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Purpose: There is a lack of real‐world data in Asian populations for brigatinib, a next‐generation anaplastic lymphoma kinase (ALK) inhibitor for patients with non‐small cell lung cancer (NSCLC). This study analysed real‐world outcomes and dosing patterns for brigatinib in patients with crizotinib‐refractory ALK+ NSCLC in South Korea. Methods: This retrospective, non‐interventional, cohort study used South Korean Health Insurance and Review Assessment claims data for adults with ALK+ NSCLC who initiated brigatinib between 19 April 2019 and 31 March 2021 after receiving prior crizotinib. Patients' characteristics, time to discontinuation (TTD), time to dose reduction, overall survival (OS) and treatment adherence were assessed. Results: The study included 174 patients (56.9% male; 27.0% with a history of brain metastases). Median duration of prior crizotinib was 17 (range 0.3–48) months. Median follow‐up after brigatinib initiation was 18 (range 0–34) months. Overall, 88.5% of patients received full‐dose brigatinib (180 mg/day) and 93.1% of patients were adherent (proportion of days covered ≥0.8). The median TTD was 24.9 months (95% CI 15.2–not reached). The probability of continuing treatment was 63.2% at 1 year and 51.5% at 2 years. The probability of continuing at full or peak dose was 79.7% at 1 year and 75.6% at 2 years. Median OS was not reached. The 2‐year OS rate was 68.7%. Conclusions: In this first nationwide retrospective study using national insurance claim data, brigatinib demonstrated real‐world clinical benefit as second‐line treatment after prior crizotinib in ALK+ NSCLC patients in South Korea. [ABSTRACT FROM AUTHOR]

We assessed the real-world effectiveness of cyclin-dependent kinase 4 and 6 (CDK4/6) inhibitors as first-line treatments in postmenopausal patients with HR+/HER2− advanced breast cancer, focusing on younger (<45 years) and older (>78 years) populations not considered in clinical trials. We analyzed nationwide claims data from the Health Insurance Review and Assessment Service between November 2016 and February 2021. In this retrospective cohort study, patients using CDK4/6 inhibitors and aromatase inhibitors were selected and grouped by age as follows: 45–78 years (trial-enrolled), <45 years (younger), and >78 years (older). We estimated the median real-world progression-free survival (rwPFS) and overall survival (OS) using the Kaplan-Meier method. We conducted Cox regression analysis using a sub-distribution hazard model to evaluate risk factors (age, history of prior systemic treatment, presence of metastasis, comorbidity index, and type of provider) and estimated hazard ratios (HR). Among the 2,830 patients who received CDK4/6 inhibitors as first-line therapy, we identified 358 (12.65%) younger and 148 (5.23%) older underrepresented patients. The younger patient group (50.84%) had the highest rate of prior systemic therapy, followed by the trial-enrolled (25.39%) and older patient groups (8.11%). The median rwPFS was shorter in the older group (19.30 months) than those in the younger and the trial-enrolled age groups (30.33 and 34.53 months, respectively; p =.002). The HR of older age for death was 1.59 (95% confidence interval (CI) = 1.24–2.03). For rwPFS, the HR of prior systemic therapy was 1.19 (95% CI = 1.04–1.37). The younger age group, which was underrepresented in the trial, did not show a significant difference in risk compared with the enrolled age group. However, the older age group, which was also underrepresented in the trial, faces a risk of mortality but not progression. Patients who fall outside the specified age groups for the clinical trial can still expect the same level of effectiveness in terms of progression. [ABSTRACT FROM AUTHOR]

Background: Amyotrophic lateral sclerosis (ALS) is a devastating disease which leads to loss of muscle function and paralysis. Historically, clinical drug development has been unsuccessful, but promising disease-modifying therapies (DMTs) may be on the horizon. Objectives: The aims of this study were to estimate survival, quality-adjusted life-years (QALYs) and costs under current care, and to explore the conditions under which new therapies might be considered cost effective. Methods: We developed a health economic model to evaluate the cost effectiveness of future ALS treatments from a UK National Health Service and Personal Social Services perspective over a lifetime horizon using data from the ALS-CarE study. Costs were valued at 2021/22 prices. Two hypothetical interventions were evaluated: a DMT which delays progression and mortality, and a symptomatic therapy which improves utility only. Sensitivity analysis was conducted to identify key drivers of cost effectiveness. Results: Starting from King's stage 2, patients receiving current care accrue an estimated 2.27 life-years, 0.75 QALYs and lifetime costs of £68,047. Assuming a 50% reduction in progression rates and a UK-converted estimate of the price of edaravone, the incremental cost-effectiveness ratio for a new DMT versus current care is likely to exceed £735,000 per QALY gained. Symptomatic therapies may be more likely to achieve acceptable levels of cost effectiveness. Conclusions: Regardless of efficacy, DMTs may struggle to demonstrate cost effectiveness, even at a low price. The cost effectiveness of DMTs is likely to be strongly influenced by drug price, the magnitude and durability of relative treatment effects, treatment starting/stopping rules and any additional utility benefits over current care. [ABSTRACT FROM AUTHOR]

