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

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.

Incidence of Hypophosphatemia After Intravenous Administration of Iron: A Matching-Adjusted Indirect Comparison of Data from Japanese Randomized Controlled Trials.

INTRODUCTION: Intravenous (IV) administration of iron is considered a safe and efficacious treatment for iron deficiency anemia (IDA), recommended in patients requiring rapid replenishment of iron, or intolerant or unresponsive to oral administration of iron. Recent randomized controlled trials (RCTs) have shown high incidence of hypophosphatemia after administration of two IV iron preparations: saccharated ferric oxide (SFO) and ferric carboxymaltose (FCM). The present study aimed to conduct matching-adjusted indirect comparison (MAIC) of hypophosphatemia incidence with these iron formulations and ferric derisomaltose (FDI) based on data from head-to-head RCTs conducted in Japan. METHODS: A MAIC of hypophosphatemia incidence was conducted on the basis of data from two head-to-head RCTs. The relative odds of hypophosphatemia with FDI versus SFO were obtained from patient-level data from a recent RCT and adjusted for cumulative iron dose, while parametric models of serum phosphate levels from a separate RCT were used to estimate the relative odds of hypophosphatemia with FCM with SFO. An anchored MAIC was then conducted comparing FDI with FCM. RESULTS: The adjusted odds of experiencing hypophosphatemia were significantly lower with FDI than SFO [odds ratio (OR) of 0.02; 95% confidence interval (CI) 0.01-0.05]. The parametric models of serum phosphate from the RCT comparing FCM with SFO provided an estimated OR of 1.17 for the incidence of hypophosphatemia with FCM versus SFO. Combining the two estimates in the MAIC showed that the odds of experiencing hypophosphatemia would be 52.5 (95% CI 27.7-99.4) times higher with FCM than FDI in patients with IDA associated with heavy menstrual bleeding in Japan. CONCLUSIONS: Direct comparison of patient-level data and a MAIC from two RCTs in Japanese patients with heavy menstrual bleeding indicated that hypophosphatemia is less frequent in patients treated with FDI than those with FCM or SFO. Results are in agreement with RCTs comparing FDI and FCM in patients with various etiologies conducted in the USA and Europe.

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.

Preferences for Rehabilitation in Persons with a History of Stroke: A Discrete Choice Experiment.

Objective: To investigate the preferences of persons with a history of stroke for various attributes of rehabilitation using a discrete choice experiment (DCE). Design: Cross-sectional study. Setting: A web-based survey. Participants: A total of 600 adults with a history of stroke who were not asked whether or not they had participated in previous rehabilitation. Intervention: None. Main Outcome Measures: Preference weights by attribute ie, treatment time (30 minutes, one hour, one and a half hours), treatment content (walking exercises, activities of daily living; ADL exercises), priority treatment of paralyzed limbs (upper extremity, lower upper extremity), treatment location (hospital visit, home visit), therapist gender, and out-of-pocket costs for stroke rehabilitation using discrete choice experiment. Results: The most common self-reported diagnosis was cerebral infarction (408 patients, 68%). The mean age was 62.0 ± 9.8 years, and 515 (85.8%) were male. Of the five attributes, excluding out-of-pocket costs, the highest relative importance score was treatment location (0.331), followed by treatment time (0.304). Among the rehabilitation programs, the statistically significant coefficients calculated were one hour of therapy (0.173, 95% CI = 0.088-0.258), hospital visits (0.241, 95% CI = 0.180-0.303), and female therapists (0.186, 95% CI = 0.125-0. 247). No significant differences were obtained regarding the treatment contents or the paralyzed limb to be treated. Conclusion: A discrete choice experiment revealed that persons with a history of stroke prefer a one-hour hospital rehabilitation program with a female therapist, with cost being a major consideration for rehabilitation. The results of this study may provide useful information for rehabilitation professionals.

Hygiene management of intermittent self-catheterization using reusable silicone catheters in people with spinal cord lesions: A cross-sectional Internet survey in Japan.

