Treatment patterns in metastatic bladder cancer in Japan: results of the CancerMPact® survey 2020.

Aim: To assess physician-reported treatment of metastatic bladder cancer in Japan. Methods: 76 physicians completed the CancerMPact® survey in July 2020, considering patients treated within 6 months. Results: Physicians treated a mean of 38.1 patients per month. Of cisplatin-eligible and -ineligible patients, 97.6 and 89.3%, respectively, received first-line platinum-based therapy, most commonly cisplatin plus gemcitabine (72.9%) and carboplatin plus gemcitabine (59.7%). 1.6 and 5.6% received first-line immune checkpoint inhibitors, respectively. 48.4 and 45.0%, respectively, progressed and received second-line therapy, most commonly with pembrolizumab (61.7%). Conclusion: In 2020, most patients with metastatic bladder cancer in Japan received first-line platinum-based chemotherapy; however, >50% received no subsequent treatment, highlighting the need for new treatment regimens to improve outcomes and maximize first-line treatment benefits.

In 2020, researchers surveyed 76 Japanese doctors who specialized in bladder and urinary system disorders about how they treated people with bladder cancer. Cisplatin, a type of chemotherapy drug, was the most common first treatment. For people who were unable to receive cisplatin, doctors often prescribed a similar chemotherapy drug called carboplatin. Just under half of the people received a second treatment for their cancer. New treatments are now available for bladder cancer, including the immunotherapy drug avelumab, which is given to people whose cancer stops growing or shrinks with their first chemotherapy treatment. More research is needed to better understand how bladder cancer is treated in Japan, including how new treatments are used.

Patient preferences for growth hormone treatment in Japanese children.

BACKGROUND: There are not clear evidence to date evaluating patients' and caregivers' preferences for the recombinant-human growth hormone (r-hGH) injection in children in Japan. This study aimed to quantitatively evaluated the factors driving preferences for daily r-hGH injections among Japanese children with growth hormone deficiency (GHD) or their caregivers and to determine the relative importance of treatment delivery factors. METHODS: This study was performed among Japanese children with GHD or their caregivers who visited a specialized clinic in Japan as part of their routine care. The participants were asked to complete a web-based discrete choice experiment (DCE) questionnaire. RESULTS: Choice-based conjoint analysis was used to evaluate the relative importance of the attributes of the choice predictors and determine utility scores for each attribute. Of the 47 respondents who participated in this study, 41 were caregivers who responded on behalf of the patients, the remaining six were patients who completed the DCE themselves. The injection schedule was found to be the most important factor for both patients and caregivers; a once-weekly injection schedule was preferred over a daily injection schedule. Storage and preparation was deemed more important to patients than it was to caregivers, with patients preferring storage at room temperature even if it required additional mixing (reconstitution). Both patients and caregivers showed a clear preference for devices that offered a dose-setting memory. CONCLUSIONS: A less frequent injection schedule may enhance adherence to r-hGH treatment and expected improve quality of life for GHD patients over the long term.

The first nationwide surveillance of antibacterial susceptibility patterns of pathogens isolated from skin and soft-tissue infections in dermatology departments in Japan.

To investigate the trends of antimicrobial resistance in pathogens isolated from skin and soft-tissue infections (SSTI) at dermatology departments in Japan, a Japanese surveillance committee conducted the first nationwide survey in 2013. Three main organisms were collected from SSTI at 30 dermatology departments in medical centers and 10 dermatology clinics. A total of 860 strains - 579 of Staphylococcus aureus, 240 of coagulase-negative Staphylococci, and 41 of Streptococcus pyogenes - were collected and shipped to a central laboratory for antimicrobial susceptibility testing. The patient profiles were also studied. Among all 579 strains of S. aureus, 141 (24.4%) were methicillin-resistant (MRSA). Among 97 Staphylococcus epidermidis strains, 54 (55.7%) were methicillin-resistant (MRSE). MRSA and MRSE were more frequently isolated from inpatients than from outpatients. Furthermore, these methicillin-resistant strains were also isolated more frequently from patients with histories of taking antibiotics within 4 weeks and hospitalization within 1 year compared to those without. However, there were no significant differences in MIC values and susceptibility patterns of the MRSA strains between patients with a history of hospitalization within 1 year and those without. Therefore, most of the isolated MRSA cases at dermatology departments are not healthcare-acquired, but community-acquired MRSA. S. pyogenes strains were susceptible to most antibiotics except macrolides. The information in this study is not only important in terms of local public health but will also contribute to an understanding of epidemic clones of pathogens from SSTI.