Background & Aims: The cost‐effectiveness to screen hepatic fibrosis in at‐risk population as recommended by several professional societies has been limited. This study aimed to investigate the cost‐effectiveness of this screening strategy in the expanded at‐risk population recently proposed by several societies. Methods: A combined model of the decision tree and Markov models was developed to compare expected costs, quality‐adjusted life‐years (QALYs) and incremental cost‐effectiveness ratio (ICER) between screening and no screening groups. The model included liver disease‐related health states and cardiovascular disease (CVD) states as a base‐case analysis. Screening strategy consisted of fibrosis‐4 index (FIB‐4) followed by vibration‐controlled transient elastography (VCTE) and intensive lifestyle intervention (ILI) as a treatment for diagnosed patients. Results: Cost‐effectiveness analysis showed that screening the at‐risk population entailed $298 incremental costs and an additional 0.0199 QALY per patient compared to no screening (ICER $14 949/QALY). Screening was cost‐effective based on the implicit ICER threshold of $25 000/QALY in Korea. When the effects of ILI on CVD and extrahepatic malignancy were incorporated into the cost‐effectiveness model, the ICER decreased by 0.85 times from the base‐case analysis (ICER $12 749/QALY). In contrast, when only the effects of liver disease were considered in the model, excluding cardiovascular disease effects, ICER increased from the baseline case analysis to $16 305. Even when replacing with medical costs in Japan and U.S., it remained cost‐effective with the estimate below the countries' ICER threshold. Conclusions: Our study provides compelling evidence supporting the cost‐effectiveness of FIB‐4‐based screening the at‐risk population for advanced hepatic fibrosis. [ABSTRACT FROM AUTHOR]

Background: We aimed to examine whether patients with de novo and relapsed/progressed stage IIIB–IV non-small cell lung cancer (NSCLC) without epidermal growth factor receptor (EGFR) or anaplastic lymphoma kinase (ALK) mutations have different prognoses. Methods: This retrospective study analyzed the Health Insurance Review and Assessment claims data in South Korea from 2013 to 2020. Patients with stage IIIB–IV NSCLC without EGFR or ALK mutations who received first-line palliative therapy between 2015 and 2019 were identified. Overall survival (OS), time to first subsequent therapy (TFST), and time to second subsequent therapy (TSST) were estimated using the Kaplan–Meier method. Multivariate Cox regression analysis was used to reveal the impact of de novo versus relapsed/progressed disease on OS. Treatment patterns, including treatment sequence, top five most frequent regimens, and time to treatment discontinuation, were described in both groups. Results: Of 14,505 patients, 12,811 (88.3%) were de novo, and 1,694 (11.7%) were relapsed/progressed. The median OS in the de novo group was 11.0 versus 11.5 months in the relapsed/progressed group (P = 0.002). The ongoing treatment probability was higher in relapsed/progressed patients than in de novo patients from 6.4 months since the initiation of first-line treatment (P < 0.001). Median TSST was shorter in the de novo group than in the relapsed/progressed group (9.5 vs. 9.9 months, P < 0.001). In multivariate analysis, de novo disease was associated with shorter OS (hazard ratio 1.07; 95% confidence interval 1.01–1.14). The overall treatment patterns for de novo and relapsed/progressed patients were similar. Conclusions: De novo patients had poorer OS and TSST after the initiation of palliative therapy than relapsed/progressed patients. These findings suggest that the stage of the disease at the time of initial diagnosis should be considered in observational studies and clinical trials as a prognostic factor. [ABSTRACT FROM AUTHOR]