OBJECTIVES: To investigate hygiene management and catheter maintenance of reusable silicone catheters for intermittent self-catheterization (ISC) in Japan and examine their relationship with symptomatic urinary tract infection (sUTI). METHODS: We conducted a cross-sectional Internet survey of people performing ISC using reusable silicone catheters owing to spinal cord lesions in Japan. Hygiene management and catheter maintenance of reusable silicone catheters and the incidence and frequency of sUTI were evaluated. We also examined the significant risk factors for sUTI. RESULTS: Of 136 respondents, 62 (46%), 41 (30%), and 58 (43%) washed hands with water, washed hands with soap, and cleaned or disinfected the urethral meatus every time or most of the time before ISC, respectively. No significant difference was observed in the incidence and frequency of sUTI between respondents who adhered to these procedures and those who did not. There were no significant differences in the incidence and frequency of sUTI in respondents who changed their catheters every month and in those who changed their preservation solution within 2 days compared with those who did not. In multivariate analysis, pain during ISC, inconvenience of indoor mobility, bowel management problems, and participants' feeling of never having received instruction on catheter replacement were significant risk factors for sUTI. CONCLUSIONS: There are individual differences in hygiene management and catheter maintenance of reusable silicone catheters, but the influence of these differences on the incidence and frequency of sUTI is not clear. Pain during ISC, bowel management problems, and inadequate instruction on catheter maintenance procedures are factors associated with sUTI.

Evaluating process utilities for the treatment burden of chemotherapy in multiple myeloma in Japan: a time trade-off valuation study.

AIMS: This study estimated the "process utilities" of treatment options for patients with relapsed/refractory multiple myeloma (RRMM) in Japan using the time trade-off (TTO) method. Chimeric antigen receptor (CAR) T cell immunotherapy is available for patients with RRMM who are triple-class exposed (TCE) after treatment with immunomodulatory agents, proteasome inhibitors, and anti-CD38 monoclonal antibodies. However, the impact of available treatment options on health state utilities has not been well characterized, particularly in relation to process utilities. METHODS: Eight vignettes of health states and daily activity restrictions related to each of the following RRMM therapies were prepared: no treatment, CAR T cell therapy with idecabtagene vicleucel (ide-cel), regular intravenous infusion, and oral administration. A face-to-face survey of healthy Japanese adults who were representative of the general population was conducted. The TTO method was used to evaluate each vignette and to generate utility scores for each treatment regimen. RESULTS: Three hundred and nineteen respondents participated in the survey (mean age: 44 years [range: 20-64]; female: 50%). Utility scores for no treatment, ide-cel, oral pomalidomide, and dexamethasone (Pd) therapy ranged from ∼0.7 to 0.8. Utility scores for regular intravenous infusion regimens ranged from 0.50 to 0.56. There was a difference of ∼0.2 between the utility scores for no treatment/ide-cel/oral administration and regular intravenous infusions. CONCLUSIONS: Differences in treatment administration across RRMM therapies showed a substantial impact on health state utilities. When quantifying the value of treatments, process utility gains should be considered as an independent factor in health technology assessments.

Cost-effectiveness analysis of empagliflozin in patients with heart failure with reduced ejection fraction in Japan based on the EMPEROR-Reduced trial.

BACKGROUND: Several studies have reported the cost-effectiveness of sodium-glucose co-transporter 2 inhibitors in heart failure patients; however, their economic implications have not been sufficiently elucidated in Japan. METHODS: A Markov cohort model was developed to evaluate the cost-effectiveness of empagliflozin plus standard of care (SoC) vs. SoC for patients with heart failure with reduced ejection fraction (HFrEF) in Japan. Model inputs, including risk of clinical events, costs, and utilities based on Kansas City Cardiomyopathy Questionnaire Clinical Summary Scores were derived from EMPEROR-Reduced trial data, published literature, and a claims database. RESULTS: The model predicted lower lifetime hospitalizations for heart failure (HHFs) and additional quality-adjusted life-years (QALYs; 0.21) for empagliflozin plus SoC vs. SoC in the overall population. Increased costs of ¥100,495/patient ($772/patient), primarily driven by higher drug costs of ¥239,558/patient ($1,840/patient), were largely offset by reduced HHF management costs of -¥166,160/patient (-$1,276/patient), yielding an incremental cost-effectiveness ratio (ICER) of ¥469,672/QALY ($3,608/QALY). Results were consistent among subgroups and sensitivity analyses. In probabilistic sensitivity analysis, 82.5 % of runs were below the Japanese ICER reference value of ¥5,000,000/QALY ($38,408/QALY). CONCLUSIONS: Empagliflozin was demonstrated to be cost-effective for HFrEF patients in Japan based on the EMPEROR-Reduced trial data.

Health state utility estimation of Mycobacterium avium complex pulmonary disease using a time trade-off approach.

