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| 研究生： |
魏辰芳 Wei, Chen-Fang |
|---|---|
| 論文名稱： |
非小細胞肺癌口服標靶治療藥物使用之臨床實證研究- 健保給付政策變更對藥物使用影響及藥物比較效果分析 Evidence Based Research on Tyrosine Kinase Inhibitors Use for Non-Small Cell Lung Cancer Treatment: Reimbursement Policy Assessment and Comparative Effectiveness Analysis |
| 指導教授： |
徐之昇
Hsu, Chih-Sheng |
| 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： | 2016 |
| 畢業學年度： | 104 |
| 語文別： | 中文 |
| 論文頁數： | 141 |
| 中文關鍵詞： | 非小細胞肺癌 、口服標靶藥物 、藥物使用趨勢 、給付規定變更之影響 、比較效果分析 |
| 外文關鍵詞： | Non-small cell lung cancer, Tyrosine Kinase Inhibitor, Drug utilization trend, Impact of policy change, Comparative effectiveness |
| 相關次數： | 點閱：132 下載：9 |
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研究背景
自1970年代開始，肺癌之發生率及死亡率不論在全球或在台灣皆有逐年上升的趨勢，且近十年國人十大惡性腫瘤死因當中，也以肺癌居冠。近九成肺癌病患為非小細胞肺癌患者，約七成在診斷時已為晚期，主要治療藥物包含化療及標靶藥物。全民健康保險自2004年起，對非小細胞肺癌的口服標靶藥物開放給付，並且逐步成為有EGFR基因突變者之第一線用藥。有鑒於癌症用藥的花費日漸升高，且目前國內以健保資料庫分析口服標靶藥物的藥物使用情形及治療效果之研究，仍然相當缺乏，因此有必要進行深入的分析及探討。本研究目的有三項：(1) 口服標靶藥物之每年藥物使用趨勢；(2) 健保給付規定之變更對於口服標靶藥物使用趨勢的影響；(3) 比較非小細胞肺癌晚期口服標靶藥物用於第二線之後的效果。
研究方法
本研究採回溯性研究設計，利用2004年至2013年（共10年）台灣全民健康保險資料庫資料（門診、住院醫令串明細檔），先擷取罹患肺癌之病患族群（利用重大傷病證明明細檔及門診、住院明細檔中國際疾病與死因分類代碼為162者），排除資料不全及小細胞肺癌患者後，得到非小細胞肺癌患者之就醫資料。接著，分析口服標靶藥物之藥物使用情形，藥物使用定義為處方人數比率及費用市場佔有率，再依據上述研究結果，利用中斷性時間序列分析法（Interrupted time series）進行健保給付規定影響之評估，其目的在於了解歷次健保於Gefitinib與Erlotinib放寬給付對其藥物使用造成的影響，是否可以增加藥物的可及性。此外，也利用Kaplan-Meier存活曲線及Cox比例風險模式，來比較Gefitinib與Erlotinib用於非小細胞肺癌晚期病患之後線治療效果，以整體存活期及無惡化存活期來評估。
研究結果
本研究於2004年至2013年共收錄92,220人診斷為非小細胞肺癌，十年之粗盛行率每十萬人口上升68人，粗發生率每十萬人口上升16人，粗死亡率則為每十萬人口上升9人，且男性之比例皆大於女性，以2013年來說，男性粗盛行率為每十萬人口138人，女性則為124人；男性年齡標準化發生率為每十萬人口29.7人，女性21.5人；男性年齡標準化死亡率為每十萬人口35.9人大於女性之24.3人。口服標靶藥物之10年藥物使用有逐年增加的趨勢，處方比率由2004年之4.52%上升至2013年之53.89%，費用市場佔有率則由2004年之3.85%上升至2013年之62.38%。在評估健保給付規定之影響中，2007年6月Erlotinib納入健保，造成Gefitinib處方比率減少20.69%，費用市場佔有率則減少6.59%；2007年11月Gefitinib變更為第二線用藥，造成Gefitinib處方比率上升54.32%，Erlotinib處方比率下降26.79%，費用市場佔有率則下降30.33%，口服標靶藥物整體處方比率上升15.58%；2008年6月Erlotinib變更為第二線用藥，使Gefitinib處方比率下降13.27%，Erlotinib處方比率上升22.62%，費用市場佔有率則上升21.66%，口服標靶藥物整體處方比率下降10.98%，整體費用市場佔有率則下降4.33%；2011年6月Gefitinib變更為第一線用藥時，造成Gefitinib處方比率上升21.76%，費用市場佔有率上升16.63%，Erlotinib處方比率下降10.30%，費用市場佔有率下降9.30%，口服標靶藥物整體處方比率上升6.31%。另外，隨著健保給付規定變更，新診斷之患者使用口服標靶藥物的時間自2004年平均802天，下降至2013年平均43天，非小細胞肺癌年齡標準化死亡率則是呈現波動狀態。比較Gefitinib與Erlotinib之臨床效果時，共分析4,130人，可以發現Gefitinib之整體存活期平均為11.90 ± 10.09個月，中位數約為10個月，Erlotinib平均為12.43 ± 10.59個月，中位數則為9個月（已校正之風險比為1.014，P=0.7017）；而Gefitinib之無惡化存活期平均為8.47 ± 8.54個月，中位數為6個月，Erlotinib平均為8.70± 8.57個月，中位數亦為6個月（已校正之風險比為1.022，P=0.5232），因此Gefitinib於臨床效果上與Erlotinib相似。
研究結論
本研究發現，非小細胞肺癌之口服標靶藥物處方比率、費用市場佔有率及病患平均費用皆有逐年上升之趨勢，且前兩者在2013年已超過60%。在健保給付規定變更之影響評估中，發現大部分健保給付規定變更對於口服標靶藥物的使用皆有顯著的影響，若口服標靶藥物給付規定放寬，則可能造成其本身處方比率、費用市場佔有率顯著上升，放寬的藥物其可及性增加，但也使另一口服標靶藥物相對下降，而若有新的口服標靶藥物納入市場，亦使既有的口服標靶藥物處方比率、費用市場佔有率下降。另外，比較Gefitinib與Erlotinib於非小細胞肺癌晚期用於後線之整體存活期及無惡化存活期的結果發現，Gefitinib之臨床表現和Erlotinib相似。
SUMMARY
Non-small cell lung cancer was the major type of lung cancer, which was the leading cause of cancer mortality. Since the high-price oral targeted therapies were launched, the burden of National Health Insurance was expected to increase. The first aim of this study was to evaluate oral targeted therapies’ use and the impact of changes of reimbursement policy on use. We found that oral targeted therapies truly dominated the prescribing rate and the expenditure of treating non-small cell lung cancer. There were some impacts on the use of oral targeted therapies caused by changes of reimbursement policy as our expectation. Also, to our knowledge, there was lack of comparative effectiveness studies between gefitinib and erlotinib. We compared their clinical outcomes directly and found that gefitinib might have similar overall survival and progression-free survival as erlotinib.
