Japanese Journal of Clinical Oncology Advance Access originally published online on August 24, 2005
Japanese Journal of Clinical Oncology 2005 35(9):526-530; doi:10.1093/jjco/hyi144
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© 2005 Foundation for Promotion of Cancer Research
Treatment Cost of Pancreatic Cancer in Japan: Analysis of the Difference after the Introduction of Gemcitabine
1 Division of Hepatobiliary and Pancreatic Medical Oncology and 2 Division of Upper Abdominal Surgery, National Cancer Center Hospital East, Kashiwa, Chiba, Japan
For reprints and all correspondence: Hiroshi Ishii, National Cancer Center Hospital East, 6-5-1, Kashiwanoha, Kashiwa, Chiba 277-8577, Japan. E-mail: hirishii{at}east.ncc.go.jp
Received May 27, 2005; accepted July 10, 2005
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Abstract |
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 TOP Abstract INTRODUCTIONPATIENTS AND METHODSRESULTSDISCUSSIONReferences |
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Background: Recent advances in cancer chemotherapy have increased not only the survival rate but also the treatment cost, although there has been little interest in cost analyses in Japan.
Method: The actual cost of pancreatic cancer treatment was surveyed especially with respect to the difference after April 2001, which was the date that gemcitabine was introduced in Japan.
Results: A total of 113 patients were admitted consecutively from April 2000 to March 2002. Among the 113 patients, the total treatment cost over a lifetime was calculated in 54. In those 54 patients, the median treatment cost and survival time were $43 865 and 26.2 months for resectable disease (n = 14), $30 676 and 10.0 months for locally advanced disease (n = 21), and $29 255 and 4.8 months for metastatic disease (n = 19), respectively. Of the 54, 26 patients were admitted before April 2001 (Group A) and the remaining 28 were admitted thereafter (Group B). There were significantly more patients who received gemcitabine chemotherapy in Group B (19 of the 28) than in Group A (none of the 26). The median treatment cost and survival times were $35 744 and 7.4 months in Group A, and $35 226 and 8.8 months in Group B, respectively, whereas the total cost of anticancer agents was significantly higher in Group B than in Group A.
Conclusion: Although cost of gemcitabine is about 18-fold higher than 5-fluorouracil in Japan, the total costs after gemcitabine introduction did not tend to become higher in our hospital, probably because of simplification in examinations and shorter hospitalization.
Key Words: pancreatic neoplasm • cost analysis • treatment cost • chemotherapy • investigational new drug application
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INTRODUCTION |
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TOPAbstractINTRODUCTIONPATIENTS AND METHODSRESULTSDISCUSSIONReferences |
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Pancreatic cancer (PC) is the fifth leading cause of death due to cancer in Japan, and in 2001 there were 19 397 deaths owing to this malignancy (1). Although surgical resection offers the opportunity for cure, only a small minority of PC patients are candidates for surgery. Moreover, even for these selected patients, the prognosis remains unfavorable because of post-operative recurrence. For a long time, chemotherapy for recurrent or unresectable PC had only limited value and there had been no regimen superior to 5-fluorouracil (5-FU) alone (2,3). However, in the late 1990s gemcitabine (GEM) showed significantly better results in survival time compared to 5-FU (4,5). Accordingly, GEM has been accepted as the first-line chemotherapy treatment for advanced PC in many countries, and in Japan GEM was introduced into hospitals in April 2000 (6). Although the incremental survival advantage of GEM over 5-FU is relatively small (median 1–2 months) (4,5,7), the cost of GEM is about 18-fold higher than 5-FU in Japan.
There has been little interest in cost analyses in cancer treatments in Japan, probably because Japanese people invariably join public health insurance programs and all hospital and doctor fees have been guarantied according to medical piecework (not a prospective payment system) by the government. However, total medical costs have increased year by year and the estimate of national medical care expenditure was $284 billion in 1999, i.e. $2240 per person, which represented 8% of the national income (8). Although the government has started to work on medical cost cutting and have tried a Japanese version of the Diagnosis Related Group/Prospective Payment System in a few model hospitals since 1998, most Japanese hospitals including National Cancer Center, employ the conventional payment system (the sum of piecework) at present. Because the prospective payment system will become widely prevalent in Japan, this may be the last chance to survey an actual cost of PC treatment according to the conventional payment system.
With this imperative, we surveyed the actual cost of PC treatment especially with respect to the difference after the introduction of a new drug, GEM. To our knowledge, this is the first report of a cost analysis of PC in Japan.