AIMS: To obtain appropriate health state utility values for cost-effectiveness analyses of new Mycobacterium avium complex pulmonary disease (MAC-PD) treatments. The impact of MAC-PD severity and symptoms on quality of life (QoL) also were quantified. METHODS: A questionnaire describing four health states, MAC-positive severe, MAC-positive moderate, MAC-positive mild, and MAC-negative, was developed based on St. George's Respiratory Questionnaire (SGRQ) Symptom and Activity scores from the CONVERT trial. The time trade-off (TTO) method with ping-pong titration procedure was used to estimate health state utilities. Regression analyses assessed the impacts of covariates. RESULTS: Of 319 Japanese adults (49.8% female, mean age 44.8 years), mean (95% CI) health state utility scores (MAC-positive severe, MAC-positive moderate, MAC-positive mild, and MAC-negative) were 0.252 (0.194-0.310), 0.535 (0.488-0.582), 0.816 (0.793-0.839), and 0.881 (0.866-0.896), respectively. MAC-negative state utility scores were significantly higher than MAC-positive severe (mean difference [95% CI], 0.629 [0.574-0.684]), MAC-positive moderate (0.346 [0.304-0.389]), and MAC-positive mild (0.065 [0.048-0.082]) scores (p < .001 each). Most participants would trade survival duration to avoid MAC-positive states (97.5% to avoid MAC-positive severe; 88.7% MAC-positive moderate; 61.4% MAC-positive mild). Regression analyses to investigate the impact of background characteristics showed similar utility differences between health states when not adjusted for covariates. LIMITATIONS: Some participant demographics differed from the general population; however, this did not impact utility differences among health states as regression analyses adjusting for demographics did not affect these differences. Similar investigations are needed among patients with MAC-PD and in other countries. CONCLUSIONS: This study evaluating the impact of MAC-PD on utilities using the TTO method demonstrates that differences in utilities are dependent on the severity of respiratory symptoms and their impacts on daily activities and QoL. These results could contribute to a better quantification of the value of MAC-PD treatments and improve assessments of cost-effectiveness.

Cross-sectional internet survey exploring symptomatic urinary tract infection by type of urinary catheter in persons with spinal cord lesion in Japan.

STUDY DESIGN: Cross-sectional study by members of patient advocacy groups. OBJECTIVES: To evaluate the incidence and frequency of symptomatic urinary tract infection (sUTI) in persons with spinal cord lesion (SCL) using different types of catheters based on an internet survey in Japan. SETTING: An internet survey. METHODS: We conducted an Internet survey of persons with SCL who were considered to be able to perform intermittent self-catheterization (ISC). We evaluated the incidence and frequency of sUTI over the last year in persons performing ISC and those managed by indwelling catheterization (IDC). We also compared the same parameters between persons in the ISC group using reusable silicone catheters and single-use catheters and those with and without a concomitant use of intermittent balloon catheters (i-IDC). RESULTS: Two-hundred and eighty-two persons were analyzed. In the ISC and IDC groups, sUTI occurred in 52.2% and 31.4% of persons (p = 0.021), respectively, in the last year, and the frequencies were 2.8 and 3.5 times a year (p = 0.127), respectively. There were no significant differences in the incidence or frequency of sUTI between persons using reusable catheters and single-use catheters or those with and without the concomitant use of i-IDC. CONCLUSIONS: sUTI occurred in about 1 in 2 persons with SCL performing ISC, which was significantly higher than in the IDC group, and the frequency of sUTI in persons performing ISC was about 3 times a year. The different types of catheters used for ISC were not associated with the incidence or frequency of sUTI. Sponsorship Coloplast Japan Inc.

Health state utility values for metastatic pancreatic cancer using a composite time trade-off based on the vignette-based approach in Japan.

