使用gefitinib或化學治療對末期非小細胞肺癌病患的醫療費用及成本效果分析

Management Costs and Cost Effectiveness Analysis of Gefitinib or Combination Chemotherapy in Patients with Stage IIIB or IV Non-Small Cell Lung Cancer

施維宜(Wei-Yi Shih)

指導教授 ： 楊志新

國立臺灣大學/醫學院/臨床藥學研究所/碩士(2008年)

https://doi.org/10.6342/NTU.2008.02583

摘要

目的：
針對末期非小細胞肺癌的患者，評估標靶藥物gefitinib治療與合併化學藥物治療的存活時間與醫療費用。以中央健康保險局為觀點，透過經濟評估與分析，提供衛生政策或藥品給付通則修訂時的參考依據。

設計：
單一醫學中心，前瞻性臨床試驗與回溯性病歷分析研究。

地點：
國立臺灣大學醫學院附設醫院。

對象：
2001年1月1日至2007年6月30日期間，初診斷為末期非小細胞肺癌的患者。臨床試驗組以第一線標靶藥物gefitinib或是第一線合併化學藥物治療作為病患分組依據。後線使用gefitinib藥物治療組以患者的病程中使用gefitinib藥物治療時期不同而分為第二線治療或第三線治療組。

方法：
以病人首次使用藥物的日期作為起始日期，於追蹤期間於院內的就診紀錄與費用，均視為治療肺癌的直接醫療成本，醫療費用的呈現為醫院向中央健保局申報的價格，只計算直接成本的醫療費用部份，不考慮間接成本與無形成本。病患的存活時間、死亡事件、整體存活率、疾病緩解期、治療藥物的組合內容皆納入治療效果的評估。統計分析以比例風險迴歸模式，找出可能影響醫療成本的因子，依據影響因子作分組病患的最低成本分析與成本效果分析。
結果：
研究期間內參與第一線gefitinib治療臨床試驗的106位病患，存活中位數22.4月，平均個人終身累積總費用850,231元，一年累積總費用752,374元，二年累積總費用1,236,669元；第一線治療期（gefitinib時期）的每月總費用為72,434元，第二線治療期54,937元，第三線治療期112,271元，緩和醫療期66,226元；於追蹤期間死亡患者有48名（45.3％），一年存活率31.3％，存活中位數9.6月，終身累積總費用最多人數7人（14.6％）分布於10- 20萬元。
參與第一線合併化學藥物治療臨床試驗的182位患者，存活中位數16.7月，平均個人終身累積總費用928,041元，一年累積總費用624,299元，二年累積總費用832,938元；第一線治療期的每月總費用為81,839元，第二線治療期63,767元，第三線治療期63,854元，緩和醫療期51,492元；於追蹤期間內死亡患者共157名（86.3%），存活中位數14.4月，終身累積總費用最多人數17人（10.8％）分布於80- 90萬元。
以gefitinib作後線治療的患者之中，33位第二線gefitinib治療的病患，自第一線藥物治療始起至最後追蹤日期的存活中位數36.7月，平均終身累積總費用1,271,733元，使用gefitinib時間6.6月，自使用gefitinib始起至最後追蹤日期的存活中位數為27.6月，gefitinib期間的醫療總費用571,401元，每月醫療總費用167,063元。70名第三線gefitinib治療的患者，自第一線藥物治療始起至最後追蹤日期的存活中位數28.6月，平均終身累積總費用1,328,475元，使用gefitinib時間7.1月，自使用gefitinib始起至最後追蹤日期的存活中位數為11.4月，gefitinib期間的醫療總費用455,200元，每月醫療總費用114,816元。
迴歸模式分析結果，發現影響患者的第一次疾病緩解期和終身累積費用的因子為第一線使用藥物組別、年齡、女性且腺癌。臨床試驗組中，年齡小於65歲、女性且腺癌的患者，第一線gefitinib組與第一線合併化學藥物治療組的成本效果差異比為每月26,859元。

結論：
我們的研究顯示影響末期非小細胞肺癌患者的醫療成本因子為第一線使用藥物組別、年齡、女性且腺癌；若年齡小於65歲、女性且腺癌的患者，第一線gefitinib組與第一線合併化學藥物治療組的成本效果差異小於平均每人每年GDP值，以醫療經濟而言，應屬可接受的範圍內，但仍須以患者與社會的福祉作為優先考量。

