Cost-effectiveness of combination therapy of polatuzumab vedotin plus rituximab, cyclophosphamide, doxorubicin, and prednisolone for previously untreated diffuse large B-cell lymphoma in Japan.

AIM: The POLARIX trial showed that Pola + R-CHP (polatuzumab vedotin plus rituximab, cyclophosphamide, doxorubicin, and prednisolone) prolongs progression-free survival (PFS) in patients with previously untreated diffuse large B-cell lymphoma (DLBCL) compared with R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisolone), the conventional standard of care, with a similar safety profile. However, Pola + R-CHP has not been evaluated from the viewpoint of health economics in Japan. This study evaluates the cost-effectiveness of Pola + R-CHP for previously untreated DLBCL from a Japanese public healthcare payer's perspective. METHODS: A partitioned survival analysis model was constructed to estimate lifetime costs and effectiveness of Pola + R-CHP and R-CHOP in previously untreated DLBCL who had an International Prognostic Index score (IPI) score of ≥2. A parametric survival model was applied to data analyzed in the POLARIX trial to estimate the lifetime overall survival (OS) and PFS for each treatment. The parameters required for the model were based on the results of a literature search and expert opinion. RESULTS: The incremental cost-effectiveness ratio (ICER) of Pola + R-CHP vs. R-CHOP was JPY2,710,238 per quality-adjusted life year (QALY), less than the ICER of JPY7.5 million per QALY that is considered to be cost-effective based on the threshold of the Japanese cost-effectiveness evaluation system. One-way sensitivity analysis showed that the parameters influencing the results of the analysis were median PFS and the total cost per regimen of salvage chemotherapy, patient weight, and patient age. Probabilistic sensitivity analysis showed that the probability of Pola + R-CHP having superior cost-effectiveness was 99.2% when the reference value was JPY7.5 million. The results of scenario analysis suggested that prolongation of PFS was an important factor in the evaluation of cost-effectiveness in previously untreated DLBCL with or without prolongation of OS. CONCLUSIONS: This study suggests that Pola + R-CHP is a cost-effective treatment for previously untreated DLBCL in Japan under the public health insurance system.

Cost-effectiveness analysis of patent foramen ovale closure versus medical therapy alone after cryptogenic stroke.

BACKGROUND: Closure of a patent foramen ovale reduces the risk of recurrent stroke compared with medical therapy alone in young patients with cryptogenic strokes revealed by randomized control trials. Some cost-effectiveness analyses outside Japan have shown that patent foramen ovale closure is cost-effective, but no studies have examined cost-effectiveness in Japan. The objective of this study is to assess cost-effectiveness, from the perspective of a Japanese healthcare payer, of patent foramen ovale closure versus medical therapy alone for patients with patent foramen ovale related to cryptogenic strokes. METHODS: A cost-effectiveness study was conducted by developing a decision tree and a Markov model. Probabilities and a 5.9-year time horizon followed the RESPECT study. Utilities and costs were based upon published studies and assumptions. All assumptions were assessed by experts, including a cardiologist and a statistical expert. The target population comprised patients with cryptogenic stroke and patent foramen ovale, aged 60 years or younger. The model was discounted at 2.0% and its cycle was one month. A willingness-to-pay threshold is set at $50,000 / quality-adjusted life years (QALYs). Incremental cost-effectiveness ratio was evaluated. Then one-way sensitivity analyses as deterministic sensitivity analysis, and probabilistic sensitivity analyses were performed to assess data robustness. RESULTS: Incremental quality-adjusted life years, incremental costs, and incremental cost-effectiveness ratio were 0.464, $13,562, and $29,208 per QALY gained, respectively. One-way sensitivity analysis showed that the stable state utility score difference between patent foramen ovale closure and medical therapy had the largest impact on incremental cost-effectiveness ratio. Patent foramen ovale closure is cost-effective at a stable state utility score difference of >0.051, compared with medical therapy. Probabilistic sensitivity analyses demonstrated that patent foramen ovale closure was 50.3% cost-effective. CONCLUSIONS: Patent foramen ovale closure was cost-effective compared with medical therapy for Japanese patients with cryptogenic stroke who were ≤60 years.

A nationwide web-based survey of factors associated with depressive symptoms among Japanese workers.