In South Korea, the ready-to-use hexavalent vaccine (against diphtheria, tetanus, pertussis, poliovirus, Haemophilus influenzae type b, and hepatitis B) is not listed despite its facility of no need to reconstitute. It, therefore, has the potential to augment the efficiency of prevention against the six infectious diseases, and it may reduce vaccine-related errors of reconstitution when compared with the currently used vaccination scheme of the pentavalent vaccine with the additional shots against hepatitis B. Given the assumed clinical equivalence between the two vaccination schemes, a cost-minimization analysis has been performed from a societal perspective including all the medical and non-medical direct and indirect costs when vaccinating one birth cohort. The results indicate that the ready-to-use hexavalent vaccine induces a cost reduction of KRW 47,155 (USD36.22) per infant or 12,026 million Korean Won ($9,236,417) in total for the whole birth cohort with 260,500 children. Using the ready-to-use hexavalent vaccine causes a lower infection rate, has fewer vaccination sessions, and may save much time as compared with the current vaccination scheme in place. The ready-to-use hexavalent vaccine may, therefore, benefit the National Immunization Program by reducing the total societal costs of vaccination while improving convenience of infants, parents, and medical care professionals. [ABSTRACT FROM AUTHOR]

Background: It is crucial that the safety profiles of biosimilars are similar to those of the original biologics. A better understanding of biosimilars and their relative safety and immunogenicity profiles are required for healthcare providers to prescribe them to patients with life-threatening cancer diseases who receive chemotherapies with potentially serious adverse events (AEs). Objectives: The purpose of this study was to collate and analyze currently available safety and immunogenicity outcomes of biosimilars used in oncology and compare their safety information with those of the original biologics. Methods: The MEDLINE and Cochrane Library databases were searched as at 28 February 2022. Four anti-cancer biosimilar molecules were considered: bevacizumab, trastuzumab, rituximab, and (peg)filgrastim. Through a systematic review, we selected the randomized controlled trials (RCTs) comparing safety outcomes between the biosimilars and original biologics of the four molecules. As safety outcomes, various treatment-emergent adverse events (TEAEs) were collated, such as any TEAE, serious AE, and TEAE higher than grade 3. A risk ratio (RR) per category of TEAE was estimated through a meta-analysis. A network meta-analysis (NMA) was also conducted to compare the safety among the biosimilar brands for TEAEs over 25% with higher variability in addition to the serious AE cases. Results: Forty-nine RCTs were identified. The results from the meta-analysis showed that the safety and immunogenicity profiles of all four biosimilar molecules are comparable with that of the original biologics at the TEAE level without statistically significant differences, except for diarrhea for (peg)filgrastim. The incidence of diarrhea with (peg)filgrastim was less than that with the original biologic (RR 0.66, 95% confidence interval 0.50–0.89). The NMA results showed similar safety profiles among the biosimilar brands for all four biosimilar molecules, except for the serious adverse event of a trastuzumab biosimilar (RR 0.296, 95% credible interval 0.109–0.840). Conclusion: The meta-analysis and NMA for all four biosimilars showed that the safety and immunogenicity profiles of biosimilar products in oncology are generally comparable with that of the original biologics at the TEAE level. However, additional evidence needs to be collected since several TEAEs of specific biosimilars were out of the equivalent range. The results of this study provide comparative safety information and a better understanding of oncology biosimilars for healthcare providers to prescribe them to patients. [ABSTRACT FROM AUTHOR]

In the early SARS-CoV-2 (COVID-19) pandemic, four major vaccines were approved despite limited efficacy and safety data through short regulatory review periods. Thus, it is necessary to assess the benefit-risk (BR) profiles of the COVID-19 vaccines. We conducted a quantitative BR assessment for four COVID-19 vaccines (mRNA-based: mRNA-1273 and BNT162b2; viral vector-based: Ad26.COV.2 and ChAdOx1-S) using multi-criteria decision analysis. Three benefit criteria and two risk criteria were considered: preventing COVID-19 infection for (1) adults aged ≥18 years; (2) seniors aged 60 years or older; and (3) severe COVID-19, adverse events (AEs), and serious AEs. Data were retrieved from clinical trials, observational studies, and county-specific AE monitoring reports. Based on the collected data, vaccines were scored for each criterion. 22 professionals weighted each criterion. The overall BR score was calculated using scores and weights. mRNA-1273 was the most preferred vaccine in pre-authorization and BNT162b2 in post-authorization. We found that the mRNA vaccine had a good balance between the benefits and risks. Using this BR assessment, the benefit-risk profile of COVID-19 vaccines can be updated with cumulated data. It will contribute to building evidence for decision making by policy makers and health professionals. [ABSTRACT FROM AUTHOR]