Burden of Antimicrobial Resistance in Japan: A Systematic Literature Review and Meta-Analysis.

INTRODUCTION: Antimicrobial resistance (AMR) is one of the most serious public health challenges worldwide, including in Japan. However, there is limited evidence assessing the AMR burden in Japan. Thus, this systematic literature review (SLR) and meta-analysis (MA) were conducted to assess the clinical and economic burden of AMR in Japan. METHODS: Comprehensive literature searches were performed on EMBASE, MEDLINE, the Cochrane Library, and ICHUSHI between 2012 and 2022 following the Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines. MA estimated a pooled effect between the two comparative arms (AMR vs. non-AMR). The results were reported in measures of odds ratios (ORs) for in-hospital mortality and in standardized mean differences (SMDs) for length of stay (LOS) and direct medical costs. RESULTS: Literature searches identified 1256 de-duplicated records, of which 56 observational studies (English, n = 35; Japanese, n = 21) were included. Of note, twenty-two studies (39.3%) compared the AMR group with non-AMR group. In the SLR, in-hospital mortality, LOS, and direct medical costs were higher in the AMR group compared to the non-AMR group. Eight studies were selected for the MA. In the AMR group, the pooled estimate showed a statistically higher in-hospital mortality [random effect (RE)-OR 2.25, 95% CI 1.34-3.79; I2 = 89%; τ2 = 0.2257, p < 0.01], LOS (RE-SMD 0.37, 95% CI - 0.09-0.84; I2 = 99%; τ2 = 0.3600, p < 0.01), and direct medical cost (RE-SMD 0.53, 95% CI 0.43-0.62; I2 = 0.0%; τ2 = 0.0, p = 0.88) versus the non-AMR group. CONCLUSION: Our study presents an overview of the clinical and economic burden of AMR in Japan. Patients with AMR infections experience significantly higher in-hospital mortality, LOS, and direct medical costs compared with patients without AMR infections.

Cost-effectiveness analysis of abrocitinib compared with standard of care in adult moderate-to-severe atopic dermatitis in Japan.

Atopic dermatitis (AD) is a chronic inflammatory skin disease with a significant clinical, economic, and human burden. The JAK1 Atopic Dermatitis Efficacy and Safety (JADE) program's Phase 3 trials demonstrated that as a treatment for moderate-to-severe AD in adults with previous exposure to immunotherapy, abrocitinib showed superior efficacy and safety compared with standard of care (SoC), consisting of topical corticosteroids. This study assessed the cost-effectiveness of abrocitinib with SoC versus SoC alone for this patient population in Japan from a societal perspective. A hybrid decision tree and Markov model were used to capture the initial treatment and long-term maintenance phases. Clinical inputs at 16 weeks were obtained through a Bayesian network meta-analysis of four pivotal trials from the JADE program. Clinical inputs at 52 weeks were derived from the JADE EXTEND trial. Response-specific utility inputs were obtained from published literature. Resource use, costs, and productivity inputs were gathered from Japanese claims analysis, literature, public documents, and expert opinion. Costs and quality-adjusted life years (QALYs) were discounted at 2.0% per year and incremental cost-effectiveness ratios (ICERs) were calculated. Sensitivity and scenario analyses were performed to validate the base case results and explore a payer perspective. Over a lifetime horizon and with the base-case societal perspective, abrocitinib produced a mean gain of 0.75 QALYs, incremental costs of JPY (¥) 2 270 386 (USD [$] 17 265.6), and a resulting ICER of ¥3 034 514 ($23 076.5) per QALY compared with SoC. From a payer perspective, the incremental costs increased to ¥4 476 777 ($34 044.4), with an ICER of ¥5 983 495 ($45 502.6) per QALY. The results were most sensitive to treatment-specific, response-based utility weights, drug costs, and productivity-related inputs. From a Japanese societal perspective, abrocitinib demonstrated superior QALYs and with a willingness-to-pay threshold of ¥5 000 000 ($38 023.4) per QALY, can be considered cost-effective compared with SoC as a treatment for moderate-to-severe AD in adult patients with previous immunosuppressant exposure.

Economic burden of alopecia areata: A study of direct and indirect cost in Japan using real-world data.

