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Home medication review (HMR) programs could minimise patients' health-related costs and burdens, thereby enhancing the quality of life and well-being. The aim of this economic evaluation is to determine if home medication review by community pharmacists (HMR-CP) for patients with type 2 diabetes mellitus (T2DM) is a cost-effective intervention from the Malaysian healthcare provider perspective.The economic evaluation was conducted alongside the randomised controlled trial (RCT) to estimate the intermediate cost-effectiveness of HMR-CP for patients with T2DM. A Markov model was then constructed to project the lifetime cost-effectiveness data beyond the RCT. The primary outcomes for the economic evaluation were HbAThe intervention and health services costs throughout the 6-month HMR-CP trial were RM121.45 (USD28.64) [95%CI: RM115.89 to 127.08 (USD27.33-29.97)] per participant. At a 6-month follow-up, a significant reduction in HbAHMR-CP was a cost-effective intervention that had significantly reduced the HbA

To assess the correlation between PFS2 and OS among patients with advanced prostate cancer (PC) in a real-world setting for Japan. This was a retrospective analysis using the Japanese MDV database. Patients with nmCRPC (non-metastatic Castration-Resistant PC), mCRPC (metastatic Castration-Resistant PC), and mCNPC (metastatic Castration-Naïve PC) were identified and their medical records were investigated for PFS2 and death. Association between PFS2 and OS was determined using the Pearson’s, Spearman’s, Kendall's Tau, and Fleischers’ correlation coefficients. A total of 386,484 patients with PC were identified from the database, of which, 1,783 patients with nmCRPC, 630 with mCRPC, and 454 with mCNPC met the predefined eligibility criteria. Significant correlation between PFS2 and OS was observed in patients with nmCRPC (Pearson’s r = 0.873; 95% CI: 0.849 – 0.897, Spearman’s r = 0.909; 95% CI: 0.893 – 0.925; Kendall’s Tau r = 0.831; 95% CI: 0.812 – 0.850, Fleischers’ r = 0.682; 95% CI: 0.601 – 0.764), mCRPC (Pearson’s r = 0.812; 95% CI: 0.758 – 0.865, Spearman’s r = 0.895; 95% CI: 0.868 – 0.923, Kendall’s Tau r = 0.789; 95% CI: 0.755 – 0.823, Fleischers’ r= 0.439; 95% CI: 0.334 – 0.544), and mCNPC (Pearson’s r = 0.931; 95% CI: 0.899 – 0.964, Spearman’s r = 0.943; 95% CI: 0.922 – 0.964, Kendall’s Tau r = 0.866; 95% CI: 0.836 – 0.896, Fleischers’ r = 0.756; 95% CI: 0.624 – 0.888). The results of this study indicate a significant correlation between PFS2 and OS, which adds additional evidence to the existing literature of using PFS2 as a surrogate endpoint for OS in patients with PC.

Background and purpose: Several recent randomized controlled trials (RCTs) in non-metastatic castration resistant prostate cancer (nmCRPC) have demonstrated a significant improvement in metastasis-...

Very few data are available to demonstrate the economic benefit of early paliperidone palmitate once-monthly long-acting injectable (PP1M) treatment in patients with schizophrenia or schizoaffective disorder.This study has retrospectively compared the healthcare utilization and associated costs of pre- and post-PPIM treatment in 413 patients with schizophrenia or schizoaffective disorder recruited from three major public hospitals providing psychiatric services in Hong Kong. Patients were categorized into early treatment (≤3 years since diagnosis) and chronic (3 years) groups, and also whether they were receiving polypharmacy (POP).It was found that patients who were started on early therapy with no POP had the most favourable outcomes. Overall results of the entire cohort, including both early and late treatments, indicate that there was a slight increase in annual in-patient days (IP) per patient and outpatient visit (OP) by 3.18 and 1.87, respectively, and a decrease in emergency room visit (ER) of 0.9 (p 0.05). For non-polypharmacy (NP) patients receiving early PP1M therapy, there was a significant decrease in IP and ER of 21.56 (p 0.05) and 1.15 (p 0.05), respectively, but an increase in OP of 1.88 (p 0.05). For patients with POP, there was an all-across increase in IP and all-across decrease in OP and ER. In monetary terms, a NP patient receiving early therapy may have an overall saving of HKD40,878 (USD5,241, 1USD = 7.8HKD) per year compared to HKD6,224 (USD798) in patients where therapy was given after 3 years. For patients with POP, there was an all-across increase in overall spending despite reductions in OP and ER.From the 413 patients studied, potential annual savings is higher by early administration of PPIM in patients with NP. Analysis using multivariate linear regression based on generalized estimating equations and sensitivity analysis using a linear mixed model supported the findings.

