component of budesonide/formoterol and salmeterol/fluticasone after inhaled administration in patients with COPD and healthy subjects: a randomized controlled trial. Respir Res 2009;10:104.
59.Singh SD, Whale C, Houghton N, Daley-Yates P, Kirby SM, Woodcock AA. Pharmacokinetics and systemic effects of inhaled fluticasone propionate in chronic obstructive pulmonary disease. Br J Clin Pharmacol 2003;55:375-81.
60.Charlson ME, Pompei P, Ales KL, MacKenzie CR. A new method of classifying prognostic comorbidity in longitudinal studies: development and validation. J Chronic Dis 1987;40:373-83.
61.Deyo RA, Cherkin DC, Ciol MA. Adapting a clinical comorbidity index for use with ICD-9-CM administrative databases. J Clin Epidemiol 1992;45:613-9.
62.Welte T. Optimising treatment for COPD--new strategies for combination therapy. Int J Clin Pract 2009;63:1136-49.
63.Tashkin DP, Ferguson GT. Combination bronchodilator therapy in the management of chronic obstructive pulmonary disease. Respir Res 2013;14:49.
64.Blais L, Forget A, Ramachandran S. Relative effectiveness of budesonide/formoterol and fluticasone propionate/salmeterol in a 1-year, population-based, matched cohort study of patients with chronic obstructive pulmonary disease (COPD): Effect on COPD-related exacerbations, emergency department visits and hospitalizations, medication utilization, and treatment adherence. Clin Ther 2010;32:1320-8.
65.Research TSfPaO. Guidelines of Methodological Standards for Pharmacoeconomic Evaluations. In; 2006.
66.Pulmonary Disease, Chronic Obstructive - Definition of COPD. CURRENT Medical Diagnosis & Treatment 2013, 2013. (Accessed 2013, at http://www.haz-map.com/copd.htm.)


QRCODE
 
 
 
 
 
                                                                                                                                                                                                                                                                                                                                                                                                               
第一頁 上一頁 下一頁 最後一頁 top