BACKGROUND: Precarious employment has affected mental health, and limited data are available on the association of low stress tolerance with depressive symptoms among Japanese workers. AIMS: This study aimed to examine the relationship between stress tolerance and depressive symptoms among Japanese workers, including company employees, civil servants and self-employed persons in various industries. METHODS: We conducted a nationwide cross-sectional study. From March 26 to April 6, 2020, we performed a web-based survey of Japanese workers. The questionnaire included questions on socioeconomic factors, the SOC scale that assesses stress tolerance, the CES-D, and the EQ-5D-5L. Multivariate regression analyses were performed to determine the factors associated with depressive symptoms. RESULTS: We included 3,001 participants in the analysis. A high SOC score, adequate sleeping time and frequency of exercise were associated with higher depressive symptoms. Employment status and long working hours were not associated with depressive symptoms. Younger workers had lower SOC scores than older workers. An inverse correlation between the SOC score and CES-D score was found among Japanese workers. CONCLUSIONS: Improving stress tolerance among younger workers is needed to prevent worsening mental health regardless of employment status for Japanese workers.

Psychological impact of the state of emergency over COVID-19 for non-permanent workers: a Nationwide follow-up study in Japan.

BACKGROUND: The outbreak of COVID-19 has caused mental health problems and increased unemployment due to the economic recession. This survey aimed to assess the psychological impact of the state of emergency. We estimated changes in mental health, quality of life, and unemployment experience for general workers during the first COVID-19 outbreak in Japan. METHODS: We conducted a nationwide follow-up study. During the periods of March 26 to April 6, 2020 and June 26 to July 2, 2020, we used the internet to survey general workers aged 15 to 59 years in Japan. The questionnaire items covered employment status and socioeconomic factors, and we used the Center for Epidemiologic Studies Depression Scale (CES-D) and EQ-5D-5L to assess depression and health-related quality of life (HR-QOL), respectively. The differences in outcomes of permanent and non-permanent workers were analyzed using propensity score analysis. A multiple linear regression analysis was performed to examine the relationship between unemployment and CES-D scores. RESULTS: We included 2351 subjects in the analysis. Changes in both CES-D scores and utility were not significantly different between the two groups. However, a significant difference was found regarding the rate of unemployment, which was associated with higher CES-D scores. CONCLUSIONS: The present study demonstrated that the mental health of non-permanent workers was not negatively affected following the state of emergency due to COVID-19 in Japan. Unemployment is an important factor that influences the mental health of general workers.

Cost-effectiveness of BRCA1/2 mutation profiling to target olaparib use in patients with metastatic breast cancer.

Aim: Olaparib monotherapy improves progression-free survival in patients with metastatic breast cancer and BRCA1/2 mutations. We evaluated the cost-effectiveness of BRCA1/2 mutation profiling to target olaparib use. Methods: A Markov cohort model was generated to compare the 5-year cost-effectiveness of BRCA1/2 mutation profiling to target olaparib use. Results: The incremental cost-effectiveness ratio of BRCA1/2 mutation profiling plus olaparib monotherapy was JPY14,677,259/quality-adjusted life year (QALY) (US$131,047/QALY), compared with standard chemotherapy alone. Conclusion:BRCA1/2 mutation profiling to target olaparib use is not a cost-effective strategy for metastatic breast cancer. The strategy provides minimal incremental benefit at a high incremental cost per QALY. Hence, further cost reductions in the cost of both BRCA1/2 mutation profiling and olaparib are required.

Cost-effectiveness of combined serum anti-Helicobacter pylori IgG antibody and serum pepsinogen concentrations for screening for gastric cancer risk in Japan.

BACKGROUND: A combination of assays for the presence of serum anti-Helicobacter pylori IgG antibody (HPA) and serum pepsinogen (PG) concentrations can be used to screen for gastric cancer risk. In Japan, this "ABC method" is considered an effective means of stratifying gastric cancer risk. This study aimed to ascertain its cost-effectiveness for assessing gastric cancer risk. METHODS: A Markov model was constructed to compare the cost-effectiveness of two strategies for gastric cancer-risk screening over a 30-year period: the ABC method, which uses a combination of assessing the presence of HPA and measuring serum PG concentrations and scheduling endoscopies accordingly, and annual endoscopic screening. Clinical and epidemiological data on variables in the model were obtained from published reports. Analyses were made from the perspective of the Japanese health care payer. RESULTS: According to base-case analysis, the ABC method cost less than annual endoscopic screening (64,489 vs. 64,074 USD) and saved more lives (18.16 vs. 18.30 quality-adjusted life years). One-way analyses confirmed the robustness of the cost-effectiveness results. The probability that the ABC method is cost-effective in Japanese individuals aged 50 years was 0.997. CONCLUSIONS: A combination of HPA and serum PG assays, plus scheduling endoscopy accordingly, is a cost-effective method of screening for gastric cancer risk in Japan.

Cost-effectiveness of Paclitaxel + Ramucirumab Combination Therapy for Advanced Gastric Cancer Progressing After First-line Chemotherapy in Japan.