Alopecia area (AA) is a common autoimmune disorder, characterized by hair loss. Although its impact on quality of life is fairly well understood, studies on the economic impact of AA are limited. The aim of this study was to quantify the personal and nationwide economic burden of AA in Japan. Data were drawn from the Adelphi AA Disease Specific Programme (DSP)™, a real-world, cross-sectional survey with retrospective data collection, of Japanese physicians and patients with AA. The study was conducted in 2021, before the approval of Janus kinase inhibitors for AA. Physicians and their consulting AA patients completed questionnaires regarding disease severity, treatment, and AA-related costs. The Work Productivity and Activity Impairment questionnaire was used to evaluate the impact of AA on patients' work and activity. Nationwide estimates of cost and productivity loss were extrapolated from collected patient data. A total of 50 physicians provided data on 235 patients; 58.7% were female, mean ± SD age was 41.1 ± 11.8 years, and mean physician-estimated scalp hair loss was 40.4% ± 30.2%. Prescription medication use was high (92.3% of patients), but the use of over-the-counter medication was low, at 8.7%. Mean cost to patients for medication was ¥ 4263 (US$ 32.42) per month. Productivity while at work (presenteeism) was significantly impaired (23.9% ± 25.7%), but absenteeism was low (0.9% ± 2.8%). The total nationwide cost of AA was estimated at 112.7 billion yen (US$ 857 million), of which 88.1 billion yen (78.2%) was due to productivity loss. Over 2 million days per year of activity time were estimated to be lost due to AA. Thus, despite not being a physically limiting disease, AA has a significant impact in terms of cost and time, both on a personal and national level. These data highlight the need for more targeted interventions to reduce the effects of AA on the Japanese economy.

Estimating the Economic and Clinical Value of Introducing Ceftazidime/Avibactam into Antimicrobial Practice in Japan: A Dynamic Modelling Study.

BACKGROUND: Antimicrobial resistance (AMR) is one of the most serious public health challenges worldwide, including in Japan. Globally, research and development of new antimicrobials has stalled due to unfavorable market conditions, which undervalue antimicrobials. Furthermore, Japan faces the additional challenge of delayed commercialization for a number of recently approved treatments. OBJECTIVE: This study aims to examine the impact on AMR of introducing a new anti-infective treatment, ceftazidime/avibactam, into current treatment strategies. It reports the resulting clinical and economic outcomes from the perspective of healthcare payers in Japan. METHODS: A previously published and validated dynamic disease transmission model was adapted to the Japanese setting. The model estimated health economic outcomes for treating three Gram-negative hospital-acquired infections, under different treatment strategies, from a healthcare payers' perspective. Outcomes were assessed over a 10-year time horizon with a willingness-to-pay threshold of ¥5,000,000 (US$45,556) per quality-adjusted life-year (QALY) gained and an annual discount rate of 2% applied to costs and benefits. RESULTS: Introducing ceftazidime/avibactam in the framework of a diversification strategy with piperacillin/tazobactam is associated with reducing 798,640 bed days, equating to ¥21.0 billion (US$190.9 million) savings in hospitalization costs, and a gain of 363,034 life-years, or 308,641 QALYs. This translates into a monetary benefit of ¥1.56 trillion (US$14.3 billion) to Japanese healthcare payers. DISCUSSION: Introducing a new antimicrobial agent into clinical practice is associated with considerable clinical and economic benefits. This analysis demonstrates that the approach taken to incorporate a new antimicrobial agent into clinical practice impacts on the scale of these clinical and economic benefits; greater benefits are associated with earlier use of antimicrobials as part of an antimicrobial stewardship program. CONCLUSION: This analysis shows that changing the way in which a new antimicrobial is used within a treatment strategy has the potential for additional significant clinical and economic value.

Cost-Effectiveness Analysis of Tofacitinib Compared with Biologics in Biologic-Naïve Patients with Moderate-to-Severe Ulcerative Colitis in Japan.