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PATIENTS AND METHODS |
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TOPAbstractINTRODUCTIONPATIENTS AND METHODSRESULTSDISCUSSIONReferences |
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PATIENTS
Since the day of our hospital opening in July 1992, we have recorded all patients admitted to our division. This database has been updated generally three times a week at our morning conference. We obtained an invasive ductal PC patient list from the database, and surveyed all case records between 1 April 2000 and 30 March 2002 (April 2001 ± 1 year) in the list. The reason we chose this period was to investigate the impact of GEM, which has been introduced to Japanese hospitals since April 2001. We collected each patient's baseline data at the time of diagnosis and their treatment histories. These included gender, age, computed tomography (CT) stage, site of metastasis, performance status according to the Eastern Cooperative Oncology Group criteria, serum level of carcinoembryonic antigen and carbohydrate antigen (CA) 19-9, primary treatment modalities, treatment costs (calculated from patient receipts), and date and cause of death.
TREATMENT
According to the CT stage at presentation, patients with resectable disease underwent resection, and we did not perform any adjuvant therapies until recurrence after surgery. As for locally advanced disease, we performed a combination of intraoperative and external-beam radiotherapy with 5-FU before April 2001 (9). After April 2001, we performed hypofractionated external-beam radiotherapy followed by GEM chemotherapy in selected patients with locally advanced PC (10). We had performed single agent chemotherapy for metastatic or recurrent PC in general by using 5-FU before April 2001, and GEM thereafter (7). Until November 2000, combination therapy of hepatic arterial infusion of 5-FU and external-beam radiation for the primary tumor had been performed in selected patients with no metastases other than in the liver (11).
Patients received a detail explanation about the studies and gave written informed consent after approval of the protocols by the Institutional Review Board of the National Cancer Center.
TREATMENT COST
In Japan, upon joining an organization, the employees and the families of those employed by government offices, and the private sector and public organizations automatically join the health insurance program. People who are not members of the Health Insurance Union have been required to join the National Health Insurance program, which is operated by municipalities throughout the nation, since 1961. The costs for medical services are regulated by the government and are the same throughout Japan, and people can receive medical services with 20–30% of the medical costs as their payment, based on this social security system.
Treatment costs are calculated from patient receipts of our hospital. Other than the uniform treatment costs regulated by the government, the costs in the current study included various actual expenses, such as private room charges, the cost of daily meals during hospitalization and medical certificates for private health insurance. Namely, the total costs meant total payments to the hospital for patients who did not join the Japanese health insurance system.
In the current study, treatment costs were described in terms of United States dollars ($) with the exchange rate at the time of data fixation, 30 June 2004, i.e. $1 = 109 Japanese yen (¥). For example, the cost of pancreaticoduodenectomy is $4825 (¥526 000), and 1 gram of GEM is $255 (¥27 825), in Japan.
ANALYSIS AND STATISTICS
We surveyed the treatment costs and survival data of patients, and examined the relationship among patients' characteristics, treatment costs and survival time. Total treatment cost from the first hospitalization to the death or 30 June 2004 (date of the data fixation), including all costs of every hospital visits and the last hospitalization for terminal care, was defined as the total treatment cost over a lifetime (TCL) in the current study.
Overall survival was measured from the first day of treatment to the date of death or last contact. All patients were censored on 30 June 2004, 14 months after treatment of the last patient. Survival curves were calculated by the Kaplan–Meier method. Differences in survival among subgroups classified by each factor were evaluated by log-rank tests.
Since the treatment costs were not shown to have a normal distribution, the Mann–Whitney test was used to compare the overall differences of them among the subgroups. Frequency analysis was performed with Fisher's exact test for 2 x 2 tables, and with the 
2-test for 3 x 2 tables.
All analyses were performed using the statistical software SPSS 11.0J for Windows. Statistical significance was defined as a two-sided P-value of 0.05 or less.
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RESULTS |
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TOPAbstractINTRODUCTIONPATIENTS AND METHODSRESULTSDISCUSSIONReferences |
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A total of 113 PC patients were admitted during the 2 years survey. Among the 113 patients, the TCL was calculated in 54 patients, i.e. 49 who died in our hospital and 5 who were alive until 30 June 2004. The TCL was not available in the remaining 59, mainly because they went to other hospitals for terminal care. There was no difference in their backgrounds and the survival between the former 54 and the latter 59 (Table 1) other than the pretreatment CA 19-9 level, which was higher in the former 54.