PURPOSE: The combination of paclitaxel + ramucirumab is a standard second-line treatment in patients with advanced gastric cancer. This therapy has been associated with increased median overall survival and progression-free survival compared with those with paclitaxel monotherapy. We evaluated the cost-effectiveness of paclitaxel + ramucirumab combination therapy in patients with advanced gastric cancer, from the perspective of health care payers in Japan. METHODS: We constructed a Markov model to compare, over a time horizon of 3 years, the costs and effectiveness of the combination of paclitaxel + ramucirumab and paclitaxel alone as second-line therapies for advanced gastric cancer in Japan. Health outcomes were measured in life-years (LYs) and quality-adjusted (QA) LYs gained. Costs were calculated using year-2016 Japanese yen (¥1 = US $17.79) according to the social insurance reimbursement schedule and drug tariff of the fee-for-service system in Japan. Model robustness was addressed through 1-way and probabilistic sensitivity analyses. The costs and QALYs were discounted at a rate of 2% per year. The willingness-to-pay threshold was set at the World Health Organization's criterion of ¥12 million, because no consensus exists regarding the threshold for acceptable cost per QALY ratios in Japan's health policy. FINDINGS: Paclitaxel + ramucirumab combination therapy was estimated to provide an additional 0.09 QALYs (0.10 LYs) at a cost of ¥3,870,077, resulting in an incremental cost-effectiveness ratio of ¥43,010,248/QALY. The incremental cost-effectiveness ratio for the combination therapy was >¥12 million/QALY in all of the 1-way and probabilistic sensitivity analyses. IMPLICATIONS: Adding ramucirumab to a regimen of paclitaxel in the second-line treatment of advanced gastric cancer is expected to provide a minimal incremental benefit at a high incremental cost per QALY. Based on our findings, adjustments in the price of ramucirumab, as well as improves in other clinical parameters such as survival time and adverse event in advanced gastric cancer therapy, are needed.

Economic impact of combination therapy with infliximab plus azathioprine for drug-refractory Crohn's disease: a cost-effectiveness analysis.

BACKGROUND: Combination therapy with infliximab (IFX) and azathioprine (AZA) is significantly more effective for treatment of active Crohn's disease (CD) than IFX monotherapy. However, AZA is associated with an increased risk of lymphoma in patients with inflammatory bowel disease. AIM: To evaluate the cost-effectiveness of combination therapy with IFX plus AZA for drug-refractory CD. METHODS: A decision analysis model is constructed to compare, over a time horizon of 1year, the cost-effectiveness of combination therapy with IFX plus AZA and that of IFX monotherapy for CD patients refractory to conventional non-anti-TNF-α therapy. The treatment efficacy, adverse effects, quality-of-life scores, and treatment costs are derived from published data. One-way and probabilistic sensitivity analyses are performed to estimate the uncertainty in the results. RESULTS: The incremental cost-effectiveness ratio (ICER) of combination therapy with IFX plus AZA is 24,917 GBP/QALY when compared with IFX monotherapy. The sensitivity analyses reveal that the utility score of nonresponding active disease has the strongest influence on the cost-effectiveness, with ICERs ranging from 17,147 to 45,564 GBP/QALY. Assuming that policy makers are willing to pay 30,000 GBP/QALY, the probability that combination therapy with IFX plus AZA is cost-effective is 0.750. CONCLUSIONS: Combination therapy with IFX plus AZA appears to be a cost-effective treatment for drug-refractory CD when compared with IFX monotherapy. Furthermore, the additional lymphoma risk of combination therapy has little significance on its cost-effectiveness.

Cost-effectiveness achieved through changing the composition of renal replacement therapy in Japan.

OBJECTIVE: The cost-effectiveness of renal replacement therapy (RRT) is affected by the composition of treatment. This study aimed to estimate the costs and outcomes associated with changing the composition of RRT modality over time. METHODS: By using clinical and cost data from a systematic review, a Markov model was developed to assess the costs and benefits of the four main treatments available for RRT in Japan. The model included direct health service costs and quality-adjusted life years (QALY). Sensitivity analyses were performed to assess the robustness of the results. RESULTS: Over the 15-year period of the model, the current composition of RRT (i.e., the base composition of RRT) was $84,008/QALY. The most cost-effective treatment was when the likelihood of a living donor transplant was increased by 2.4-times ($70,581/QALY). Compared with the base composition of RRT, dominant treatments with respect to cost-effectiveness were when the likelihood of a deceased donor transplant was increased by 22-times and when the likelihood of a pre-emptive living donor transplant was increased by 2.4-times. Little difference was found between these two treatments. One-way sensitivity analysis did not change the cost effectiveness except for costs of chronic hemodialysis and a living donor transplant in subsequent years. LIMITATIONS: It is difficult to increase the rate of transplant overall in the shorter term nationally and internationally. CONCLUSIONS: Appropriate distribution of all transplant options and hemodialysis is necessary to achieve the most cost-effective solution.