Cost-effectiveness Analysis of Apixaban against Warfarin for Stroke Prevention in Patients with Nonvalvular Atrial Fibrillation in Japan

Abstract Purpose The aim of this study was to evaluate the cost-effectiveness of apixaban compared with to warfarin, current standard of care, for stroke prevention in patients with nonvalvular atrial fibrillation (NVAF) in Japan. Methods A previously published lifetime Markov model was adapted to evaluate the cost-effectiveness of apixaban compared with warfarin in patients with NVAF in Japan. In the same model, the costs associated with each clinical event and background mortality were replaced with Japanese data. Whenever available, some of the utility parameters were derived from Japanese published literature. Lifetime horizon was selected to evaluate the value of the treatment benefit (stroke prevention) against potential risks (such as major bleedings) among patients with NVAF. Direct medical cost, long-term care cost, and quality-adjusted life years (QALYs) were calculated from the payers' perspective. Findings Compared with warfarin, treatment with apixaban was estimated to increase life expectancy by 0.231 year or 0.240 QALYs while treatment cost increased by ¥511,692 (US $5117 at an exchange rate of US$1 = ¥100). The incremental cost-effectiveness ratio was ¥2,135,743 per QALY (US $21,357 per QALY). On the basis of the results of the probabilistic sensitivity analysis, when the willingness-to-pay threshold was set at approximately ≥¥2,250,000 (US$22,500) per QALY, the probability of apixaban being cost-effective was ≥50%. Assuming a willingness-to-pay threshold of ¥5,000,000 (US $50,000) and ¥6,700,000 (US$67,000) in Japan, the probability of apixaban being cost-effective was 85% and 91%, respectively. Conclusion Although most participants in the Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation (ARISTOTLE) trial used for the efficacy data of apixaban in the model were non-Japanese patients, the impact of the limitations on our results was considered small, and our results were deemed robust because of the additional effect in Japanese patients compared with that in the global population according to the subanalysis of Japanese patients in the trial. Therefore, based on an adaptation of a published Markov model, apixaban is a cost-effective alternative to warfarin in Japan for stroke prevention among patients with NVAF

Use of the index of pulmonary vascular disease for predicting long-term outcome of pulmonary arterial hypertension associated with congenital heart disease

AimsLimited data exist on risk factors for the long-term outcome of pulmonary arterial hypertension (PAH) associated with congenital heart disease (CHD-PAH). We focused on the index of pulmonary vascular disease (IPVD), an assessment system for pulmonary artery pathology specimens. The IPVD classifies pulmonary vascular lesions into four categories based on severity: (1) no intimal thickening, (2) cellular thickening of the intima, (3) fibrous thickening of the intima, and (4) destruction of the tunica media, with the overall grade expressed as an additive mean of these scores. This study aimed to investigate the relationship between IPVD and the long-term outcome of CHD-PAH.MethodsThis retrospective study examined lung pathology images of 764 patients with CHD-PAH aged <20 years whose lung specimens were submitted to the Japanese Research Institute of Pulmonary Vasculature for pulmonary pathological review between 2001 and 2020. Clinical information was collected retrospectively by each attending physician. The primary endpoint was cardiovascular death.ResultsThe 5-year, 10-year, 15-year, and 20-year cardiovascular death-free survival rates for all patients were 92.0%, 90.4%, 87.3%, and 86.1%, respectively. The group with an IPVD of ≥2.0 had significantly poorer survival than the group with an IPVD <2.0 (P = .037). The Cox proportional hazards model adjusted for the presence of congenital anomaly syndromes associated with pulmonary hypertension, and age at lung biopsy showed similar results (hazard ratio 4.46; 95% confidence interval: 1.45–13.73; P = .009).ConclusionsThe IPVD scoring system is useful for predicting the long-term outcome of CHD-PAH. For patients with an IPVD of ≥2.0, treatment strategies, including choosing palliative procedures such as pulmonary artery banding to restrict pulmonary blood flow and postponement of intracardiac repair, should be more carefully considered

Cost-Effectiveness Analysis of Etanercept 25 mg Maintenance Therapy After Treatment With Etanercept 50 mg for Moderate Rheumatoid Arthritis in the PRESERVE Trial in Japan

