Ichiro Arakawa

Cost-minimization analysis of sequence changes between FOLFIRI and FOLFOX6 therapy for advanced colorectal cancer in Japan

BACKGROUND Randomized, controlled trials (RCTs) in 220 patients with advanced colorectal cancer reported no significant differences in survival periods between folinic acid/5-fluorouracil/irinotecan (FOLFIRI) and folinic acid/5-fluorouracil/oxaliplatin (FOLFOX6) therapies, irrespective of the treatment sequence. Based on a literature search, an economic assessment of both treatments given in 1 of 2 sequences (FOLFIRI and FOLFOX6, or FOLFOX6 and FOLFIRI) has not been conducted in Japan. OBJECTIVE The present cost-minimization analysis used a mathematical Markov model to assess health care costs of these 2 treatment sequences from the perspective of National Health Insurance (NHI) in Japan. METHODS The analysis simulated the expected costs resulting from the influence of treatment sequence in a hypothetical cohort of 10,000 patients with nonresectable advanced colorectal cancer over a period of 100 months using a hypothetical Markov model. Clinical parameters were obtained from the RCTs. Cost parameters included those for physical examination, medication, and personnel. Medication and physical examination costs were based on 2008 NHI drug prices and medical service fees, respectively. Costs were discounted at a monthly rate of 0.4575% (equivalent to an annual rate of 3%). The influence of each parameter (clinical and cost parameters) was assessed using a probabilistic sensitivity analysis by the 10,000-time Monte Carlo simulation. RESULTS When FOLFIRI was used as the initial treatment in this analysis, costs to the NHI were reduced. On analysis of the influence of each parameter, the expected reduction in costs, compared with FOLFOX administered as the initial treatment, was significant ( 7,787,828 yen [95% CI, 6,098,517 yen - 9,499,952 yen]). CONCLUSIONS The findings of this cost-minimization analysis suggest that using FOLFIRI followed by FOLFOX versus the reverse strategy produced cost savings from the perspective of the NHI in Japan. However, differences in adverse-events profiles may warrant treatment adjustments in individual patients.

Cervical Cancer Screening With Human Papillomavirus Dna and Cytology in Japan

Objective The aim of this study was to determine the value of human papillomavirus (HPV) testing for primary cervical cancer screening in Japan. Methods In total, 5065 women who underwent primary screening with cytology and HPV between January 2005 and December 2006 were enrolled. In the baseline phase, these women were stratified by age, and the rates of HPV-positive and abnormal cytology were compared between women younger than and older than 30 years. In the follow-up phase, women aged 20 to 69 years and cytology negative for intraepithelial lesions or malignancy at baseline were followed up until December 2011 (n = 2383). Progression to grade 2/3 cervical intraepithelial neoplasia or worse (CIN2+/CIN3+) was compared between the HPV-positive and HPV-negative groups. Results In the baseline phase, HPV-positive rates were significantly higher in women younger than 30 years at 20.7% (95% confidence interval [CI], 18.4–22.9; 255/1234) compared with women 30 years or older at 7.2% (95% CI, 6.4%–8.0%; 275/3831; P < 0.001). However, there was no statistical difference for high-grade squamous intraepithelial lesion or worse rates between them, at 2.7% (95% CI, 1.8%–3.6%; 33/1234) and 2.4% (95% CI, 1.9%–2.9%; 91/3831), respectively, P = 0.55. In the follow-up phase, the rate of progression to CIN2+/CIN3+ was significantly higher in the HPV-positive group than in the HPV-negative group (P < 0.001). Moreover, relative risk of progression to CIN2+ was 15.9 times higher in the HPV-positive group, and that of progression to CIN3+ was 16.1 times higher in the HPV-positive group. Conclusions Human papillomavirus testing is a useful test for predicting progression to CIN and is recommended as a primary screening tool. However, screening with cytology alone is still appropriate for younger women, younger than 30 years, because HPV testing yields more false-positive results in younger women.

Evaluation of health-related quality of life for hypothesized medical states associated with cervical cancer.

BACKGROUND When evaluating health-economics for cervical cancer prevention policies in Japan, it is important to use Japanese value settings. This study aimed to obtain preference-based measures (preference measures) for hypothesized health states among healthy Japanese women, and to examine differences between the EuroQol-5D (EQ-5D) and standard gamble (SG) instruments. MATERIALS AND METHODS The investigation was performed among female students at a nursing university. We used written hypothetical scenarios describing three grades of cervical intraepithelial neoplasia (CIN) and eight stages of cervical cancer, both at diagnosis and after medical intervention. Preference measures were evaluated using both EQ-5D and SG. RESULTS We received responses from 136 women. The mean number of respondents per stage was 24.6 (SD: 2.7). At diagnosis, average EQ-5D scores for CIN1, CIN2, CIN3, IA1, IA2, IB1, IB2, IIA, IIB, III, and IV stages were 0.84 (0.14), 0.78 (0.12), 0.73 (0.10), 0.78 (0.12), 0.72 (0.12), 0.63 (0.13), 0.64 (0.12), 0.68 (0.08), 0.62 (0.13), 0.55 (0.21), and 0.18 (0.24), respectively. Using one-way analysis of variance with the Tukey-Kramer method for multiple comparisons (each stage vs. CIN1), we found significant differences for IB1 and more advanced stages (p<0.05). After medical intervention, corresponding EQ-5D scores were 0.84 (0.12), 0.81 (0.12), 0.84 (0.12), 0.80 (0.15), 0.78 (0.11), 0.64 (0.15), 0.63 (0.15), 0.71 (0.15), 0.50 (0.17), 0.52 (0.17), 0.21 (0.28). The multiple comparisons identified significant differences for IB1 and more advanced stages, excepting IIA (p<0.05). SG evaluations were more variable and relatively higher than EQ-5D evaluations. CONCLUSIONS We obtained preference measures for three grades of CIN1-3 and eight stages of cervical cancer. In combination with appropriate sensitivity analyses, these preference measures will provide a basis for an economic evaluation of cervical cancer prevention in Japan. We suggest that EQ-5D is appropriate for cost-utility analysis of this topic.