關鍵字

醫療經濟評估 ； 藥物經濟評估 ； 非小細胞肺癌 ； 標靶治療 ； 第一線gefitinib治療

並列摘要

Objective：
The objective of this study was to evaluate the clinical outcome and mean medical cost for patients treated with gefitinib or combination chemotherapy for advanced non-small-cell lung cancer（NSCLC）. Economic analysis was carried out based on the perspective of the Bureau of National Health Insurance（BNHI）in Taiwan to evaluate the cost and benefit of the treatments in order to provide references for health policy or guidelines for drugs price adjustment in the future.
Design：
This study consisted of a prospective clinical trial in conjunction with a retrospective chart-review using data from a single medical center.
Setting：
Data for this study was obtained from the National Taiwan University Hospital（NTUH）.
Study subjects：
Adult patients who had an initial diagnosis of advanced NSCLC between January 1, 2001 and June 30, 2007 were included in the study. The clinical trial group consisted of first line gefitinib treatment or combination chemotherapy patients. The rear use gefitinib group patients were categorized into second line or third line treatment according to their individual health states.
Methods：
The study spanned the period from the patients’ first drug-taking date to the censored date of the study, and all activities were assumed to be related to the treatment for NSCLC that will be absorbed into the medical management expense. The management costs represented costs reimbursed to NTUH from BNHI, and only direct costs were accounted. The survival time, death event, overall survival rate, time to progression, and treatment regimens were included in patients’ clinical assessment. Cox proportional hazard analysis was used to identify predictors for the management costs. The identified predictors were then utilized in the analyses of cost minimization and cost effectiveness.
Results：
During the study period, 106 patients were involved in the first line gefitinib therapy for the NSCLC trial. The median survival time was 22.4 months, and the mean lifetime total management cost was 850,231 NTD. One-year and two-year cumulative total costs were 752,374 NTD and 1,236,669 NTD, respectively. The cost for the first line gefitinib treatment period was 72,434 NTD per month, while that for the second line, third line, and palliative treatment periods were 54,937 NTD, 112,271 NTD, and 66,226 NTD, respectively. Forty-eight patients（45.3％）had deceased during our study period. Their 1-year survival rate was 31.3％, and their median survival time was 9.6 months. Their highest count in the number of patients for lifetime NSCLC treatment cost fell into the 100- 200 thousand NTD stratification—there was seven（14.6％）.
There were 182 patients involved in the first line combination chemotherapy for the NSCLC trial. The median survival time was 16.7 months, and the mean lifetime total management cost was 928,041 NTD. One-year and two-year cumulative total costs respectively were 624,299 NTD and 832,938 NTD. The cost of the first line treatment period was 81,839 NTD per month, while that of the second line, third line, and palliative treatment periods were 63,767 NTD, 63,854 NTD, and 51,492 NTD, respectively. There were 157 patients（86.3％）who had deceased within our study period. Their median survival time was 14.4 months, and the highest count for lifetime cost was 17 patients （10.8％）who fell into the 800- 900 thousand NTD stratification.
There were 33 end-stage NSCLC patients treated with second line gefitinib therapy. The median survival time was 36.7 months, the mean lifetime total treatment cost was 1,271,733 NTD, the average gefitinib duration was 6.6 months, the survival time after starting gefitinib was 27.6 months, the total cost of gefitinib period was 571,401 NTD, and the monthly cost was 167,063 NTD. There were 70 patients treated with the third line gefitinib therapy for compassionate use. Their median survival time was 28.6 months; mean lifetime total treatment cost, 1,328,475 NTD; average gefitinib duration, 7.1 months; survival time after starting gefitinib, 11.4 months; total cost of gefitinib period, 455,200 NTD; and monthly cost, 114,816 NTD.
Cox proportional hazard analysis showed that first line drug treatment option, age, gender and the status of adenocarcinoma were significant predictors for the first time to progression cost and the lifetime cumulative cost. Among the clinical trial study, for female patients with adenocarcinoma under the age of 65, the incremental cost effectiveness ratio （ICER） of first line gefitinib therapy in comparison with first line chemotherapy was 26,859 NTD per month.
Conclusions：
Our study showed that end-stage NSCLC patients’ management cost was associated with first line drug treatment option, age, gender and the presence or absence of adenocarcinoma. For patients who were female, under 65 years old and had adenocarcinoma, the difference between the ICER of first line gefitinib therapy and that of first line chemotherapy was smaller than Gross Domestic Product（GDP）per capital. This result appeared to be acceptable in terms of medical economics, but chiefly for the advantage of patients and societies should be the prior consideration.

並列關鍵字

Medical-economic analysis ； Pharmacoeconomic analysis ； Non-small cell lung cancer ； Target therapy ； first line gefitinib therapy

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