OBJECTIVE: Tofacitinib is an oral Janus kinase inhibitor approved for the treatment of ulcerative colitis (UC). The objective of this study was to evaluate the long-term cost-effectiveness of tofacitinib versus current biologics, considering combinations of first-line (1L) and second-line (2L) therapies, from a Japanese payer's perspective in patients with moderate-to-severe active UC following an inadequate response to conventional therapy and in those who were naïve to biologics. METHODS: A cost-effectiveness analysis was conducted during the time horizon specified in the Markov model, which considers a patient's lifetime as 60 years and an annual discount rate of 2% on costs and effects. The model compared tofacitinib with vedolizumab, infliximab, adalimumab, golimumab, and ustekinumab. The time of active treatment was divided into induction and maintenance phases. Patients not responding to their biologic treatment after induction or during the maintenance phase were switched to a subsequent line of therapy. Treatment response and remission probabilities (for induction and maintenance phases) were obtained through a systematic literature review and a network meta-analysis that employed a multinomial analysis with fixed effects. Patient characteristics were sourced from the OCTAVE Induction trials. Mean utilities associated with UC health states and adverse events (AEs) were obtained from published sources. Direct medical costs related to drug acquisition, administration, surgery, patient management, and AEs were derived from the JMDC database analysis, which corresponded with the medical procedure fees from 2021. The drug prices were adjusted to April 2021. Further validation through all processes by clinical experts in Japan was conducted to fit the costs to real-world practices. Scenario and sensitivity analyses were also performed to confirm the accuracy and robustness of the base-case results. RESULTS: In the base-case, the treatment pattern including 1L tofacitinib was more cost-effective than vedolizumab, infliximab, golimumab, and ustekinumab for 1L therapies in terms of cost per quality-adjusted life year (QALY) gained (based on the Japanese threshold of 5,000,000 yen/QALY [38,023 United States dollars {USD}/QALY]). The base-case results demonstrated that the incremental costs would be reduced for all biologics, and decreases in incremental QALYs were observed for all biologics other than adalimumab. The incremental cost-effectiveness ratio (ICER) was found to be dominant for adalimumab; for the other biologics, it was found to be less costly and less efficacious. The efficiency frontier on the cost-effectiveness plane indicated that tofacitinib-infliximab and infliximab-tofacitinib were more cost-effective than the other treatment patterns. When infliximab-tofacitinib was compared with tofacitinib-infliximab, the ICER was 282,609,856 yen/QALY (2,149,157 USD/QALY) and the net monetary benefit (NMB) was -12,741,342 yen (-96,894 USD) with a threshold of 5,000,000 yen (38,023 USD) in Japan. Therefore, infliximab-tofacitinib was not acceptable by this threshold, and tofacitinib-infliximab was the cost-effective treatment pattern. CONCLUSION: The current analysis suggests that the treatment pattern including 1L tofacitinib is a cost-effective alternative to the biologics for patients with moderate-to-severe UC from a Japanese payer's perspective.

An Economic Evaluation Estimating the Clinical and Economic Burden of Increased Vancomycin-Resistant Enterococcus faecium Infection Incidence in Japan.

INTRODUCTION: While incidence rates of vancomycin-resistant Enterococcus faecium have remained comparatively low in Japan, there have been increasing reports of more vancomycin-resistant Enterococcus (VRE) outbreaks, requiring costly measures to contain. Increased incidence of VRE in Japan may lead to more frequent and harder to contain outbreaks with current control measures, causing a significant burden to the healthcare system in Japan. This study aimed to demonstrate the clinical and economic burden of vancomycin-resistant E. faecium infections to the Japanese healthcare system and the impact of increasing rates of vancomycin resistance. METHODS: A de novo deterministic analytic model was developed to assess the health economic outcomes of treating hospital-acquired VRE infections; patients are treated according to a two-line treatment strategy, dependent on their resistance status. The model considers hospitalisation costs and the additional cost of infection control. Scenarios investigated the current burden of VRE infections and the additional burden of increased incidence of VRE. Outcomes were assessed over a 1-year and 10-year time horizon from a healthcare payer's perspective in a Japanese setting. Quality-adjusted life years (QALYs) were valued with a willingness-to-pay threshold of ¥5,000,000 ($38,023), and costs and benefits were discounted at a rate of 2%. RESULTS: Current VRE incidence levels in enterococcal infections in Japan equates to ¥130,209,933,636 ($996,204,669) in associated costs and a loss of 185,361 life years (LYs) and 165,934 QALYs over 10 years. A three-fold increase (1.83%) is associated with an additional ¥4,745,059,504 ($36,084,651) in total costs on top of the current cost burden as well as an additional loss of 683 LYs over a lifetime, corresponding to 616 QALYs lost. CONCLUSION: Despite low incidence rates, VRE infections already represent a substantial economic burden to the Japanese healthcare system. The substantial increase in costs associated with a higher incidence of VRE infections could result in a significant economic challenge for Japan.

Health-related quality of life in patients with alopecia areata: Results of a Japanese survey with norm-based comparisons.