Background: Transthyretin cardiac amyloidosis, also known as transthyretin cardiomyopathy (ATTR-CM) is a poorly-recognized disease with delayed diagnosis and poor prognosis. This nationwide population-based study aimed to identify disease manifestations, economic burden, and mortality of patients with ATTR-CM.Methods: Data of newly diagnosed patients with ATTR-CM between 2013 and 2018 from the Korean National Health Insurance Service were used, covering the entire population. Patient characteristics included comorbidities, medical procedures, and medication. Healthcare resource utilization and medical costs were observed as measures of the economic burden. The Kaplan-Meier survival curve and years of potential life lost (YPLL) from the general population were estimated for disease burden with ATTR CM.Results: A total of 175 newly diagnosed patients with ATTR-CM were identified. The most common cardiac manifestation was hypertension (51.3%), while the most common non-cardiac manifestation was musculoskeletal disease (68.0%). Mean medical costs at the post-cohort entry date were significantly higher than those at the pre-cohort entry date ($1,864 vs. $400 per patient per month (PPPM), p < 0.001). Of the total medical costs during the study period, the proportion of inpatients cost was 12.9 times higher than the outpatients cost ($1,730 and $134 PPPM, respectively). The median survival time was 3.53 years from the first diagnosis of ATTR-CM, and the mean (SD) YPLL was 13.0 (7.7).Conclusions: Patients with ATTR-CM had short survival and high medical costs. To reduce the clinical and economic burdens, carefully examining manifestations of disease in patients can help with early diagnosis and treatment. [ABSTRACT FROM AUTHOR]

Background: Information on patient's death is a major outcome of health-related research, but it is not always available in claim-based databases. Herein, we suggested the operational definition of death as an optimal indicator of real death and aim to examine its validity and application in patients with cancer. Materials and methods: Data of newly diagnosed patients with cancer between 2006 and 2015 from the Korean National Health Insurance Service—National Sample Cohort data were used. Death indicators were operationally defined as follows: 1) in-hospital death (the result of treatment or disease diagnosis code from claims data), or 2) case wherein there are no claims within 365 days of the last claim. We estimated true-positive rates (TPR) and false-positive rates (FPR) for real death and operational definition of death in patients with high-, middle-, and low-mortality cancers. Kaplan−Meier survival curves and log-rank tests were conducted to determine whether real death and operational definition of death rates were consistent. Results: A total of 40,970 patients with cancer were recruited for this study. Among them, 12,604 patients were officially reported as dead. These patients were stratified into high- (lung, liver, and pancreatic), middle- (stomach, skin, and kidney), and low- (thyroid) mortality groups consisting of 6,626 (death: 4,287), 7,282 (1,858), and 6,316 (93) patients, respectively. The TPR was 97.08% and the FPR was 0.98% in the high mortality group. In the case of the middle and low mortality groups, the TPR (FPR) was 95.86% (1.77%) and 97.85% (0.58%), respectively. The overall TPR and FPR were 96.68 and 1.27%. There was no significant difference between the real and operational definition of death in the log-rank test for all types of cancers except for thyroid cancer. Conclusion: Defining deaths operationally using in-hospital death data and periods after the last claim is a robust alternative to identifying mortality in patients with cancer. This optimal indicator of death will promote research using claim-based data lacking death information. [ABSTRACT FROM AUTHOR]

Few studies assessed the association between major adverse cardiovascular events and adherence to warfarin and direct oral anticoagulants (DOACs) in patients with atrial fibrillation (AF). Therefore, we aimed to evaluate the effects of adherence to oral anticoagulants (OACs) in patients with AF using claims data (July 2014–April 2019). Using the initial 3-month medication possession rate (MPR), patients were categorized into adherent (MPR ≥ 0.8) or non-adherent (MPR < 0.8) groups. Propensity score matching of non-adherent group to adherent group was conducted for warfarin (1:1) and DOAC (1:3), respectively. Incidence of ischemic stroke, myocardial infarction (MI), intracranial hemorrhage, and all-cause death was assessed in the matched cohort (67,147 patients). The hazard ratio (HR) for adherence to OAC was estimated using the Cox proportional hazard model with adjusting covariate including age and sex. The risk for ischemic stroke, MI, and all-cause death was lower in the DOAC adherent group than in the DOAC non-adherent group (HR: 0.78; 95% confidence intervals: 0.73–0.84; 0.75, 0.60–0.94; 0.54, 0.51–0.57, respectively). Adherence to OAC was not associated with the risk of intracranial hemorrhage (1.01, 0.85–1.20). Commitment programs to improve adherence in patients with AF could maximize drug effectiveness and safety. [ABSTRACT FROM AUTHOR]

