Cost-effectiveness analysis of transcatheter aortic valve implantation in aortic stenosis patients at low- and intermediate-surgical risk in Japan.

OBJECTIVE: To analyze the cost-effectiveness of transcatheter aortic valve implantation (TAVI) using the SAPIEN 3 (Edwards Lifesciences, Irvine, CA) compared to surgical aortic valve replacement (SAVR) in low- and intermediate-risk patients from a Japanese public healthcare payer perspective. METHODS: A Markov model cost-effectiveness analysis was developed. Clinical and utility data were extracted from a systematic literature review. Cost inputs were obtained from analysis of the Medical Data Vision claims database and supplemented with a targeted literature search. The robustness of the results was assessed using sensitivity analyses. Scenario analyses were performed to determine the impact of lower mean age (77.5 years) and the effect of two different long-term mortality hazard ratios (TAVI versus SAVR: 0.9-1.09) on both risk-level populations. This analysis was conducted according to the guidelines for cost-effectiveness evaluation in Japan from Core 2 Health. RESULTS: In intermediate-risk patients, TAVI was a dominant procedure (TAVI had lower cost and higher effectiveness). In low-risk patients, the incremental cost effectiveness ratio (ICER) for TAVI was ¥750,417/quality-adjusted-life-years (QALY), which was below the cost-effectiveness threshold of ¥5 million/QALY. The ICER for TAVI was robust to all tested sensitivity and scenario analyses. CONCLUSIONS: TAVI was dominant and cost-effective compared to SAVR in intermediate- and low-risk patients, respectively. These results suggest that TAVI can provide meaningful value to Japanese patients relative to SAVR, at a reasonable incremental cost for patients at low surgical risk and potentially resulting in cost-savings in patients at intermediate surgical risk.

Aortic Stenosis (AS) is the most common valvular heart disease in Japan, and, if left untreated, severe symptomatic AS (sSAS) is associated with a dramatic increase in mortality and morbidity. Transcatheter Aortic Valve Implantation (TAVI) is a minimally invasive treatment option for replacing the aortic valve in patients with sSAS and has been associated with similar or better outcomes compared to Surgical Aortic Valve Replacement (SAVR), which involves open-heart surgical replacement of the aortic valve. The objective of this study was to compare the costs and health outcomes associated with TAVI compared to SAVR in Japanese patients deemed low- or intermediate-risk for surgery. Despite the expanding use of TAVI in Japan, a cost-effectiveness analysis (CEA) does not exist that evaluates the economics of TAVI with the current generation SAPIEN 3 implant in patients with low- and intermediate-risk from a public perspective. Our study suggests that TAVI represents strong value for money among low- and intermediate-risk patients in Japan: compared to SAVR, TAVI is associated with better clinical outcomes and quality of life for patients, at a reasonable additional cost for low-risk patients and at a lower cost for intermediate-risk patients.

Cost-Effectiveness Analysis of Vedolizumab Compared with Other Biologics in Anti-TNF-Naïve Patients with Moderate-to-Severe Ulcerative Colitis in Japan.

BACKGROUND: Vedolizumab (VDZ) was approved by the Japanese Ministry of Health, Labor and Welfare in 2018 for the treatment of patients with moderate-to-severe active ulcerative colitis (UC). The comparative cost-effectiveness of VDZ compared with other biologics is unknown in Japan. This information could be useful for decision makers at the time of repricing biologics for the treatment of patients with moderate-to-severe UC. OBJECTIVE: The aim was to assess the cost-effectiveness of VDZ versus other branded biologics for the treatment of patients with moderate-to-severe UC who were anti-tumor necrosis factor (TNF)-naïve, from the Japanese public healthcare payer perspective. METHODS: A hybrid decision tree/Markov model was developed to predict the number of patients who achieved response and remission at the end of the induction phase and sustained it during the maintenance phase, translating this into quality-adjusted life-years (QALYs) and costs. Treatment-related adverse events, discontinuation and surgery, and their impact on QALYs and costs were also modeled. A systematic literature review and network meta-analysis were conducted to estimate the comparative efficacy of each treatment versus placebo. Rates of adverse events, surgery, surgery complications, and utilities were from the literature. Costs (2018 Japanese yen) were obtained from the Japanese National Health Insurance drug price list and medical fee table and local claims databases. Clinical and economic outcomes were projected over a lifetime and discounted at 2% annually. RESULTS: Over a lifetime, VDZ yielded greater QALYs and cost savings compared with golimumab and was cost-effective compared with adalimumab and infliximab (incremental cost-effectiveness ratios ¥4,821,940 and ¥4,687,692, respectively). Deterministic and probabilistic analyses supported the robustness of the findings in the base-case analysis, indicating that VDZ was either dominant or cost-effective in most scenarios and replications. The main limitations of this analysis include excluding tofacitinib and infliximab biosimilar as comparators, health-state utility estimates were obtained from population studies in the United Kingdom, and the impact of subsequent (i.e., second-line) biologic treatment was not evaluated. CONCLUSION: Our analysis suggests that VDZ is dominant or cost-effective compared with other branded biologics for the treatment of anti-TNF-naïve patients with moderate-to-severe UC in Japan.