BACKGROUNDS: Limited information is available on the utility values of metastatic pancreatic cancer, focusing on different health statuses, selected chemotherapy, and related grades 1/2 and 3/4 adverse events (AEs). We evaluated Japanese societal-based health-related utility values for metastatic pancreatic cancer by considering different grade toxicities commonly associated with chemotherapy using the vignette-based method. METHODS: We developed health status scenarios for patients with metastatic pancreatic cancer undergoing chemotherapy and conducted utility research using the developed scenarios in four steps: 'literature review,' 'exploratory interview,' 'content validation', and 'utility research'. In the development process, to consider the impact of AEs of chemotherapy for metastatic pancreatic cancer on health state utility values, we selected neutropenia, febrile neutropenia, diarrhea, nausea and vomiting, and neuropathy as representative AEs. Each AE was classified as either grade 1/2 or 3/4. We confirmed our created scenarios through cognitive interviews with the general population and clinical experts to validate the content. Finally, we developed 11 scenarios for using 'utility research,' evaluated in a societal-based valuation study using the face-to-face method. Participants for 'utility research' were the general population, and they evaluated these scenarios in the composite time trade-off (cTTO) and visual analog scale (VAS) of the European quality of life (EuroQol) valuation technology to derive health state utility scores. RESULTS: Of 220 responders who completed this survey, 201 were adapted into the analysis population. Stable disease with no AEs (reference state) had a mean utility value of 0.653 using cTTO. The lowest mean utility score in the stable state was 0.242 (stable disease + grade 3/4 vomiting). VAS results ranged from 0.189 to 0.468, depending on the various grades of AEs in stable disease. In addition, grade 3/4 AEs and grade 1/2 nausea/vomiting were associated with significantly greater disutility. Utility values were also strongly influenced by the direct impact of AE on physical symptoms, severity and their experience. In addition, 95.9% of the respondents agreed that they understood the questions in the post-response questionnaire. CONCLUSIONS: We clarified the health state utility values of patients with metastatic pancreatic cancer based on the general population in Japan. The effect on utilities should be considered not only for serious AEs, but also for minor AEs.

Developing a New Region-Specific Preference-Based Measure in East and Southeast Asia.

OBJECTIVES: Almost all preference-based measures (PBMs) have been developed in Western countries, with none having been formulated in Asian countries. In this study, we construct a new generic PBM based on concept elicitation using interview surveys in East and Southeast Asian countries and qualitative analysis. METHODS: This cross-sectional study included 225 adults recruited from 9 East and Southeast Asian countries or regions (Indonesia, Japan, Korea, mainland China, Malaysia, the Philippines, Singapore, Taiwan, and Thailand). Trained interviewers conducted semistructured interviews with 25 participants from the general population of each country/region. Qualitative data were analyzed using a content analysis approach. The selection of items was determined based on interview surveys and team member discussions. The description of items was considered based on a detailed qualitative analysis of the interview survey. RESULTS: A new region-specific PBM-the Asia PBM 7 dimensions instrument-was designed. It reflects East and Southeast Asian values and comprises 7 items: pain, mental health, energy, mobility, work/school, interpersonal interactions, and burden to others. CONCLUSIONS: The new region-specific instrument is one of the first PBMs developed in the context of non-Western countries. The Asia PBM 7 dimensions contains 7 items that address the core concepts of health-related quality of life that are deemed important based on East and Southeast Asian health concepts.

Indirect and Direct Mapping of the Cancer-Specific EORTC QLQ-C30 onto EQ-5D-5L Utility Scores.

OBJECTIVE: The aim of this study was to develop a response mapping algorithm to predict EQ-5D-5L utilities from European Organisation for Research and Treatment Quality of Life Questionnaire Core 30 (EORTC QLQ-C30) scores and compare performance with direct mapping approaches to identify the best performing algorithm. METHODS: The Multi-Instrument Comparison dataset contains responses to both the EQ-5D-5L and QLQ-C30 questionnaires from 692 individuals with a broad range of cancers. Response mapping was conducted, fitting ordered logistic regressions to predict response levels for each of the five EQ-5D dimensions and utilities were predicted using the US and Japanese EQ-5D-5L value sets to test the algorithm performance. Various direct mapping models were fitted: ordinary least squares, tobit, two-part (TPM), adjusted limited dependent variable mixture and beta mixture models. Model assessment and recommendations regarding the best mapping algorithm was based on goodness-of-fit statistics, predictive ability (measures of error, distribution of predicted utilities) and in sample cross-validation. RESULTS: The response mapping model performed well in terms of predictive ability and measurement error using the US or Japanese value set, with mean absolute error ranging from 0.0708 to 0.0988, and comparably to the TPM, which was the best performing direct algorithm. CONCLUSION: The developed mapping algorithms enable the prediction of EQ-5D-5L utilities from QLQ-C30 scores when EQ-5D-5L data have not been directly collected in clinical trials. The response mapping model offers the possibility of predicting EQ-5D-5L utility values using any national value set and can be generalised to multiple countries and oncology settings.