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In the 54 patients, TCL ranged from $4586 to $89 681 and the quartiles at 25, 50 and 75% were $24 046, $35 351 and $48 119, respectively. According to the CT stage, the median of TCL and survival time were $43 865 and 26.5 months for the resectable, $29 255 and 10.0 months for the locally advanced, and $30 676 and 4.8 months for the metastatic, respectively.
DIFFERENCES AFTER APRIL 2001
Among the 54 patients available for TCL analysis, 26 were admitted before April 2001 (Group A) and the remaining 28 were admitted thereafter (Group B). The patients' characteristics in each group are shown in Table 2. The frequencies of locally advanced disease and gemcitabine chemotherapy were higher in Group B. As for the patients with locally advanced disease, GEM chemotherapy have been an alternative treatment choice in our hospital since April 2001. Accordingly, there was no significant difference between Groups A and B in the other baseline background factors, including primary treatment.
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Table 3 shows several costs and survival times in Groups A and B. The total cost for anticancer agents was significantly higher in Group B than in Group A, whereas there were no significant differences as for overall survival and TCL between the groups. Among the cost of anticancer agents, a fraction of that in the outpatient clinic was the main cause that made the cost in Group B significantly higher than in Group A. Although there was no significant difference in hospital stay in the first admission between the two groups, the cost for the first admission in Group A tended to be high compared to that in Group B. The cost for the first admission included various imaging tests (Table 4). An average number of imaging tests per patient in the first admission was 5.0 in Group A and 3.9 in Group B. In 40 patients with locally advanced or metastatic disease, the median cost and hospital stay in the first admission in Group B ($11 493 and 37 days, respectively) were lower than those in Group A ($22 218 and 59 days, respectively), although the differences were not statistically significant (P = 0.055 and P = 0.156, respectively).
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DISCUSSION |
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TOPAbstractINTRODUCTIONPATIENTS AND METHODSRESULTSDISCUSSIONReferences |
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As known from previous reports (12,13), the disease stages are correlated with PC treatment costs in Japan. When compared to the total treatment cost of metastatic disease, that of locally advanced and resectable disease was 1.2- to 1.6-fold and 1.6- to 1.9-fold higher, respectively (Table 5). The relative relationship between disease stage and treatment cost was at almost the same proportion in the three countries. As for the absolute treatment costs, however, there were relatively large differences among the three. The average cost of PC treatment in Japan was about twice of that in Sweden, and three quarters of that in the United States. This is probably due to differences of social security and health insurance systems in each country.
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Other than the survey of actual PC treatment costs in Japan, economic and medical differences after the introduction of GEM were our main interest in the current study. Before conducting the current study, we hypothesized that the TCL had gone up since the introduction of the expensive new drug, GEM.
However, the TCL did not increase as a result of GEM introduction. Possible reasons were simplification in pretreatment imaging examinations, shorter hospitalization and an early outpatient-based treatment. The frequency of imaging tests before treatment decreased except for ultrasonography, CT and magnetic resonance imaging after the GEM introduction. Because we were aware that the three imaging tests were necessary and sufficient for staging evaluation after the GEM introduction, other invasive examinations, such as endoscopic retrograde cholangiopancreatography or angiography, were optional, especially in advanced cases. Moreover, hospitalization becomes shorter because GEM chemotherapy is feasible for an outpatient treatment. Accordingly, total costs for anticancer agents increased after GEM, especially in the outpatient clinic fraction.
To reduce the costs of cancer treatment, therefore, simplification in examinations and shortening of hospitalization may be effective. However, those efforts may have an apparent limitation, because new expensive agents, such as bevacizumab, will increase the PC chemotherapy costs in the near future, as seen in colorectal cancer chemotherapy costs at present.
In summary, the total cost of PC treatment correlated well with disease staging, and there was no international difference in its proportion. The total costs after GEM did not tend to be high in our hospital, probably because of the simplification in examinations and short hospitalization. We believe it will be necessary to promote cost analysis and to make an effort to reduce treatment costs as well as to develop new effective and expensive agents, because health care resources are becoming scarce in many countries.
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Acknowledgments |
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The authors thank our secretary, Ms Yuki Fujishiro for her devoted preparations of cost data.
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References |
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TOPAbstractINTRODUCTIONPATIENTS AND METHODSRESULTSDISCUSSIONReferences |
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