Purpose To assess the comparative efficacy of short-acting muscarinic antagonists (SAMAs), long-acting muscarinic antagonists (LAMAs), LAMA in combination with long-acting beta-agonists (LABAs; LAMA/LABAs) and inhaled corticosteroids (ICS) in combination with LABA (ICS/LABAs) for the maintenance treatment of COPD. Materials and methods We systematically reviewed 74 randomized controlled trials (74,832 participants) published up to 15 November 2017, which compared any of the interventions (SAMA [ipratropium], LAMA [aclidinium, glycopyrronium, tiotropium, umeclidinium], LAMA/LABA [aclidinium/formoterol, indacaterol/glycopyrronium, tiotropium/olodaterol, umeclidinium/vilanterol] and ICS/LABA [fluticasone/vilanterol, budesonide/formoterol, salmeterol/fluticasone]) with each other or with placebo. A random-effects network meta-analysis combining direct and indirect evidence was conducted to examine the change from baseline in trough FEV1, transition dyspnea index, St George's Respiratory Questionnaire and frequency of adverse events at weeks 12 and 24. Results Inconsistency models were not statistically significant for all outcomes. LAMAs, LAMA/LABAs and ICS/LABAs led to a significantly greater improvement in trough FEV1 compared with placebo and SAMA monotherapy at weeks 12 and 24. All LAMA/LABAs, except aclidinium/formoterol, were statistically significantly better than LAMA monotherapy and ICS/LABAs in improving trough FEV1. Among the LAMAs, umeclidinium showed statistically significant improvement in trough FEV1 at week 12 compared to tiotropium and glycopyrronium, but the results were not clinically significant. LAMA/LABAs had the highest probabilities of being ranked the best agents in FEV1 improvement. Similar trends were observed for the transition dyspnea index and St George's Respiratory Questionnaire outcomes. There were no significant differences in the incidences of adverse events among all treatment options. Conclusion LAMA/LABA showed the greatest improvement in trough FEV1 at weeks 12 and 24 compared with the other inhaled drug classes, while SAMA showed the least improvement. There were no significant differences among the LAMAs and LAMA/LABAs within their respective classes.

Background To evaluate nasal carriage, antibiotic susceptibility and molecular characteristics of methicillin-resistant Staphylococcus aureus (MRSA), as well as the risk factors of MRSA colonization, in human immunodeficiency virus (HIV)-infected patients in northern Taiwan. Methods From September 2014 to November 2015, HIV-infected patients seeking outpatient care at four hospitals were eligible for this study. A nasal specimen was obtained from each subject for the detection of S. aureus and a questionnaire was completed by each subject. MRSA isolates once identified were characterized. Results Of 553 patients surveyed, methicillin-susceptible S. aureus (MSSA) was detected in 119 subjects (21.5%) and MRSA in 19 subjects (3.4%). Female gender, injection drug use, smoking, hepatitis C virus carrier, cancer and antibiotic use within 1 year were positively associated with MRSA colonization. By multivariate analysis, only cancer (adjust odds ratio (aOR) 7.78, [95% confidence interval (CI), 1.909–31.731]) and antibiotic use within 1 year (aOR 3.89, [95% CI, 1.219–12.433]) were significantly associated with MRSA colonization. Ten isolates were characterized as sequence type (ST) 59/staphylococcal chromosome cassette (SCC) IV or VT, endemic community strains in Taiwan, four isolates as ST 8/SCCmec IV (USA 300) and one isolate as ST 239/SCCmec IIIA, a hospital strain. All the community-associated MRSA isolates were susceptible to trimethoprim-sulfamethoxazole (TMP-SMX). Conclusions Nasal MRSA carriage in HIV-infected patients seeking outpatient care was low (3.4%) in northern Taiwan. Most of the colonizing isolates were genetically endemic community strains and exhibited high susceptibility to TMP-SMX and fluoroquinolones. Cancer and antibiotic use within 1 year were associated with MRSA colonization.

A systematic review and network-meta analysis (NMA) were performed to test significance of the galactagogue effect of fenugreek administrated to lactating women versus other comparators (i.e., placebo/control/other galactagogues). A pairwise comparison for the treatment effect was carried out to generate the forest plot for the NMA. League tables were generated using treatment effect, weighted mean difference (WMD; 95% confidence interval, CI) for all pairwise comparisons, where WMD > 0 favors the column-defining treatment. Five studies were identified with 122 participants receiving treatment with fenugreek. The NMA results of 4 studies indicated that consumption of fenugreek significantly increased amount of the produced breast milk [11.11, CI 95% 6.77, 15.46] versus placebo. The pairwise comparison revealed that fenugreek was effective as a galactagogue compared to placebo, control, and reference groups WMD 17.79 [CI 11.71, 23.88]. However, the effect of fenugreek was substantially inferior to Coleus amboinicus Lour and palm date. The NMA using pairwise comparison demonstrated the effect of C. amboinicus and palm date in the stimulation of the breast milk production was comparable and superior to all comparators.