Background: The disease burden of active tuberculosis (TB) is considerable, but systematic reviews of economic evaluations of active TB treatments are scarce. Methods: PubMed, EMBASE, and the Cochrane Library databases were used to search for articles on cost-effectiveness analysis or cost-utility analysis that economically evaluated active TB treatments, which were then systematically reviewed by two independent reviewers. We extracted vital components of the included studies, such as country, population, intervention/comparator, primary outcome, values of outcomes, thresholds, model type, time horizon, and health states included in the model. Results: Seventeen studies were included in this systematic review. Thirteen dealt with interventions of medications, and the remaining four compared care strategies. The Markov model was the most commonly used tool to compare medications, whereas studies on care plans mainly used decision trees. The most commonly used primary outcome was disability-adjusted life years, followed by quality-adjusted life years. For treatment-naïve TB, the 4-month regimen was more cost-effective than the 6-month regimen mainly in low- and middle-income countries. For multidrug-resistant TB, a bedaquiline-based regimen was cost-effective. For multidrug-resistant TB, decentralized care that employed the use of home or mobile devices was more cost-effective than hospital-based centralized care in low- and middle-income countries. Conclusion: New treatment strategies to improve therapeutic outcomes by enhancing treatment adherence, such as regimens with shorter durations (2 or 4 months) and decentralized care, or new anti-TB agents (e.g., bedaquiline) have been suggested as cost-effective interventions for active TB. This review provides information on the economic evaluation of active TB from good-quality studies, thus aiding the future economic evaluation of active TB. [ABSTRACT FROM AUTHOR]

Background: Studies using data from randomized controlled trials (RCTs) and real-world data (RWD) have suggested that adjuvant cytokine-induced killer (CIK) cell immunotherapy after curative treatment for hepatocellular carcinoma (HCC) prolongs recurrence-free survival (RFS) and overall survival (OS). However, the cost-effectiveness of CIK cell immunotherapy as an adjuvant therapy for HCC compared to no adjuvant therapy is uncertain. Methods: We constructed a partitioned survival model to compare the expected costs, life-year (LY), and quality-adjusted life-year (QALY) of a hypothetical population of 10,000 patients between CIK cell immunotherapy and no adjuvant therapy groups. Patients with HCC aged 55 years who underwent a potentially curative treatment were simulated with the model over a 20-year time horizon, from a healthcare system perspective. To model the effectiveness, we used OS and RFS data from RCTs and RWD. We estimated the incremental cost-effectiveness ratios (ICERs) and performed extensive sensitivity analyses. Results: Based on the RCT data, the CIK cell immunotherapy incrementally incurred a cost of $61,813, 2.07 LYs, and 1.87 QALYs per patient compared to no adjuvant therapy, and the estimated ICER was $33,077/QALY. Being less than the willingness-to-pay threshold of $50,000/QALY, CIK cell immunotherapy was cost-effective. Using the RWD, the ICER was estimated as $25,107/QALY, which is lower than that obtained using RCT. The time horizon and cost of productivity loss were the most influential factors on the ICER. Conclusion: We showed that receiving adjuvant CIK cell immunotherapy was more cost-effective than no adjuvant therapy in patients with HCC who underwent a potentially curative treatment, attributed to prolonged survival, reduced recurrence of HCC, and better prognosis of recurrence. Receiving CIK cell immunotherapy may be more cost-effective in real-world clinical practice. [ABSTRACT FROM AUTHOR]

