臺灣博碩士論文加值系統

背景：慢性B型肝炎在台灣盛行率高，估計患者約300萬人左右，可能導致嚴重疾病如肝硬化及肝癌，造成社會重大損失。中央健康保險局自97年8月1日起將貝樂克（Entecavir）加入健保給付，和台灣過去用藥干安能（Lamivudine)、長短效型干擾素等一併成為第一線用藥，對於醫界、民眾以及健保財務將產生衝擊。本研究擬針對慢性B型肝炎e抗原陰性病患為對象，將Entecavir與傳統用藥Lamivudine進行比較，進行成本效果分析（Cost-Effectiveness Analysis, CEA），瞭解藥物長期治療後所花費的成本以及其臨床療效，作為政策參考之用。

方法：本研究為一成本效果研究，採健保局觀點，比較慢性B型肝炎e抗原陰性病患使用兩種不同藥物的結果。Entecavir 0.5mg，以Lamivudine 100mg作為對照組，兩者最長給付三年，若復發則再給予一循環治療；並使用Adefovir作為Lamivudine產生抗藥性後之救援藥物，最長使用兩年。為模擬慢性B型肝炎e抗原陰性的疾病進展及各項成本使用，建構一馬可夫模式呈現疾病轉移狀態；模式假設一群40歲符合治療條件的病患進入治療模式，並觀察終身（60）年，以計算推估其終身成本與效果。本研究之折現率採3％，並進行單維及機率性敏感度分析。

結果：模式模擬結果顯示，Entecavir組平均每人終身成本為NT 546,507、Lamivudine組平均每人終身成本為NT 510,095，相差36,412元；前者之增加品質校正生活年（QALYs）為13.3913年，後者增加品質校正生活年（QALYs）為13.0448年，相差0.3465年。而將兩組成本差除以效果差，即為遞增成本效果比值（ICER）值，在此研究中表示增加一份QALY需增加的成本，為NT 105,104。機率性敏感度分析結果，ICER值為NT 143,210。

結論：台灣目前尚未對遞增成本效果比值之閾值有所共識，故需引用國外之標準。本研究以台灣及美國2008年之GNP比率乘以美國標準閾值 50,000美元，得到美元18,621元，折合新台幣約610,120元per QALY，以此做為基準閾值。本研究在3％折現下ICER值為NT 105,104 per QALY，低於設定之標準閾值 NT 610,120，故稱使用Entecavir之治療策略具有成本效果。經由機率性敏感度分析以及各種不同折現率之計算，ICER值依然小於標準閾值，結果相同。
在單維敏感度分析中，可瞭解藥物本身之療效及成本是影響模式ICER值最大之參數，建議相似研究可針對這些參數加強探討，亦可從不同觀點來計算成本，以獲得更完整以及更宏觀的研究結果，供政策制訂者參考。

Background:
Chronic hepatitis B (CHB) has high prevalence in Taiwan.
Around 3 million people are infected and suffered from severe diseases like Compensated Cirrhosis and Hepatocellular Carcinoma, causing great damage to the society.

The Bureau of National Health Insurance (BNHI) has included Entecavir into a part of medical treatment coverage since August 1, 2008.This adjustment enabled Entecavir alone with Lamivudine and interferon-α to be the first line medication, and made a great impact on Medical profession, general public and BNHI's Financial Status.

This reserch was aimed at HBeAg-negative CHB patients. By comparing the cost and clinical effect under long-term treatment of Entecavir and Traditional Lamivudine, and constructing a cost-effectiveness analysis, this research could provide reference for future insurance policy.


Method:
A cost-effectiveness analysis was conducted from BNHI's perspective to compare the results of HBeAg-negative CHB patients using two different drugs.
The Experimental Group was Entecavir 0.5mg, and Lamivudine 100mg was the Control Group. Both were treated no more than three years. If virus develop resistance, patients would be treated for another cycle. Adefovir would be used as the salvage medicine when resistance occurs, medication up to two years.

The Markov model was constructed to simulate chronic hepatitis B disease progression and potentially incurred costs among a cohort of patients.
A time frame of 60 years was chosen to model the lifetime outcomes of a hypothetical cohort comprising 40-year-old CHB patients. In the base-case analysis, a 3% discount rate was used to discount future costs and effectiveness. Simple sensitivity analysis and probabilistic sensitivity analysis were done for every parameter used in the model.





Results:
In the base-case analysis, for a cohort of 40-year-old CHB patients, the average cost per person in Entecavir group was NT$ 546,507, the Lamivudine group was nt 510,095, the difference was NT$ 36,412; The former showed Quality-adjusted life years (QALYs) of 13.3913, the latter was 13.0448 QALYs, the difference was 0.3465 QALY.

Divide the difference in cost by the difference in effectiveness equals incremental cost-effectiveness ratio (ICER). The ICER in this research was estimated to be NT$ 105,104 per QALY. The probabilistic sensitivity analysis showed ICER to be NT$ 143,210 per QALY.


Conclusion:
There's still no consensus on the standard threshold of incremental cost-effectiveness in Taiwan, consequently it's necessary to cite the standards from other countries. The calculation is to multiply the GNP ratio of Taiwan and United States in year 2008 by U.S. standard threshold of USD $50,000. The product was USD $ 18,621, equivalent to NT$ 610,120 per QALY, thus was used as standard threshold in this research.

Under the 3% discount rate, the ICER was NT$ 105,104 per QALY, and was lower than the standard threshold of NT$ 610,120 per QALY, therefore it could be concluded that the Entecavir treatment strategy was cost-effective. Through probabilistic sensitivity analysis and other different discount calculations, the ICER value was still smaller than standard threshold, as a result, the same conclusion could be conducted.

In simple-sensitivity analysis, it was realized that the effectiveness of treatments and costs were the most contributing factors to ICER value. So it is suggested that in the future, researchers can focus on examining these factors, or calculate costs from different perspective to obtain more complete and extensive results for policy makers.

致謝 i
中文摘要 ii
Abstract iv
目錄 vi
圖目錄 vii
表目錄 viii
第壹章 緒論 1
第一節 研究背景與動機 1
第二節 研究目的 3
第貳章 文獻探討 4
第一節 B型肝炎之簡介 4
第二節 B型肝炎臨床治療藥物 8
第三節 經濟評估 11
第四節 國內外相關文獻探討 18
第參章 研究設計與方法 26
第一節 研究架構 26
第二節 參數來源與變項定義 38
第三節 研究假設 52
第肆章 研究結果 60
第一節 成本效果分析之結果 60
第二節 敏感度分析 66
第伍章 討論 74
第一節 重要結果討論 74
第二節 研究限制 77
第陸章 結論 79
參考文獻 80

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