Apremilast Prolongs the Time to First Biologic Therapy in Japanese Patients with Psoriasis.

INTRODUCTION: Biologic agents are used in patients with severe psoriasis who have not adequately responded to existing conventional systemic therapies. However, only a limited number of medical institutions in Japan are approved to use them, and their relatively high cost represents a substantial burden to patients. Apremilast is an oral phosphodiesterase-4 inhibitor approved in Japan for the treatment of psoriasis vulgaris in adult patients with an inadequate response to topical therapies and psoriatic arthritis in adult patients with active disease. To date, a large-scale real-world study of treatment patterns and costs associated with apremilast in Japan has not been conducted. The objective of this study was to assess whether apremilast can prolong time to first biologic therapy use and decrease total medical cost. METHODS: Using the Medical Data Vision hospital-based claims database, 506 psoriasis patients were propensity score matched and analyzed (apremilast: n = 253; non-apremilast: n = 253). RESULTS: The incidence rate of first biologic therapy use per 1000 patient-years was significantly lower in the apremilast group than in the non-apremilast group (30.3 vs. 107.6; P < 0.001), and the total medical costs per month were significantly lower in the apremilast group than in the non-apremilast group (76,594 yen/month vs. 102,411 yen/month, P < 0.001). In a sensitivity analysis of a propensity-score-matched subset of eligible patients prescribed biologics during the follow-up period (apremilast: n = 14; non-apremilast: n = 14), the incidence of first biologic therapy use was 2,797.6 per 1000 patient-years (95% CI: 1,656.9, 4,723.6) in the non-apremilast group and 856.1 per 1000 patient-years (95% CI: 507.0, 1,445.5) in the apremilast group. CONCLUSION: These results suggest that apremilast prolongs the time to first biologic therapy use in patients with psoriasis, thereby reducing the total medical cost and decreasing the economic burden on patients.

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 ¥6 173 772. CONCLUSION: These results suggest that maintenance treatment with etanercept 25 mg is cost-effective.

Cost-effectiveness analysis of branded and authorized generic celecoxib for patients with chronic pain in Japan.

OBJECTIVES: The aim of this study was to examine the cost-effectiveness of branded and authorized generic (AG) celecoxib for chronic pain patients with osteoarthritis (OA), rheumatoid arthritis (RA), and low back pain (LBP), using real-world cost information for loxoprofen and pharmacotherapy for gastrointestinal bleeding. METHODS: This cost-effectiveness analysis was performed as a long-term simulation using the Markov model from the Japanese public healthcare payer's perspective. The analysis was conducted using loxoprofen with real-world weighted price by branded/generic distribution (hereinafter, loxoprofen with weighted price) as a comparator. In the model, we simulated the prognosis of patients with chronic pain by OA, RA, and LBP treated with loxoprofen or celecoxib, over a lifetime period. RESULTS: A cost-increase of 129,688 JPY (1,245.00 USD) for branded celecoxib and a cost-reduction of 6,268 JPY (60.17 USD) for AG celecoxib were recognized per patient in lifetime horizon, compared to loxoprofen with weighted price. No case was recognized to reverse the results of cost-saving by AG celecoxib in one-way sensitivity analysis. The incremental cost-effectiveness ratio of branded celecoxib attained 5,403,667 JPY/QALY (51,875.20 USD/QALY), compared to loxoprofen with the weighted price. CONCLUSION: The current cost-effectiveness analysis for AG celecoxib revealed its good value for costs, considering the patients' future risk of gastrointestinal injury; also, the impact on costs due to AG celecoxib against loxoprofen will be small. It implies that the disadvantage of AG celecoxib being slightly more expensive than generic loxoprofen could be offset by the good cost-effectiveness during the prognosis.

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.

Direct and Indirect Pathways for Health-Related Quality of Life Change from Pain Improvement in Neuropathic Pain Patients with Spine Diseases: Path Analysis with Structural Equation Modeling Using Non-Interventional Study Results of Pregabalin.