Objectives: To use Markov modeling to estimate the cost-effectiveness of treatment with etanercept 25 mg once weekly plus methotrexate (MTX) in Japanese patients with rheumatoid arthritis who had achieved remission or low disease activity with etanercept 50 mg once weekly plus MTX. Methods: Effectiveness data were estimated based on results from a clinical trial (PRESERVE) in patients with rheumatoid arthritis who had achieved remission or low disease activity and who were then randomized to receive etanercept 25 mg plus MTX or placebo plus MTX. A Markov model was established and included flare rates of 21% and 62% in the etanercept 25 mg and placebo groups, respectively. EQ-5D was calculated using an ordinary least-squares model that included the health assessment questionnaire disability index and pain visual analog scale. Worsening of the health assessment questionnaire score over 1 year was estimated to be 0.047 for patients with flare, and when associated with radiographic progression it was estimated to increase by 0.006 and 0.025 in the etanercept 25 mg and placebo groups, respectively. A cycle length of 1 year was applied to calculate the cumulative cost and effectiveness for a 10-year time span. Results: Compared with the placebo group, the quality-adjusted life-years for the etanercept 25 mg group was increased by 0.841. The incremental cost-effectiveness ratio was Y6 173 772. Conclusion: These results suggest that maintenance treatment with etanercept 25 mg is cost-effective

Comparison of four value sets derived using different TTO and DCE approaches: application to the new region-specific PBM, AP-7D

Abstract Background AP-7D is a newly developed preference-based measure (PBM) in East and Southeast Asia. However, no value set has been established yet. Comparison of the characteristics of value sets obtained by different methods is necessary to consider the most appropriate methodology for valuation survey of AP-7D. Method We surveyed the general population’s preference of AP-7D health states by four valuation methods (a) composite time trade-off (cTTO); (b) simple discrete choice experiment (DCE); (c) DCE with duration; and (d) ternary DCE. In Japan, we collected approximately 1,000 samples for cTTO tasks through a face-to-face survey and 2,500 samples for each of the three DCE tasks. Respondents were selected through quota sampling based on the sex and age. The cTTO data were analyzed using a linear mixed and tobit model; the DCE data were analyzed using a simple and panel conditional logit model. Where the results of the analysis showed inconsistencies, a constrained model was used. Results Since all the unconstrained models, except simple DCE, showed one or more inconsistencies, the constrained model was used for the analyses. The minimum values for the models were as follows: TTO model, -0.101; simple DCE model, -0.106; DCE with duration model, -0.706; ternary DCE model, -0.306. The score for the DCE with the duration model was much lower than that for the other models. Although the value sets for AP-7D differed among the four valuation methods, the ternary DCE model showed intermediate characteristics between those of the cTTO and DCE with duration models. As compared with to EQ-5D-5L, the distributions of all the scores on the Japanese AP-7D moved to the left. Although “Energy” was one of the domains with the least influence on the AP-7D score in all four models, “Burden to others” had the largest impact on the preferences. Conclusion We constructed four value sets using different TTO and DCE methods. Our findings are expected not only to contribute to the development of AP-7D, but also other preference-based measures

Budget Impact Analysis of Treatment Flow Optimization in Epilepsy Patients: Estimating Potential Impacts with Increased Referral Rate to Specialized Care

**Objectives:** We developed a Markov model to simulate a treatment flow of epilepsy patients who refer to specialized care from non-specialized care, and to surgery from specialized care for estimation of patient distributions and expenditures caused by increasing the referral rate for specialized care. **Methods:** This budget impact analysis of treatment flow optimization in epilepsy patients was performed as a long-term simulation using the Markov model by comparing the current treatment flow and the optimized treatment flow. In the model, we simulated the prognosis of new onset 5-year-old epilepsy patients (assuming to represent epilepsy occurring between 0 and 10 years of age) treated over a lifetime period. Direct costs of pharmacotherapies, management fees and surgeries are included in the analysis to evaluate the annual budget impact in Japan. **Results:** In the current treatment flow, the number of refractory patients treated with four drugs by non-specialized care were estimated as 8766 and yielded JPY5.8 billion annually. However, in the optimized treatment flow, the number of patients treated with four drugs by non-specialized care significantly decreased and who continued the monotherapy increased. The costs for the four-drug therapy by non-specialized care were eliminated. Hence cost-saving of JPY9.5 billion (-5% of the current treatment flow) in total national expenditures would be expected. **Conclusion:** This study highlights that any policy decision-making for referral optimization to specialized care in appropriate epilepsy patients would be feasible with a cost-savings or very few budget impacts. However, important information in the decision-making such as transition probability to the next therapy or excuse for sensitive limitations is not available currently. Therefore, further research with reliable data such as big data analysis or a national survey with real-world treatment patterns is needed