Alopecia areata (AA) is a non-scarring hair loss disorder affecting approximately 2% of the global population. AA is reported to have a significant negative impact on the emotional and psychological well-being of the patients. This study aimed to evaluate the health-related quality of life (HRQoL) of Japanese patients with AA in comparison to the Japanese population norms (national standard values for Japanese) using Short Form Health Survey 36 Item Version 2.0 (SF-36v2). The study also aimed to access the negative effect of AA on patients' daily lives and the proportion of patients having anxiety and/or depression. This cross-sectional, non-interventional web-based survey study included 400 participants aged 17-84 years currently suffering from medically diagnosed AA. The assessment tools integrated in the online questionnaire included SF-36v2, the Dermatology Life Quality Index (DLQI), and the Hospital Anxiety and Depression Scale (HADS). All outcome measures from the tools were evaluated across the study population. SF-36v2 subscale scores for patients with AA revealed lower scores specifically for mental health (45.7 ± 10.1 points), social functioning (45.8 ± 10.9 points), vitality (46.2 ± 9.8 points), and role emotional (46.9 ± 11.6 points) as compared to the Japanese population norms of 50 ± 10 points each. The DLQI questionnaire-based analysis indicated that 32.1% of respondents showed a moderate to extremely large effect on their lives; and HADS-A (anxiety) and HADS-D (depression) scores categorized 46.0% and 41.8% respondents as doubtful-to-definite cases, respectively. Multivariate linear regression revealed that hair loss range, age, comorbidities, and depression significantly worsened DLQI scores. In conclusion, the results of this survey demonstrated that a significant decrease in the HRQoL scores was observed in Japanese patients with AA in comparison with the national norms. Hence, emphasis on mental health is crucial for AA management.

Systematic Literature Review of the Use of Productivity Losses/Gains in Cost-Effectiveness Analyses of Immune-Mediated Disorders.

INTRODUCTION: In light of the lack of an agreed international standard for how to conduct cost-effectiveness analyses (CEAs), including cost-utility analyses (CUAs) from a societal perspective, there is uncertainty regarding to what extent the inclusion of productivity losses/gains in economic evaluations can affect cost-effectiveness results and subsequently decisions on whether to recommend new health technologies. To investigate this, we conducted a systematic review of CEAs and CUAs of drug-based therapies for a set of chronic immune-mediated disorders to understand how cost elements and calculation methods related to productivity losses/gains are used, examine the impact on the incremental cost-effectiveness ratio (ICER) of including productivity costs, and explore factors that affect the inclusion of productivity loss. METHODS: Databases (MEDLINE® In-process, MEDLINE, Embase and Cochrane Library) were searched from January 2010 to October 2020 by two independent reviewers for all CEAs and CUAs in adults with any of the following conditions: ankylosing spondylitis, chronic idiopathic urticaria, Crohn's disease, fibromyalgia, juvenile idiopathic arthritis, psoriasis, rheumatoid arthritis, systemic lupus erythematosus and ulcerative colitis. Relevant study data were extracted and evidence was synthesized for both qualitative and quantitative analysis. Productivity cost elements including absenteeism, presenteeism, unemployment/early retirement, premature mortality and informal care were extracted, along with the method used to determine them. A multivariate analysis was performed to identify factors associated with the inclusion of productivity loss. RESULTS: Our searches identified 5016 records, culminating in 198 unique studies from 234 publications following screening. Most of the studies investigated rheumatoid arthritis (37.0%) or psoriasis (32.0%). The majority were CUAs, with some including both a CEA and a CUA (73.0%). Most studies used a payer perspective only (28.5%) or a societal perspective only (21.0%). Of the 49 studies incorporating productivity losses/gains, 42 reported the type of cost element used; all of these used patient absenteeism, either alone or in addition with other elements. Only 16 studies reported the method used to value productivity changes, of which eight used a human capital approach, four used a friction cost approach and four used both approaches. Twenty-eight of the 49 studies (57.1%) reported inclusion of productivity losses/gains as contributing to more favourable cost-effectiveness outcomes and ICERs, while 12 (24.5%) reported no substantial impact. On the basis of a multivariate analysis, rheumatoid arthritis as the target disease had a statistically significant association with the inclusion of productivity loss compared with psoriasis and inflammatory bowel disease. CONCLUSIONS: The results of our review suggest that incorporating productivity cost elements may positively affect cost-effectiveness outcomes in evaluations of therapeutics for immune-mediated disorders. Our work highlights the continued need for clarity when reporting how CEAs and CUAs in this disease area are conducted, in order to better inform healthcare decision-making.

Cost-Effectiveness Analysis of the Treatment Strategies with or without Opioid Medications in Surgery-Eligible Patients with Osteoarthritis in Japan.

