Cost-Effectiveness Analysis of Cyclin-Dependent Kinase 4/6 Inhibitor Palbociclib for Inoperable or Recurrent Breast Cancer.

BACKGROUND: Palbociclib and endocrine therapy has been approved to treat hormone receptor-positive/human epidermal growth factor receptor 2-negative inoperable or recurrent breast cancer in Japan. However, this cotherapy imposes an economic burden on both patients and society because of its high cost. In this study, we assessed the cost-effectiveness of cotherapy with palbociclib and fulvestrant compared to fulvestrant monotherapy for inoperable or recurrent breast cancer. METHODS: The three-state Markov model was built by taking into count health stats in inoperable or recurrent breast cancer. The clinical outcomes of the therapies were drawn from published randomized controlled trials. Total regimen cost was calculated from medical receipts of patients at the Yamagata University Hospital. The cost-effectiveness was evaluated by the incremental cost-effectiveness ratio(ICER), in case that it was below 400,000 Yen per month. Markov chain Monte Carlo simulation was performed to assess probability. RESULTS: Acquisition cost of palbociclib and fulvestrant and fulvestrant monotherapy was 6,209,554 JPY and 780,870 JPY, and 25.7 and 22.8 months were achieved, respectively. ICER for the cotherapy was 1,847,721 JPY/quality adjusted life month(QALM)gained. CONCLUSIONS: The palbociclib and fulvestrant therapy provided better health outcomes than conventional fulvestrant monotherapy, but were costly and suggested to be less cost-effective.

Factors contributing to the ceiling effect of the EQ-5D-5L: an analysis of patients with prostate cancer judged "no-problems".

PURPOSE: The goal of the present study was to determine factors related to a ceiling effect (CE) on the EQ-5D-5L among Japanese patients with prostate cancer (PC). METHODS: An existent cross-sectional observational study dataset was used. Patients were ≥ 20 years of age and diagnosed with PC. For CE determinants on the EQ-5D-5L, we excluded possible "full-health" patients flagged by the EQ-VAS (score = 100) and/or FACT-P (score = 156) instruments. We then divided them into binary variables: A CE group (EQ-5D-5L score = 1) and others (< 1). The associations between CE, sociodemographic and medical characteristics, and FACT-P subscale scores were examined using a multivariate LASSO selection followed by a binomial logistic regression analysis performed to calculate odds ratios (ORs) and 95% confidence intervals (CIs). RESULTS: A total of 362 patients were analyzed. The LASSO selection variables, including all obtained variables, were as follows: age, palliative treatment, FACT-P physical well-being, and PC subscale score. Statistically significant variables predicting CE were palliative treatment (OR 0.23; 95% CI 0.09-0.60), physical well-being (OR 1.54; 95% CI 1.34-1.76), and PC subscale (OR 1.08; 95% CI 1.03-1.14). CONCLUSIONS: This study revealed that palliative treatment and two FACT-P physical well-being and PC subscale scores were positively related to CE on the EQ-5D-5L. To our knowledge, this is the first study to examine predictors of CE on the EQ-5D-5L. The present results may be helpful for facilitating the consideration of "bolt-on" studies from the standpoint of PC patients.

Cost-utility analysis of aprepitant for patients who truly need it in Japan.

PURPOSE: Neurokinin-1 receptor antagonist (NK1RA) is recommended to prevent chemotherapy-induced nausea and vomiting (CINV) in patients who receive highly or moderately emetogenic chemotherapy (HEC or MEC, respectively). We previously reported that aprepitant, an NK1RA, was needed to control CINV in 43% and 12% of patients who received HEC and MEC, respectively (Support Care Cancer 23:905-912, 2015). To elucidate the cost-effectiveness of aprepitant in these patients, a cost-utility analysis according to the necessity of aprepitant was performed. METHODS: A decision-analytic model was developed according to the necessity of aprepitant and CINV responses in both acute and delayed phases of chemotherapy. Probabilities of health states and medical costs were derived from the results of the abovementioned trial. RESULT: In patients who received HEC and needed aprepitant, the incremental cost-effectiveness ratio (ICER) with aprepitant, relative to the regimen with no aprepitant, was 7912 US dollars (USD) per quality-adjusted life year (QALY) gained, which was far below the commonly accepted threshold of 50,000 USD/QALY. The ICER was 27,457 USD/QALY in patients who received MEC and needed aprepitant. In contrast, in patients who received HEC or MEC but did not need aprepitant, the ICER was 175,959 or 478,844 USD/QALY, respectively. CONCLUSION: Regardless of whether a patient received HEC or MEC, aprepitant use was highly cost-effective for patients who truly needed it. These results warrant further research to predict the necessity of NK1RA treatment before initiating emetogenic chemotherapies.