Regarding 'HPV vaccination for cervical cancer prevention is not cost-effective in Japan'.

The authors of this letter read the article of Isshiki et al. (2014) on the cost-benefit analysis of HPV vaccination for cervical cancer prevention, and they found it interesting and unique. The article concluded that HPV vaccination at the price of US

Development of endometrioma after cervical conization

500 is not cost-effective, but becomes cost-effective at half that price. This conclusion misevaluates prophylactic cervical cancer programmes by both vaccination and screening in Japan, as the authors found a number of issues in the scenario analysis that Isshiki conducted. Therefore, this article is not suitable for forming political decisions. The authors would like to identify critical issues by discussing Model A, Model B, and the methodology of economic evaluation. The aim of our comment is to help make Isshiki’s analysis more accurate and clear and to provide comprehensive information to support political decision-making by Japanese central and regional authorities. Regarding Model A, it was assumed that screening with cytology was conducted every year from the age of 30 using base-case analysis. Based on current guidance of policy by the Japan regulatory authority, however, women should be screened with cytology every two years (Hamashima et al., 2010). Hence, given that frequency of screening was a factor in the scenario analysis, our concern is that screening costs in ‘Model A’ are overestimated. The article should also have taken into consideration the prophylactic effectiveness of screening for precancerous conditions (it was assumed that women are screened 11 times). Moreover, the authors could not find an appropriate reason why loss of earnings was calculated for only five years in this article, relating to the use of 13.163 of the Leibniz coefficient (at the age of 45, the feasible estimate of working years is 22). With regard to Model B, the authors suggest that the article should incorporate cost of screening weighted by 23.7% (OECD, 2011) because the uptake rate of screening is based on screening not only with but also without vaccinations. It is also unclear why the article did not consider direct costs for mass-screening, treatment, and palliative care (home care may also be relevant), even though it stated that a woman was diagnosed with cervical cancer of stage IIIB at age of 40 and treated with hysterectomy, irradiation, and anticancer drugs in Model B. According to ‘Methods for economic evaluation of health care’ ( Drummond et al., 2005), all the important and relevant costs identified and related to prevention LETTER to the EDITER

Cost-effectiveness of aprepitant in Japanese patients treated with cisplatin-containing highly emetogenic chemotherapy

Abstract The association between cervical conization and subsequent development of endometriosis is uncertain. The objective of this study was to estimate the incidence rate of ovarian endometrioma after cervical conization and to determine factors associated with the development of endometrioma. One hundred forty-two patients who underwent cervical conization at the University of Tokyo Hospital between January 2006 and December 2013 were included in the study. Their medical records were retrospectively studied until April 2015. The incidence rate of postconization endometrioma was calculated. Patients’ characteristics (age, parity, preoperative and postoperative diagnosis and observation period) were analyzed. Six patients developed endometrioma after the cervical conization, and the incidence rate of endometrioma among patients who underwent cervical conization was 10.8 per 1000 person-year (95%CI 3.6–20.5). Patients’ age, percent of nulliparous, postoperative diagnosis and observation period were not associated with the development of postconization endometrioma. A preoperative diagnosis with invasive cancer (p < 0.05) was significantly associated with the development of postconization endometrioma. The incidence rate of endometrioma among patients who underwent cervical conization in the current study was higher than that reported population.

A Cost-Effectiveness Analysis of Gemcitabine plus Cisplatin Versus Gemcitabine Alone for Treatment of Advanced Biliary Tract Cancer in Japan

Chemotherapy‐induced nausea and vomiting (CINV) remains a major adverse event in cancer chemotherapy. Although aprepitant is effective in preventing CINV, an increment in financial burden for uniform use of aprepitant is a concern. The aim of the present study was to define the cost‐effectiveness of aprepitant from the perspective of the Japanese National Health Insurance system. Based on the results of a randomized phase II trial comparing an aprepitant‐containing regimen versus a nonaprepitant regimen in Japanese patients who received cisplatin‐containing highly emetogenic chemotherapy, a decision analytic model was developed. The incremental cost‐effectiveness ratio (ICER) was calculated both in the outpatient care setting (OCS) and in the inpatient care setting (ICS). The use of the aprepitant‐containing regimen was associated with improved quality of life compared with the nonaprepitant regimen, with an increment in quality‐adjusted life years (QALY) of 0.0016. The incremental total medical costs associated with the use of the aprepitant regimen were lower in the OCS than in the ICS, 6192 JPY (56.92 USD) and 9820 JPY (90.27 USD), respectively. The ICER was calculated as 3 906 698 JPY (35 910 USD) per QALY gained in the OCS and 6 195 781 JPY (56 952 USD) per QALY gained in the ICS. Cost‐effectiveness of the aprepitant‐containing antiemetic therapy was limited to the OCS, considering the threshold of willingness‐to‐pay commonly accepted (5 million JPY [45 960 USD] in Japan and 50 000 USD in the USA). The efficacy of aprepitant offsets the costs for revisiting clinics or rehospitalization added with rescue medications in the OCS.