AIM: The aim of this study was to evaluate the cost effectiveness of treatment strategies without opioid medications (non-opioid treatment strategy) versus strategies with opioid medications (opioid treatment strategy) among surgery-eligible patients with osteoarthritis (OA) of the knee or hip in Japan. MATERIALS AND METHODS: We built a Markov cohort model to evaluate outcomes for the treatment strategies in surgery-eligible patients aged ≥ 65 years with OA of the knee or hip in Japan. The opioid treatment strategy as an intervention includes a health state with opioid medication in the treatment pathway. On the other hand, for the non-opioid treatment strategy, there is no health state with opioid medication. A targeted literature review and database analysis were conducted to identify and define the values of the variables included in the model. The time horizon was set to 30 years, and a 2% discount was applied for cost and quality-adjusted life-years (QALYs). Sensitivity analysis and scenario analysis were performed in the model. The outcomes were QALYs and the incremental cost-effectiveness ratio (ICER). RESULTS: In the base-case analysis, the non-opioid treatment strategy was dominant over the opioid treatment strategy and associated with an incremental cost and QALYs of - 53,878 JPY (- 499 USD) and 0.03 QALYs, respectively, in patients with knee OA, and - 54,129 JPY (- 502 USD) and 0.02 QALYs, respectively, in patients with hip OA. One-way sensitivity analysis showed the ICER was most sensitive to the QALY for opioid monotherapy. Probabilistic sensitivity analyses showed a high degree of uncertainty associated with the results. LIMITATIONS: Study limitations included assumptions related to transition probabilities of the health states, and a lack of Japanese-specific data for transition probabilities, incidence of adverse events and utility values. CONCLUSIONS: This study suggests that the non-opioid treatment strategy is cost effective compared with the opioid treatment strategy in the management of surgery-eligible patients with OA of the knee or hip. However, this final conclusion may not be accurate as the methodology is heavily reliant on assumptions.

A Systematic Literature Review of Economic Evaluations and Cost Studies of the Treatment of Psoriasis, Atopic Dermatitis, and Chronic Urticaria.

INTRODUCTION: Psoriasis (PSO), atopic dermatitis (AD), and chronic urticaria (CU) are common manifestations of immunological skin and subcutaneous conditions and have been shown to have a substantial impact on the quality of life of patients. The cost of treating those conditions can also be high, as the use of biologic treatments has become more common for moderate to severe patients. In this review, we examine characteristics of economic evaluations and cost studies conducted for the three conditions. METHODS: A literature search was conducted using PubMed, Embase, and the Cochrane Library from January 1, 2016 to October 26, 2020 to identify economic evaluations where the cost of one or more drug treatment was evaluated and cost studies covering any intervention type. Each database was searched using keyword and MeSH terms related to treatment costs (e.g., health care cost, drug cost, etc.) and each condition (e.g., PSO, AD, eczema, CU, etc.). RESULTS: A total of 123 studies were reviewed, including 104 studies (85%) of PSO (including psoriasis, plaque psoriasis, psoriatic arthritis, and psoriasis vulgaris), 14 studies (11%) of AD, and 5 studies (4%) of CU. Seventy-two studies (59%) reviewed reported the inclusion of biologic treatments, 10 studies (8%) did not include biologic treatments, and 41 studies (33%) did not report whether or not a biologic treatment was included. While nearly all studies (98%) included direct costs, only 22 studies (18%) included indirect costs. CONCLUSIONS: Economic evaluations for AD and CU may be needed in order to better understand the value of new treatments. Moreover, a clearer delineation for biologic treatments and indirect costs (i.e., productivity losses and gains) may be required.

Use of Productivity Loss/Gain in Cost-Effectiveness Analyses for Drugs: A Systematic Review.

BACKGROUND: Inclusion of productivity losses and gains in cost-effectiveness analyses for drugs is recommended by pharmacoeconomic guidelines in some countries and is considered optional in others. Often guidelines recommend analysis based on the payer perspective, but suggest that a supplemental analysis based on the societal perspective may be submitted that includes productivity losses/gains. However, there is no universally recognized framework for the approach to including productivity losses and gains in pharmacoeconomic analyses. OBJECTIVES: This study aimed to systematically review literature on cost-effectiveness analyses of drug interventions that included costs associated with productivity losses/gains and to summarize the types cost elements included and cost calculation methods employed. Moreover, this study examines variations in the calculation of productivity losses/gains by target disease type, geographic region, income group, period of analysis, and analysis time horizon-as well as the impact of their inclusion on the study outcomes. METHODS: A search of three databases was performed, including MEDLINE, Embase, and the Cochrane Library, to identify cost-effectiveness and cost-utility analyses that included indirect costs such as productivity losses/gains. Publications from January 2010 to October 2019 were examined and selected for inclusion by two independent reviewers. In addition to the citation details, data on the country of analysis, country income group, target disease area, study sponsorship, type of analysis, study design, time horizon, analysis perspective, productivity loss/gain elements included, the approach used to estimate productivity losses/gains, and the impact of their inclusion on the study outcome-namely the incremental cost effectiveness ratio-were extracted and summarized. RESULTS: The search strategy identified 5038 unique studies, and 208 were included in the final analysis. Among the studies reviewed, 165 (79%) were conducted in high-income countries and 160 (77%) were conducted for North American and European/Central Asian countries. The productivity loss/gain elements included in the analysis were reported for 169 studies (81%). Absenteeism only was included for 98 studies (47%), and absenteeism plus presenteeism was included for 29 studies (14%). Absenteeism plus some other element such as costs associated with unemployment and/or early retirement was included for 32 studies (15%) examined. Only one out of four of the studies reviewed included information on the approach used to estimate productivity losses/gains, which was predominantly the human capital approach. One-hundred forty-four studies (69%) reported the impact of including productivity losses/gains on the ICER, with 110 studies (53%) reporting that their inclusion contributed to more favorable cost-effectiveness. CONCLUSIONS: Although inclusion of productivity losses/gains was shown to have a favorable impact on evaluations for many studies, their impact and method of calculation was often not reported or was unclear. Further examination and discussion is needed to consider the optimal framework for considering productivity losses/gains in cost-effectiveness analyses, including the appropriate cost elements to include (e.g., patient absenteeism, caregiver absenteeism, presenteeism, unemployment, etc.) and how those costs should be estimated.