INTRODUCTION
Lung cancer is one of the most commonly diagnosed cancers as well as the leading cause of cancer deaths in Taiwan. About 85% of all lung cancers are identified as non-small cell, and approximately 75% of these are metastatic or advanced at diagnosis. Since 2004, oral targeted therapies for non-small cell lung cancer had been launched into the market and gradually became first-line treatment for EGFR mutation patients. The healthcare expenditure may be affected by the high price of oral targeted therapies. However, there was no sufficient information about the use of oral targeted therapies in Taiwan and the impact of the reimbursement policy change. Besides, rare studies were conducted to compare the effectiveness between gefitinib and erlotinib. Thus, this study aimed to evaluate drug utilization trend, impact of policy change on oral targeted therapies’ use and compare the effectiveness between oral targeted therapies for non-small cell lung cancer.
MATERIALS AND METHODS
A retrospective study design was applied to analyze the drug utilization trend, impact of reimbursement policy change and comparative effectiveness analysis between gefitinib and erlotinib for non-small cell lung cancer. This study mainly used nationwide claims data from Taiwan’s National Health Insurance Research Database (NHIRD), which covers a wide range of prescription medicines, inpatient and outpatient medical services. The non-small cell lung cancer related prescriptions was identified by International Classification of Diseases, 9th edition (ICD-9) diagnosis codes for cancer (codes: 162) and excluded patients with small cell lung cancer. All yearly and monthly claims data related to patients with non-small cell lung cancer, including details of prescription and insurer spending, for antineoplastic agents between 2004 and 2013 were retrieved from NHIRD. We used interrupted time series to evaluate the impact of the reimbursement policy change. Besides, we compared the overall survival and progression-free survival between gefitinib and erlotinib for the metastatic stage treatment by using Kaplan-Meier Curves and Cox proportional hazards model.
RESULTS AND DISCUSSION
To analyze the drug utilization trend, the present study included 92,220 patients with non-small cell lung cancer from 2004 to 2013. We first described the epidemiology of non-small cell lung cancer in Taiwan. In the ten-year-period, we analyzed the prevalence rate, incidence rate and mortality rate, which had a growth rate by 68, 16 and 9 patients per 100,000 populations, respectively. Most patients were male. Then, the yearly trend of oral targeted therapies’ use was increasing as well. The prescribing rate of oral targeted therapies was around 5% in 2004 and went up to 54%, while the market share by cost risen from nearly 4% to 62%. Both prescribing rate and market share by cost were growing rapidly. To our expectation, the change of the reimbursement policy would affect the use of both gefitinib and erlotinib significantly. The first change is that erlotinib was launched into the market in June, 2007. It reduced the prescribing rate of gefitinib by 20.69% and its market share by cost had a 6.59% decrease. The second change is that gefitinib turned to second-line treatment in November, 2007, which caused 54.32% increase of gefitinib’s prescribing rate, 26.79% decrease of erlotinib’s prescribing rate and 30.33% decrease of erlotinib’s market share by cost. The third change is that erlotinib turned to second-line treatment in June, 2008. It lead to a decrease of gefitinib’s prescribing rate by 13.27% and as for erlotinib, the policy increased 22.62% of erlotinib’s prescribing rate and 21.66% of erlotinib’s market share by cost. The last change is that gefitinib became first-line treatment in June, 2011, which lead to a 21.76% and 16.63% growth on gefitinib’s prescribing rate and market share by cost, respectively. Erlotinib had a 10.30% and 9.30% decrease on prescribing rate and market share by cost as well. In the last part of the study, which compares the effectiveness between gefitinib and erlotinib, we found that gefitinib’s median overall survival was 10 months (Mean± SD: 11.90 ± 10.09) and erlotinib’s median overall survival was 9 months (Mean± SD: 12.43 ± 10.59). As for median progression-free survival, gefitinib was 6 months (Mean± SD: 8.47 ± 8.54) and erlotinib was 6 months (Mean± SD: 8.70 ± 8.57). Gefitinib had similar clinical effects as erlotinib.
CONCLUSION
The present study had three main findings. First of all, oral targeted therapies’ use was increasing gradually by year since they were launched and now dominate the prescribing rate and expenditure of non-small cell lung cancer. Second, the changes of the reimbursement policy had the significant impact on the use of oral targeted therapies. We also found that gefitinib might have similar outcomes on survival when compared with erlotinib, which indicated that both gefitinib and erlotinib are good choice for treatment.
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