Health-related quality of life outcomes and economic burden of inflammatory bowel disease in Japan.

PURPOSE: Previous Japanese studies have not compared health-related quality of life (HRQoL), work productivity and activity impairment, health care resource utilization (HRU), and costs in inflammatory bowel disease (IBD) patients with non-IBD controls, leading to insufficient evidence regarding IBD's true burden. The aim of this study was to examine the impact of IBD on patient-reported outcomes and costs among Japanese adults (≥18 years). PATIENTS AND METHODS: This retrospective cross-sectional study used data from the 2012-2014 Japan National Health and Wellness Survey (N=83,505). HRQoL (SF-36v2), work productivity and activity impairment (work productivity and activity impairment-General Health Questionnaire), HRU, and annual costs were compared between respondents with IBD (n=441) and non-IBD controls (n=82,944), and within IBD subtypes (Crohn's disease [CD] and ulcerative colitis [UC]) using chi-square and ANOVA tests. RESULTS: Mental Component Summary (MCS), Physical Component Summary (PCS), and health state utility (Short-Form-6 Dimensions [SF-6D]) scores were significantly lower in IBD respondents than in controls (differences of 2.2 points, 2.6 points, and 0.041 points, respectively; all P<0.001). However, only differences in SF-6D scores reached the minimally important difference threshold. Furthermore, IBD-diagnosed respondents reported greater absenteeism, presenteeism, overall work productivity loss and activity impairment, and HRU than controls (all P<0.001). Consequently, direct and indirect costs were 3-fold and 1.5-fold higher in IBD-diagnosed respondents than in controls (both, P<0.001). Additionally, CD-diagnosed respondents had lower MCS, PCS, and SF-6D scores (all P<0.01) and higher direct costs (P<0.001) than UC-diagnosed respondents. CONCLUSION: IBD and its subtype CD were associated with lower HRQoL, greater impairment to work and non-work activities, HRU, and costs among Japanese adults. This reinforces the general consensus that IBD patients, specifically those diagnosed with CD, require support from their family and society to combat the disease.

Health-related quality of life outcomes, economic burden, and associated costs among diagnosed and undiagnosed depression patients in Japan.

PURPOSE: Depression is associated with substantial health and economic burden. This study examined the impact of diagnosed and undiagnosed depression on health-related outcomes and costs among Japanese adults. METHODS: A retrospective, observational study was conducted using 2012-2014 Japan National Health and Wellness Survey (N=83,504) data. Differences between respondents diagnosed with depression (n=2,843) and undiagnosed with depression (weighted n=2,717) and controls without depression (weighted n=2,801) in health-related quality of life, impairment to work productivity and daily activities (Work Productivity and Activity Impairment Questionnaire), health care resource utilization, and annual costs were evaluated. Propensity score weighting and weighted generalized linear models were used to compare groups on the outcome variables, after adjusting for covariates. RESULTS: Overall, respondents with undiagnosed depression had significantly better outcomes than those diagnosed with depression, but significantly worse outcomes than controls (for all, P<0.001). The mean Mental Component Summary scores were lower in the diagnosed group when compared with undiagnosed respondents and controls (33.2 vs 34.5 vs 48.6). Similar findings were obtained for mean Physical Component Summary (49.2 vs 49.5 vs 52.8) and health state utility scores (0.61 vs 0.62 vs 0.76). Additionally, the diagnosed group reported greater absenteeism (13.1 vs 6.6 vs 2.5%), presenteeism (41.4 vs 38.1 vs 18.8%), overall work productivity impairment (47.2 vs 41.1 vs 20.2%), and activity impairment (48.4 vs 43.3 vs 21.1%) than the undiagnosed and control groups, respectively. Consistently, patients with diagnosed depression had higher annual per patient direct (1.6-fold) and indirect costs (1.1-fold) than those in the undiagnosed depression group. CONCLUSION: Diagnosed depression was associated with lower health-related quality of life and greater impairment in work productivity and daily activities, higher health care resource utilization, and higher costs, compared with undiagnosed respondents and controls. These study findings suggest a need for greater awareness of depression symptoms among Japanese adults, which is needed to facilitate proper diagnosis and treatment.

