回溯性研究第一線合併化學藥物治療末期非小細胞肺癌病患的醫療費用及其結構分析

Abstract

肺癌分別是男性與女性罹患癌症死因第二位及第一位，其中約有90%的病患屬於非小細胞肺癌，將近一半以上在診斷時已經屬於無法用手術切除的末期階段，直到現在尚未有任何化療藥物組合證實療效最好，而末期非小細胞肺癌的治療包括昂貴的化療藥費，因此希望可以瞭解在現階段的第一線合併化學藥物治療下，病患的存活時間及所花醫療費用。 臺大醫院每年初診斷為末期非小細胞肺癌且符合進入臨床試驗條件的病患，將近有二分之一會進入臨床試驗，過去研究結果大部分指出進入臨床試驗會花去較多費用，但研究結果尚不確定且美國與臺灣的醫療生態不同，因此本研究希望透過臺大醫院的資料來瞭解進入或未進入臨床試驗病患的存活時間及醫療花費，並比較近五年來病患醫療費用與存活時間的趨勢。 2000-2005年間在臺大醫院接受第一線合併化學藥物治療且符合進入臨床試驗條件的病患共有440位，其存活中位數為14.6個月，一年存活率為57.9%；平均個人半年總費用為327,099元，總藥費為212,420元，化療藥費為167,434元；累積到一年之後，總費用為470,259元，總藥費為292,733元，化療藥費為222,123元。在追蹤期間死亡病患終身總費用為665,964元，終身藥費和化療藥費分別為386,313元及274,024元。 再依照病患是否曾參與第一線合併化療臨床試驗分組；一年存活率臨床試驗組 vs. 非臨床試驗組為67.5% vs. 47.5%，存活中位數為17.5個月vs.非臨床試驗組11.7個月，統計上有顯著差異(p=0.02)。兩組病患從開始化療藥物治療至之後半年、一年、兩年、終身的累積費用分別為：半年累積總費用試驗組比非試驗組低10.6% (306,892元vs. 343,201元, p=0.06)，一年累積總費用試驗組比非試驗組高1.8%，(475,276元vs. 467,057元, p=0.78)，兩年累積總費用試驗組比非試驗組高9.6% (619,001元vs. 564,851元, p=0.13)；終身費用試驗組比非試驗組高11.5% (696,579元 vs. 624,684元, p=0.14)；臨床試驗組病患較多在之後接受第二、三線的抗癌藥物治療，臨床試驗組病患比非試驗組總費用的ICER為14,208元/月。 有些臨床試驗是由廠商提供新藥(Trial-free組)，因此病患在第一線合併化療藥費會減少，以此對臨床試驗病患分組(其餘病患屬於另一組Trial-T106)，Trial-free組的總費用累積到18個月內都是最低的一組，可見第一線治療少了一種化療藥費對於之後的累積費用有一定程度的影響。 在Phase III的臨床試驗中，病患會被隨機分派到試驗組(Trial-trial)或是控制組(Trial-control)，控制組的治療方式與非臨床試驗組類似，兩組存活時間在統計上沒有差異；使用新藥或新療程的Trial-trial組的存活時間比非試驗組顯著較長。2000-2003年間存活時間有較長的趨勢，而醫療成本部分則是2004年比起2000年顯著的升高。 費用結構方面，總藥費中大部分都是來自於化療藥費；臨床試驗組的門診費用比非試驗組顯著的較高，而非試驗組則在住院花費較高。分析影響病患醫療費用的因子，較長的存活時間、接受第二線以上化療、接受放療、接受手術、有心臟疾病等因子會顯著增加費用，而參與由廠商提供免費新藥的試驗則會顯著的使醫療費用減少。 根據本研究的結果，進入臨床試驗病患存活時間較長，所花化療藥費較高，但經過存活時間校正之後，非臨床試驗組比臨床試驗組高；終身成本效果分析得到臨床試驗組比非試驗組的ICER為14,208元/月，增加的費用應是在醫療經濟上可接受的範圍之內。