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

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.

Cost-effectiveness of the recommended medical intervention for the treatment of dysmenorrhea and endometriosis in Japan.

BACKGROUND AND OBJECTIVE: This study aims to assess the cost-effectiveness of early physician consultation and guideline-based intervention to prevent endometriosis and/or disease progression using oral contraceptive (OC) and progestin compared to follow-up of self-care for dysmenorrhea in Japan. METHODS: A yearly-transmitted Markov model of five major health states with four sub-medical states was constructed. Transition probabilities among health and medical states were derived from Japanese epidemiological patient surveys and converted to appropriate parameters for inputting into the model. The dysmenorrhea and endometriosis-associated direct costs included inpatient, outpatient visit, surgery, and medication (OC agents, over-the-counter drugs), etc. The utility measure for patients with phase I-IV endometriosis comprised a visual analogue scale. We estimated the cost per quality-adjusted life year (QALY) at a time horizon of 23 years. An annual discount rate at 3% for both cost and outcome was considered. RESULTS: The base case outcomes indicated that the intervention would be more cost-effective than self-care, as the incremental cost-effectiveness ratio (ICER) yielded 115,000 JPY per QALY gained from the healthcare payers' perspective and the societal monetary value (SMV) was approximately positive 3,130,000 JPY, favoring the intervention in the cost-benefit estimate. A tornado diagram depicting the stochastic sensitivity analysis of the ICER and SMV from both the healthcare payers' and societal perspectives confirmed the robustness of the base case. A probabilistic analysis resulting from 10,000-time Monte Carlo simulations demonstrated efficiency at willingness-to-pay thresholds in more than 90% of the iterations. CONCLUSIONS: The present analysis demonstrated that early physician consultation and guideline-based intervention would be more cost-effective than self-care in preventing endometriosis and/or disease progression for patients with dysmenorrhea in Japan.

Development of endometrioma after cervical conization.

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.

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.

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

OBJECTIVES: This study assessed the cost-effectiveness of combination treatment with gemcitabine and cisplatin compared to treatment with gemcitabine alone for advanced biliary tract cancer (BTC) in Japan. METHODS: A monthly transmitted Markov model of three states was constructed based on the Japan BT-22 trial. Transition probabilities among the health states were derived from a trial conducted in Japan and converted to appropriate parameters for our model. The associated cost components, obtained from a receipt-based survey undertaken at the Aichi Medical University Hospital, were those related to inpatient care, outpatient care, and treatment for BTC. Costs for palliative care and treatment of adverse events were obtained from the National Health Insurance price list. We estimated cost-effectiveness per quality-adjusted life year (QALY) at a time horizon of 36 months. An annual discount of 3 % for both cost and outcome was considered. RESULTS: The base case outcomes indicated that combination therapy was less cost-effective than monotherapy when the incremental cost-effectiveness ratio (ICER) was approximately 14 million yen per QALY gained. The deterministic sensitivity analysis of the ICER revealed that the ICER of the base case was robust. A probabilistic analysis conducted with 10,000-time Monte Carlo simulations demonstrated efficacy at the willingness to pay threshold of 6 million yen per QALY gained for approximately 33 % of the population. CONCLUSION: In Japan, combination therapy is less cost-effective than monotherapy for treating advanced BTC, regardless of the statistical significance of the two therapies. Useful information on the cost-effectiveness of chemotherapy is much needed for the treatment of advanced BTC in Japan.

[Comparison of the Cost-Effectiveness of the SOX and COX Regimens in Patients with Unresectable Advanced and Recurrent Colorectal Cancer Using a Clinical Decision Analysis Approach].

Phase III clinical trials have comfirmed that the S-1 plus oxaliplatin(SOX)is inferior to the capecitabine plus oxaliplatin (COX)regimen in the treatment of metastatic colorectal cancer.On the basis of these findings, we compared, using a clinical decision analysis-based approach, the cost-effectiveness of the SOX and COX regimens.Herein, we simulated the expected effects and costs of the SOX and COX regimens using the markov model.Clinical data were obtained from Hong's 2012 report.The cost data comprised the costs for pharmacist labor, material, inspection, and treatment for adverse event, as well as the total cost of care at the advanced stage.The result showed that the expected cost of the SOX and COX regimen was 1,538,330 yen, and 1,429,596 yen, respectively, with an expected survival rate of 29.18 months, and 28.63 months, respectively.The incremental cost-effectiveness ratio of the SOX regimen was 197,698 yen/month; thus, the SOX regimen was found to be more cost-effective that the COX regimen.