Health-related outcomes, health care resource utilization, and costs of multiple sclerosis in Japan compared with US and five EU countries.

PURPOSE: Multiple sclerosis (MS) imposes a huge burden on patients. This study examined the relationship between MS and health-related and economic burden in Japan; secondarily, health status was compared across patients with MS in Japan, US, and five European Union (5EU) countries (France, Germany, Italy, Spain, and UK). METHODS: A retrospective cross-sectional study was conducted using self-reported data from 2009 to 2014 Japan National Health and Wellness Survey (n=145,759). Health status, work productivity loss, activity impairment, health care resource utilization, and annual costs associated with MS (n=85) were compared with controls without MS (n=145,674). Propensity score matching and multivariable linear regressions determined the effect of MS after controlling for confounders. Health status in Japan was also compared with that of 5EU (n=62) and US (n=67) patients with MS. RESULTS: Patients with MS in Japan reported significantly worse health status via mental component summary score (MCS; 40.1 vs 45.8) and physical component summary score (PCS; 41.4 vs 51.2) and health state utility scores (0.63 vs 0.74; all P<0.001). They also reported more absenteeism (12.0% vs 3.7%), presenteeism (33.8% vs 19.8%), overall work impairment (40.9% vs 21.6%), and activity impairment (43.6% vs 24.0%), with higher indirect costs (¥2,040,672/US $20,102 vs ¥1,076,306/US$10,603) than controls (all P<0.001). Patients with MS reported higher resource use, including provider visits (8.0 vs 4.7), emergency room visits (0.03 vs 0.1), and hospitalizations (2.7 vs 0.69) in the past 6 months, with higher direct costs (¥3,670,906/US$36,162 vs ¥986,099/US$9,714) than controls (all P<0.001). Finally, Japanese patients with MS reported lower MCSs and higher PCSs than their US and 5EU counterparts. CONCLUSION: MS in Japan is associated with poor health status and high work productivity loss, resource use, and costs, underscoring the need for improved treatment, especially vis-à-vis mental health, when comparing Japanese patients with their 5EU and US counterparts.

Health-related quality-of-life, work productivity, and economic burden among patients with Parkinson's disease in Japan.

AIMS: This study aimed to characterize the burden of Parkinson's disease (PD) by examining health-related quality-of-life (HRQoL), impairments to work productivity and daily activities, healthcare resource use, and associated costs among Japanese patients with PD. MATERIALS AND METHODS: This retrospective cross-sectional study used data from the 2009-2014 Japan National Health and Wellness Survey (NHWS) (n = 144,692). HRQoL (Short Form 36-Item Health Survey version 2), impairments to work productivity and daily activities (Work Productivity and Activity Impairment Questionnaire), healthcare resource utilization, and annual costs were compared between respondents with PD (n = 133) and controls without PD (n = 144,559). The effect of PD on outcomes was estimated using propensity score weighting and multivariable regression models. RESULTS: HRQoL was lower in patients with PD compared to the control group, with reduced physical (41.3 vs 51.3) and mental (35.7 vs 45.4) component summary scores and health state utility scores (0.62 vs 0.77; p < .001 for all). Patients with PD also reported higher levels of absenteeism (19.3% vs 3.3%), presenteeism (45.2% vs 18.5%), overall work impairment (52.8% vs 20.3%), and activity impairment (49.6% vs 20.8%) than controls without PD (p < .001 for all). In addition, patients with PD had higher healthcare resource utilization, direct (¥3,856,921/$37,994 vs ¥715,289/$7,046), and indirect (¥2,573,938/$25,356 vs ¥902,534/$8,891) costs compared with controls without PD (p < .001 for both). LIMITATIONS: Data were cross-sectional and did not allow for causal inferences. Although the NHWS demographically represents the Japanese adult population, it is unclear whether it adequately represents the adult population with PD in Japan. CONCLUSIONS: PD was associated with poorer HRQoL, greater work productivity loss, and higher direct and indirect costs. The findings suggest that an unmet need exists among patients with PD in Japan. Improving PD treatment and management could benefit both patients and society.