Lung cancer is the first and second cause of cancer death for women and men in Taiwan. Nonsmall cell lung cancer accounts for almost 90% of all lung tumors. More than half of them belong to unresectable endstage when they are newly diagnosed. Currently, there is still no chemotherapy regimen considered to be the best. Because chemotherapy costs are expensive, we want to know the survival probability and the treatment costs of endstage nonsmall cell lung cancer patients who were treated with first line combination chemotherapy. Almost half of National Taiwan University Hospital patients who were newly diagnosed of endstage nonsmall cell lung cancer were eligible for participating in clinical trials every year. Most of the previous studies suggested that clinical trials increase in treatment costs over standard treatment. Since the results were still not clear enough and the differences that lie in American and Taiwan’s medical environment, we want to evaluate the effect of participation in nonsmall cell lung cancer clinical trials on patients’ survival and treatment costs in the current study. We also want to evaluate the trend of patients’ survival and medical costs in last five years. There were 440 patients who were treated with first line combination chemotherapy and who were eligible for clinical trials at National Taiwan University Hospital during 2000 to 2005. The median survival for these patients was 14.6 month and the 1-year survival rate was 57.9%. The average six-month cumulative treatment cost for patients was 327,099NTD, the drug cost was 212,420NTD and the chemotherapy cost was 167,434 NTD; the average 1-year cumulative treatment cost for patients was 470,259NTD, the drug cost was 292,733NTD and the chemotherapy cost was 222,123NTD. The average lifetime cost among the patients who were deceased during our study period was 665,964 NTD, and the drug cost and chemotherapy cost were 386,313 NTD and 274,024 NTD. We rearranged the patients into two subgroups by patients participated in the clinical trials or not, Trial group and Nontrial group. For the Trial group, the one-year survival rate was 67.5%, in comparison with 47.5% for Nontrial group. The median survival for Trial patients was significantly longer than Nontrial patients (17.5 month vs. 11.7 month, p=0.02). The average six-month cumulative treatment cost was 10.6% lower for Trial patients than Nontrial patients (306,892NTD vs. 343,201NTD, p=0.06). The average one-year cumulative treatment cost was 1.8% higher for Trial patients than Nontrial patients (475,276NTD vs. 467,057 NTD, p=0.78). The average two-year cumulative treatment cost was 9.6% higher for Trial patients than Nontrial patients (619,001NTD vs. 564,851NTD, p=0.13). The average lifetime cost among the patients who were deceased during our study period was 11.5% higher for Trial patients than Nontrial patients (696,579NTD vs. 624,684NTD, p=0.14). Patients participated in clinical trials received more second or third line chemotherapy. The ICER of Trial group was 14,208 NTD/month. In addition, we rearranged patients who participated in clinical trials into two subgroups according to whether the drugs were provided by pharmaceutical industries or not. The cumulative costs for patients participated in clinical trials with free drug (Trial-free group) were the lowest within 18 months. The first line chemotherapy costs had some effects on the cumulative treatment costs. The treatment regimens of Trial patients who were randomized into control group (Trial-control group) were quite the same with the standard treatments of Nontrial group. There was no significant difference in median survival between Trial-control group and Nontrial group. The median survival of Trial group patients who were randomized into trial group was significantly longer than that of Nontrial group patients. There was an increase trend in patients’ survival rate during 2000-2003. The results displayed that medical costs incurred in 2004 were significantly higher than in 2000. We also found that most of the drug costs come from chemotherapy. Trial group incurred more outpatient costs and Nontrial group incurred more inpatient costs. Patients’ median survival, receiving second line chemotherapy treatment, radiotherapy, surgery, patients with heart disease and those who received free drug while participating in clinical trials were all significant predictors of treatment costs. The median survival of patients participated in clinical trials was significantly longer than patients who were eligible for clinical trials but not participating in clinical trials. Trial group patients also incurred more chemotherapy costs and total treatment costs. After adjustment with survival time, the treatment costs among Nontrial group were higher than Trial group. The ICER of Trial group was 14,208 NTD/month and it should be within the acceptable range of health economics.