Productivity loss/gain in cost-effectiveness analyses for vaccines: a systematic review.

Introduction: The kinds of costs included in cost-effectiveness analyses (CEAs) for vaccines, such as direct medical costs and indirect costs, may affect their outcomes. While some guidelines recommend inclusion of costs associated with productivity losses/gains, very little guidance is provided about the productivity elements to include and their calculation approach.Areas covered: We conducted a systematic review of CEAs for vaccines and vaccine programs published between 1 January 2010 and 19 November 2019 that included productivity costs using Medline, Embase, and the Cochrane Library. The kind of productivity elements included their calculation approach, and the impact of their inclusion on cost-effectiveness are summarized. Among 88 studies identified, productivity elements included were reported for 71 studies (81%) with absenteeism being the most commonly included element. Only 24 studies (27%) reported the approach used to calculate productivity costs (human capital vs. friction approach). Most studies (81%) reported a more favorable cost-effectiveness with the inclusion of productivity losses/gains.Expert opinion: Inclusion of productivity losses/gains for CEAs for vaccines has resulted in more favorable cost-effectiveness based on the studies reviewed. However, clearer guidance on the productivity elements to include by disease area and more transparency on the calculation method used may be needed.

Investigation of Factors Considered by Health Technology Assessment Agencies in Eight Countries.

BACKGROUND: Health technology assessment (HTA) organizations play a crucial role in optimizing healthcare resources, but the factors influencing decision making vary by country. OBJECTIVE: HTAs of cancer and hepatitis C drugs were evaluated across developed countries to understand differences in decision processes and criteria. METHODS: The HTA organizations evaluated are from France, Germany, Italy, Spain, the United Kingdom (UK), Australia, Canada and Japan. Economic evaluation types and 28 factors in the following categories were evaluated: clinical uncertainties/issues; disease/population/treatment consideration factors including National Institute for Health and Care Excellence's (NICE) special circumstances factors (e.g. end-of-life and innovation); and International Society for Pharmacoeconomics and Outcomes Research (ISPOR) additional value elements. Qualitative and correspondence analyses were conducted to assess the differences across organizations. RESULTS: Incremental cost-effectiveness ratio (ICER) using quality-adjusted life-year (QALY) was evaluated in Canada, the UK, Australia and Japan. The highest observed clinical uncertainties were clinical benefits and comparator. For cancer drugs, correspondence analysis showed France, Australia, Canada and the UK to have common attributes observed, such as unmet needs and stakeholder persuasion. In addition, the UK reported end-of-life, issues around current treatment and innovation, whereas Germany reported manageable/insignificant adverse events more frequently. Finally, fear of contagion, equity and scientific spillover value elements were only observed in Australia. CONCLUSION: Although clinical factors play a predominant role in the decision to reimburse medicine, HTA organizations consider additional aspects as well. If the methodology of HTA was clearly outlined, there would be more transparency in HTA systems leading to better understanding amongst stakeholders about decision making.

Estimating the Economic and Clinical Value of Reducing Antimicrobial Resistance to Three Gram-negative Pathogens in Japan.