We aimed to determine the incidence of and identify the factors associated with treatment-resistant depression (TRD), psychiatric conditions, hospitalization, and cost in patients with major depressive disorder (MDD) who were treated using second-line strategies after an inadequate response to initial antidepressants (AD). Using South Korean National Health Insurance claims data (1 January 2013 to 30 June 2018), we conducted a retrospective cohort analysis in newly treated patients with MDD who subsequently switched or added AD, or added atypical antipsychotics (AAPs) as a second-line treatment. We assessed the incidence of treatment-resistant depression (TRD), psychiatric conditions, and hospitalization for the first 2 years and costs in the third year. Odds ratios (ORs) or relative ratios were estimated using logistic and linear regression models to identify the risk factors for clinical and economic outcomes. In 15,887 patients, the TRD was 16.81% during the 24-month follow-up period (14.14% in switching AD, 19.65% in adding AD, and 19.91% in adding AAP; p < 0.0001). When adding AD or AAP, the OR of TRD was 1.43 (95% confidence interval (CI): 1.30–1.56) and 1.42 (95% CI: 1.23–1.65), respectively, compared to switching AD. However, these factors were not associated with the incidence of psychiatric conditions. Adding AAP increased hospitalization (OR = 1.25, 95% CI: 1.11–1.41), the number of inpatient days by 2.57-fold (95% CI: 1.75–3.76), and cost by 1.20-fold (95% CI: 1.02–1.40), compared to switching AD; adding AD did not show a significant association with these outcomes. In patients with MDD with inadequate responses to initial AD, TRD still occurred after subsequent treatments according to clinical guidelines. Since the effectiveness of second treatment strategies can differ in reality, further analysis of the clinical and economic evidence regarding second treatment strategies, such as adding AD or AAP, is needed using real-world data. [ABSTRACT FROM AUTHOR]

Aims: We aimed to assess treatment persistence of tumor necrosis factor (TNF) inhibitors and non-TNF inhibitors in two groups of rheumatoid arthritis (RA) patients: biologic disease-modifying antirheumatic drug (bDMARD) initiators and switchers.Patients and methods: This retrospective cohort study utilized a national health insurance claims database. Patients aged ≥18 years initiating/switching bDMARD between 1 December 2013 and 31 December 2014, the index period, were followed for 12 months. Initiators who began treatment with a bDMARD during the index period were defined as having no bDMARD prescriptions for the previous year. Switchers who changed treatment from the previous bDMARD to the index bDMARD were defined as having different bDMARDs during the index period. Treatment persistence rates during the follow-up period were measured, and factors associated with non-persistence were assessed with the Cox proportional hazard model.Results: Of 2684 patients, treatment persistence rates were the highest for abatacept in initiators (69.3%) and tocilizumab in switchers (77.0%), while adalimumab showed the lowest persistence rates for both initiators and switchers (48.2%, 28.8%), followed by etanercept (51.3%, 41.0%). Adalimumab and etanercept were significantly more likely to show non-persistence (HR 1.58, 95% CI 1.27-1.96; HR 1.42, 95% CI 1.14-1.76) compared to infliximab for initiators, while tocilizumab was significantly more likely to show persistence (HR 0.411, 95% CI 0.206-0.819) in switchers.Conclusions: Non-TNF inhibitors showed higher persistence rates than TNF inhibitors in South Korean RA patients, and tocilizumab especially was associated with higher persistence in patients with inadequate response to TNF inhibitors. Good persistence with non-TNF inhibitors indicates the potential for long-term efficacy as first-line treatment. [ABSTRACT FROM AUTHOR]

Introduction: In order to look beyond the cost-effectiveness analysis, this study used a multi-criteria decision analysis (MCDA), which reflects societal values with regard to reimbursement decisions. This study aims to elicit societal preferences of the reimbursement decision criteria for anti cancer drugs from public and healthcare professionals.Methods: Eight criteria were defined based on a literature review and focus group sessions: disease severity, disease population size, pediatrics targets, unmet needs, innovation, clinical benefits, cost-effectiveness, and budget impacts. Using quota sampling and purposive sampling, 300 participants from the Korean public and 30 healthcare professionals were selected for the survey. Preferences were elicited using an analytic hierarchy process.Results: Both groups rated clinical benefits the highest, followed by cost-effectiveness and disease severity, but differed with regard to disease population size and unmet needs. Innovation was the least preferred criteria.Conclusions: Clinical benefits and other social values should be reflected appropriately with cost-effectiveness in healthcare coverage. MCDA can be used to assess decision priorities for complicated health policy decisions, including reimbursement decisions. It is a promising method for making logical and transparent drug reimbursement decisions that consider a broad range of factors, which are perceived as important by relevant stakeholders. [ABSTRACT FROM AUTHOR]