BACKGROUND: Chronic low back pain or chronic cervical pain often has a neuropathic pain (NeP) component and patients with these conditions complain of sleep deprivation, loss of physical function, and reduced productivity due to pain. The objective of this study was to clarify the pathway by which pain, sleep disturbance due to pain, and physical function status influence QOL measures in chronic low back pain patients with NeP associated with lumbar spine diseases (CLBP-NeP) and in chronic cervical pain patients with NeP associated with cervical spine diseases (CCP-NeP). METHODS: A model assuming pain numeric rating scale (NRS), pain-related sleep interference scale (PRSIS), and functional indices (Roland Morris Disability Questionnaire [RMDQ], Neck Disability index [NDI]) as factors that can affect outcomes such as QOL (calculated using EuroQoL 5 Dimensions (EQ-5D)), the Patient Global Impression of Change (PGIC), and the Clinical Global Impression of Change (CGIC) was developed using structural equation modeling. RESULTS: Overall trends were frequently observed in both patients with CLBP-NeP and CCP-NeP. Pain NRS had the largest comprehensive direct impact on QOL based on EQ-5D and an overall impression of changing symptoms. The effects of pain NRS on each outcome were largely due to direct pain-related effects; however, for EQ-5D, an indirect effect via functional improvement was the primary factor. CONCLUSION: Although the results of this study suggest that the indirect functional improvement of pain relief may not be recognized as a significant component of therapeutic effects by both physicians and patients, the pain-relieving intervention contributes directly to improvement of patients' overall QOL and also indirectly via functional improvement in Japanese primary care settings. Accordingly, to achieve the therapeutic goal for patients with NeP and minimize the impact of pain burden, our findings indicate that pain relief interventions are also crucial from the perspective of the patient's HRQOL.

Relationship Between the Number of Occlusal Supporting and Medical Cost: Analysis Using Large Claims Database from Employee Health Care Insurance in Japan.

BACKGROUND: There are several previous reports suggesting that the number of remaining teeth is related to increase of total medical expenditure. However, the measurements of oral healthcare conditions used in the previous studies were the number of remaining teeth, and occlusal support was not assessed. OBJECTIVES: The aim of this study was to evaluate the relationships between occlusal support and healthcare resource utilization. METHODS: This study was a retrospective cohort study using a claims database. Measurements of occlusal support were defined by the Eichner and Miyachi classification systems based on dental formula information. Medical healthcare resource usage was measured by medical visit rate and 12-month medical expenditure. RESULTS: Of the total population in the claims database, 1 288 713 patients were included in the analysis. The proportion of patients who had at least one medical visit and annual medical expenditure in the best condition classes in each classification measure (i.e. A1 for Eichner classification and Area I for Miyachi classification in both endpoints) were 58.2% and 61.1%, and JPY34 597 (US$314.52 at JPY110/US$) and JPY43 129 (US$392.08), respectively. Those in the poorest condition classes in each classification measure (i.e. B3 for Eichner classification and Area IV for Miyachi classification in the medical visit rate, and C1 for Eichner classification and Area III for Miyachi classification in medical expenditure) were 75.3% and 75.1%, and JPY149 339 (US$1357.63) and JPY120 925 (US$1099.32), respectively. We found a positive correlation with the outcomes by regression analysis adjusting for deterioration of occlusal support with age and gender. CONCLUSION: We found significant relationships between occlusal support conditions and healthcare resource utilization. The maintenance of oral health or dental treatment may positively impact overall health, and active dental intervention may reduce the total medical expenditure.

Re-challenge of Platinum-based Chemotherapy for Platinum-refractory Patients with Recurrent or Metastatic Head and Neck Cancer: Claims Data Analysis in Japan.

BACKGROUND: The role of platinum rechallenge in head and neck cancer (HNC) has not yet been fully evaluated. OBJECTIVES: It is our goal to assess the real-world treatment patterns and usefulness of platinum rechallenge in patients with platinum-refractory recurrent or metastatic HNC receiving platinum rechallenge. METHODS: This is a retrospective study using data from a Japanese hospital claims database stored in electronic hospital information systems. Patients with HNC or undefined histology with an HNC diagnosis using the disease code, between January 1, 2013 and September 30, 2016, were included. Patients diagnosed with other malignancies on or before the initial diagnosis of HNC and those without cancer stage information in the database were excluded from the study. RESULTS: A total of 43 994 patients were identified from the database as HNC patients. Of those, in patients who had cancer progression within 6 months after platinum-based chemotherapy administered for primary or recurrent disease (N=842), the median treatment duration of platinum rechallenge for platinum refractory patients was only 1 cycle. The second-line treatment continuation rate at 6 months was 20.1% for patients who received platinum rechallenges and 32.8% for those who received non-platinum-based regimens. CONCLUSIONS: The findings from this study of data from routine clinical practice suggest that the benefit of platinum rechallenge in a platinum-refractory setting would be limited.