Cost-effectiveness of a pentavalent rotavirus vaccine in Japan.

OBJECTIVE: To evaluate the impact of universal vaccination with a pentavalent rotavirus vaccine (RV5) on the healthcare burden and costs associated with rotavirus gastroenteritis (RGE) in Japan. METHODS: The model included a hypothetical cohort of 1,091,156 children followed for their first 5 years of life. In the absence of universal vaccination, there were 19 deaths, 78,000 hospitalizations, and 678,000 outpatient visits due to RGE. The efficacy of RV5 is based on international clinical trial data, which was similar to the efficacy observed in clinical trials conducted in Japan. The primary outcome measure is the cost per quality-adjusted-life-year (QALY) gained. In the base case, the QALY loss per 1000 RGE episodes included 2.2 for children and 1.8 per parent. RESULTS: Universal vaccination is projected to reduce hospitalizations by 92%, outpatient visits by 74%, and work-loss days by 73%. For the base case analysis, the total vaccination cost was ¥26 billion. The estimated reduction in medical costs was ¥16 billion. Of 2500 QALYs gained with the vaccination program, approximately half are directly attributed to the child. In the base case analysis, the incremental cost-effectiveness ratio (ICER) for vaccination vs. no vaccination is ¥4 million and ¥2 million per quality-adjusted life year (QALY) gained from the healthcare payer and societal perspectives, respectively. The ICERs are ¥8 million and ¥4 million if parental disutilities are excluded. KEY LIMITATION: The QALY decrements for children and parents were evaluated using different instruments, and the QALY decrements do not vary based on episode severity. Given the interdependence between children and their parents, excluding parental disutilities may under-estimate the impact of RGE. CONCLUSION: Universal vaccination with RV5 in Japan is projected to have a substantial public health impact and may be cost-effective from both the payer and societal perspectives if parental disutilities are included in the cost-effectiveness ratios.

The Cost-Effectiveness Analysis of a Quadrivalent Human Papillomavirus Vaccine (6/11/16/18) for Females in Japan.

OBJECTIVE: We assessed the epidemiological and economic impact of a quadrivalent human papillomavirus (HPV) (6/11/16/18) vaccine for females in preventing cervical cancer, cervical intraepithelial neoplasia grades 2 and 3 (CIN 2/3), cervical intraepithelial neoplasia grade 1 (CIN 1), and genital warts in Japan by using a transmission dynamic model. METHODS: A published mathematical model of the transmission dynamics of HPV infection and disease was adapted for Japan. Model inputs were used from Japan or the Asia/Pacific region when available; otherwise, the default values in the original model were used. The transmission dynamic model was used to assess the epidemiological and economic impact of a quadrivalent HPV (6/11/16/18) vaccine for females in preventing cervical cancer, CIN 2/3, CIN 1, and genital warts in Japan.Maintaining current cervical cancer screening practices, we evaluated two strategies: routine vaccination of females by age 12 years (S1), and S1 combined with a temporary (5 years) female catch-up program for age 12 to 24 years (S2). The vaccine coverage rate was 80% for the routine and 50% for the catch-up vaccination programs. RESULTS: Compared with no vaccination, both vaccination strategies significantly reduced the incidence of HPV 6/11/16/18-related disease. The most effective strategy was S2. By using this strategy over 100 years in the Japanese population, the estimated cumulative percentage reduction in incident HPV 6/11/16/18-related genital warts-female, genital warts-male, cervical CIN 1, CIN 2/3, and cervical cancer cases was 90% (2,113,723 cases), 86% (2,082,637 cases), 72% (263,406 cases), 71% (1,328,366 cases), and 58% (323,145 cases), respectively. The cost-effectiveness ratios were JPY 1,244,000, and JPY 1,205,800 per quality-adjusted life-year gained for S1 and S2 compared with no vaccination, respectively, over a time horizon of 100 years. CONCLUSION: We conclude that a quadrivalent HPV vaccination program for females can reduce the incidence of cervical cancer, CIN, and genital warts in Japan at a cost-per-quality-adjusted life-year ratio within the range defined as cost-effective.