An experimental study was performed on the piston- and sloshing-mode moonpool resonances of offshore structures. Two different geometries were considered to investigate the flow characteristics in a plain moonpool and a moonpool with a cofferdam. To examine the efficiency of a cofferdam for reducing the flow in a moonpool, three cofferdam geometries were tested. The plain moonpool presented violent flows as a result of the piston- and sloshing-mode resonances. However, the moonpool with the cofferdam introduced violent sloshing waves instead of the ascent and descent of the water column in the piston-mode moonpool resonance. Among three different cofferdam geometries, the model with a right triangle facing to the left on the top of the cofferdam was most effective in reducing the flow in the moonpool when compared with the other models. [ABSTRACT FROM AUTHOR]

Purpose: The benefit-risk balance for drugs can alter post approval owing to additional data on efficacy or adverse events. This study developed a quantitative benefit-risk assessment (BRA) model for statins using multicriteria decision analysis with discrete choice experiments and compared a recent BRA with that at the time of approval.Patients and Methods: Following a systematic review of the literature, the benefit criteria within the statin BRA model were defined as a reduction in the plasma low-density lipoprotein cholesterol level and a reduction in myocardial infarction incidence; the risk criteria were hepatotoxicity (Liv) and fatal rhabdomyolysis (Rha). The scores for these criteria were estimated using mixed treatment comparison methods. Weighting was calculated from a discrete choice experiment involving 203 Korean patients. The scores and weights were integrated to produce an overall value representing the benefit-risk balance, and sensitivity analyses were conducted.Results: In this BRA model, low-density lipoprotein (relative importance [RI]: 37.50%) was found to be a more important benefit criterion than myocardial infarction (RI: 35.43%), and Liv (RI: 16.28%) was a more important risk criterion than Rha (RI: 10.79%). Patients preferred atorvastatin, and the preference ranking of cerivastatin and simvastatin was switched post approval because of the emergence of additional risk information related to cerivastatin.Conclusion: A quantitative statin BRA model confirmed that the preference ranking of statins changed post approval because of the identification of additional benefits or risks. [ABSTRACT FROM AUTHOR]

Molded flexible polyurethane (PU) foams were synthesized from a starch/petroleum based polyol, 2,4/2,6-toluene diisocyanate (TDI-80), using a one shot method with water as the blowing agent. The effects of chain extender type [starch (S series), diethanolamine (DEA, D series), glycerol (G series)] and content (0, 2, 5, 10 pphr) were extensively studied. The rate of foam formation, density, compression strength, glass transition temperature (Tg) and rubbery modulus of the foam increased with the addition and increasing content of extender. At the same extender content, DEA showed the highest of these properties, while starch showed the lowest. The rate of biodegradation in a buffer solution decreased with the addition of DEA and glycerol, due to the increased crosslinking density and hard segment content, but increased with starch, owing to its biodegradability. [ABSTRACT FROM AUTHOR]

Observability properties of errors in an integrated navigation system are studied with a control-theoretic approach in this paper. A navigation system with a low-grade inertial measurement unit and an accurate single-antenna Global Positioning System (GPS) measurement system is considered for observability analysis. Uncertainties in attitude, gyro bias, and GPS antenna Lever arm were shown to determine unobservable errors in the position, veIocity, and accelerometer bias. It was proved that all the errors can be made observable by maneuvering. Acceleration changes improve the estimates of attitude and gyro bias. Changes in angular velocity enhance the lever arm estimate. However, both the motions of translation and constant angular velocity have no influence on the estimation of the lever arm. A covariance simulation with an extended Kalman filter was performed to confirm the observability analysis. [ABSTRACT FROM AUTHOR]

Sloshing experiments have increasingly received academic attention. Understanding the measurement errors in the sloshing impact pressures is an important parts of the sloshing experiments since these errors, which arise from experimental conditions, affect the subsequent results. As part of the research on the sources of the measurement errors, focused on the effects of surface conditions of pressure sensors on the measurement of impact pressures. Thirty-six integrated circuit piezoelectric pressure sensors were placed on the upper surfaces of a two-dimensional tank to measure the sloshing impact pressures under surge or pitch motions. For each motion, the experimental conditions were divided in two based on whether the surfaces of the sensors were dry or wet. The peak pressures of each test were measured as twenty repeated experiments to ensure reliability. The flow in the tank was visualized using a high-speed camera to observe and analyze macroscopic and microscopic phenomena along the sensor surface. Thermal shock effects were confirmed by varying the experimental temperature and that of the sensor surface. The effects of the wet surface and droplets formed on the sensor surface on pressure measurements are discussed. [ABSTRACT FROM AUTHOR]