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.

Clinical application of removable partial dentures using thermoplastic resin. Part II: Material properties and clinical features of non-metal clasp dentures.

This position paper reviews physical and mechanical properties of thermoplastic resin used for non-metal clasp dentures, and describes feature of each thermoplastic resin in clinical application of non-metal clasp dentures and complications based on clinical experience of expert panels. Since products of thermoplastic resin have great variability in physical and mechanical properties, clinicians should utilize them with careful consideration of the specific properties of each product. In general, thermoplastic resin has lower color-stability and higher risk for fracture than polymethyl methacrylate. Additionally, the surface of thermoplastic resin becomes roughened more easily than polymethyl methacrylate. Studies related to material properties of thermoplastic resin, treatment efficacy and follow-up are insufficient to provide definitive conclusions at this time. Therefore, this position paper should be revised based on future studies and a clinical guideline should be provided.

Development of the Japanese version of the COPD Assessment Test.

BACKGROUND: We aimed to develop the Japanese version of the COPD Assessment Test (TM) (CAT), which was recently developed in overseas countries, to measure the health status of patients with chronic obstructive pulmonary disease (COPD) and to validate its psychometric properties. METHODS: The original CAT was translated to Japanese through linguistic validation. Then, an Internet-based survey was conducted by including 301 Japanese patients with COPD who were over 40 years of age and had a history of smoking, to assess the reliability and validity of the translated CAT. RESULTS: The Japanese CAT was shown to have high internal consistency (Cronbach's α coefficient: 0.891). The assessment using the Japanese CAT was highly correlated with assessment using the COPD-specific St. George's Respiratory Questionnaire (r = 0.820). The assessment also showed correlation between the Japanese CAT and a generic health-related quality of life (QOL) questionnaire (SF-12v2). CONCLUSION: The Japanese version of the CAT has high reliability and validity, and can be expected to serve as a short and simple questionnaire for precise assessment of the health status of Japanese patients with COPD.

[Pharmacoeconomic evaluation of combination therapy with dutasteride and α1 blocker for treatment of benign prostatic hyperplasia in Japan].

The cost-effectiveness of combination therapy with an α1 blocker and dutasteride in benign prostatic hyperplasia (BPH) was analyzed in comparison with α1 blocker monotherapy. A Markov model with seven health states related to BPH was constructed with 4-year and 10-year time horizons and from the entire payers perspective. The transition probabilities among different health states input into the model were mainly derived from CombAT Study data, while cost parameters were estimated from a clinical database including DPC claims. Effectiveness was defined as quality adjusted life year (QALY). The cost-effectiveness of combination therapy was assessed by the incremental cost-effectiveness ratio (ICER) threshold (6 to 7 million Japanese yen (JPY)/QALY gained). For a base-case analysis, combination therapy produced an incremental effectiveness versus monotherapy of 0.050 and 0.097 QALYs at 4 years and 10 years, respectively, while the concomitant incremental costs were estimated to be 257,172 and 579,908 JPY, respectively. The ICERs for combination therapy versus monotherapy calculated at 4 years and 10 years were 5,119,007 and 5,974,495 JPY/QALY gained, respectively, both below the acceptable ICER threshold. Sensitivity analyses revealed that the ICER tended to decrease with greater BPH severity. These findings suggest that combination therapy with an α1 blocker and dutasteride would be more cost-effective in BPH than α1 blocker monotherapy and more efficient in moderate-to-severe BPH.

Adjuvant endocrine therapy in post menopausal women: pharmacological evaluation using decision analysis approach in a Japanese hospital setting.

An optimal adjuvant endocrine therapy is yet to be established for post menopausal women with hormone receptor positive breast cancer. The current therapeutic options include initial, switch, and extended adjuvant therapies. We aimed to determine the most cost-effective therapeutic option using the clinical decision analysis method. It was suggested that aromatase inhibitor monotherapy in initial adjuvant therapy is the most cost-effective and optimal adjuvant endocrine therapy for post menopausal women with hormone receptor-positive breast cancer.

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.