Background: Antimicrobial resistance (AMR) represents a significant global public health crisis. Despite ample availability of Gram-positive antibiotics, there is a distinct lack of agents against Gram-negative pathogens, including carbapenem-resistant Enterobacterales, which remains a real threat in Japan. The AMR Action Plans aim to mitigate the growing public health concern posed by AMR. Objective: This study aims to estimate the clinical and economic outcomes of drug-resistant Gram-negative pathogens forecasts for Japan to guide resource allocation defined within the upcoming National AMR Action Plan. Methods: A previously published and validated dynamic health economic model was adapted to the Japanese setting. The model used a 10-year time horizon with a willingness-to-pay threshold of ¥5 000 000 (US $46 827) and discounting was applied at a rate of 2% to costs and benefits. Clinical and economic outcomes were assessed as a function of varying AMR levels of three Gram-negative pathogens in Japan by up to 100% of the current level. Results: Reducing drug-resistant Gram-negative pathogens in Japan has the potential to save 4 249 096 life years, corresponding to 3 602 311 quality-adjusted life years. The associated maximum clinical and economic gains were estimated at up to 4 422 284 bed days saved, up to 3 645 480 defined daily doses of antibiotics avoided, up to ¥117.6 billion (US $1.1 billion) saved in hospitalization costs, and a net monetary benefit of up to ¥18.1 trillion (US $169.8 billion). Discussion: Learnings from this study can be used by the Japanese government to help inform decision-making on the strategies that may be included in the upcoming National AMR Action Plan and facilitate allocation of the required budget. Conclusions: This analysis demonstrated the considerable economic and clinical value of reducing AMR levels of three Gram-negative pathogens in Japan and could be utilized to support the valuation of antimicrobial treatment and resistance in Japan and more broadly.

Treatment procedures and associated medical costs of methicillin-resistant Staphylococcus aureus infection in Japan: A retrospective analysis using a database of Japanese employment-based health insurance.

OBJECTIVES: This study aimed to determine the patient characteristics, treatment procedures, and medical costs of methicillin-resistant Staphylococcus aureus infections in clinical practice in Japan. METHODS: Using the MinaCare database of healthcare information covering nearly 3 million individuals, of which 90% were aged 20-59 years, we extracted and analyzed data of patients who were aged ⩾15 years and diagnosed with methicillin-resistant S. aureus during hospitalization between April 2010 and August 2015. RESULTS: A total of 684 patients with methicillin-resistant S. aureus infection were listed in the database, of which 365 were eligible to be included in this study. Mean patient age was 52.9 years, and 31.5% of the patients were females. Methicillin-resistant S. aureus bacteremia was the most common methicillin-resistant S. aureus infection (32.9%) with a mean age of 48.5 years, followed by pneumonia (24.1%) with a mean age of 61.0 years and methicillin-resistant S. aureus surgical site infection (6.3%) with a mean age of 49.7 years. Vancomycin was the most frequently prescribed anti-methicillin-resistant S. aureus drug used as the first-line therapy (68.5%), followed by teicoplanin (14.2%), linezolid (7.9%), arbekacin (5.8%), and daptomycin (3.6%). The mortality rate was 11.0%, and the mean treatment duration was 13.3 days. The median total medical cost per patient was US$5083. The median treatment cost for methicillin-resistant S. aureus bacteremia was the highest among the methicillin-resistant S. aureus infections at US$9099, followed by methicillin-resistant S. aureus pneumonia at US$3676 and surgery site infections at US$2084. CONCLUSION: Although the proportion of patients with methicillin-resistant S. aureus is very small in the employment-based health insurance database, methicillin-resistant S. aureus bacteremia is the most common methicillin-resistant S. aureus infection in the working-age population and requires the highest medical cost. Methicillin-resistant S. aureus pneumonia is more common in the elderly and is a cause of high mortality.

Behavior of natural estrogens in semicontinuous activated sludge biodegradation reactors.

Biological degradation of natural estrogens was investigated by separately spiking 17 beta-estradiol (E2) and estrone (E1) into activated sludge reactors operated in a semi-continuous flow mode under aerobic conditions. By conducting runs for simultaneous addition of glucose over the designated initial concentrations of 0, 10, 30, 50 and 100 mg l(-1), respectively, the likely effect of the easily biodegradable organic constituent on the degradation rate of the natural estrogens was also studied. The spiked E2 disappeared in a manner much faster than E1; and its disappearance occurred through elimination of its metabolic byproduct of E1. The apparent first-order disappearance rate of E2 and E1 fell in the ranges of 0.84-4.31h(-1) and 0.15-0.84 h(-1), respectively when spiked separately into respective reactors. A general trend of decreases in the disappearance rate with increases of the initial glucose concentration was revealed. The presence of glucose was also found capable of lowering the conversion ratio from E2 to E1.