The majority of the carbamazepine-induced Stevens-Johnson syndrome and toxic epidermal necrolysis CBZ-SJS/TEN are associated with HLA-B*15:02 in Asian populations where this allele is common. In contrast, the association with HLA-A*31:01 is only reported in Japanese and Europeans. This study aimed to further investigate the association with HLA-A*31:01 besides HLA-B*15:02 in a multiethnic Malaysian population. Twenty-eight CBZ-SJS/TEN cases and 227 CBZ-tolerant controls were recruited. Association was tested by comparing carrier frequencies of the alleles between cases and controls. Significant associations were detected between HLA-B*15:02 and CBZ-SJS/TEN in independent ethnic groups: Malays [P=2.00×10; odds ratio (OR): 49.0; 95% confidence interval (CI): 9.36-256.81], Chinese (P=0.0047; OR: 14.3; 95% CI: 2.38-86.03) and Indians (P=0.04; OR: 13.8; 95% CI: 1.51-124.99). Combined analysis of all ethnic groups showed a significant association with OR Cochran-Mantel-Haenszel (ORCMH) of 26.6 (95% CI: 12.80-55.25; PCMH=2.31×10). In Indians, HLA-A*31:01 was found to be associated significantly with CBZ-SJS/TEN (P=0.023; OR: 10.4; 95% CI: 1.64-65.79) and combined analyses of both variants, HLA-A*31:01 and HLA-B*15:02, increased the strength of the association (P=0.0068; OR: 14.3; 95% CI: 2.20-92.9). Besides HLA-B*15:02, our study found a new association between HLA-A*31:01 and CBZ-SJS/TEN in Indians.

Objective: The value of cochlear implantation (CI) has not been established in Taiwan. The purpose of this study was to evaluate the cost-effectiveness of paediatric CI within the context of Taiwan's national health insurance (NHI) programme.Design: A Markov model-based cost-utility analysis (CUA) was conducted to evaluate the cost-effectiveness of a unilateral CI (UCI) with a contralateral acoustic hearing aid (UCI-HA) compared with a bilateral HA. We performed one-way sensitivity analyses to identify the cost variables that affected the incremental cost-effectiveness ratio (ICER) the most. Monte Carlo simulation was used to explore the simultaneous effect of all uncertain parameters on cost-effectiveness.Study sample: Not applicable.Results: Compared with bilateral HAs, the ICER for UCI-HA was $6487 per quality-adjusted life year (QALY) gained. The ICERs were consistently below $7000 per QALY gained and were most sensitive to the selling price of the external CI device. When this selling price increased by 10%, the ICER of UCI-HA would increase to $6954 per QALY gained. UCI-HA has a probability greater than 50% of being cost-effective if the cost-effectiveness threshold exceeds approximately $10,000 per QALY.Conclusions: Our analysis suggested that within the context of Taiwan's NHI programme, UCI is highly cost-effective for deaf children.

ObjectivesThis study was conducted to evaluate the cost-effectiveness of sunitinib versus interferon-alfa for the treatment of advanced and/or metastatic renal cell carcinoma (RCC) in Singapore.MethodsA partitioned survival model with three health states (progression-free, progressive disease, and death) was developed from a healthcare payer perspective over a 10-year time horizon. Survival curves from the pivotal trial of sunitinib versus interferon-alfa were extrapolated beyond the trial period to estimate the underlying progression-free survival and overall survival parametric distributions. Health state utilities were derived from the literature and direct costs were sourced from local public healthcare institutions. The sunitinib dose in the model reflected local prescribing practices whereby a combination of 50 mg (28 percent) and 37.5 mg (72 percent) strengths are used.ResultsThe base-case analysis comparing sunitinib versus interferon-alfa resulted in an incremental cost effectiveness ratio (ICER) of SGD191,061 (USD139,757) per quality-adjusted life-year gained. Sensitivity analysis demonstrated that the ICER was most sensitive to variations in the utility value assumed for the progression-free health state and the price of sunitinib.ConclusionsIn the absence of any price reduction, sunitinib had an exceedingly high ICER and was not considered a cost-effective use of healthcare resources in Singapore's context for the first-line treatment of advanced RCC. The findings from our evaluation will be useful to inform local healthcare decision making and resource allocations for tyrosine kinase inhibitors when appraised alongside comparative clinical effectiveness data and payer affordability considerations.

A cochlear implant is a small electronic device that provides a sense of sound for the user, which can be used unilaterally or bilaterally. Although there is advocacy for the benefits of binaural hearing, the high cost of cochlear implant raises the question of whether its additional benefits over the use of an acoustic hearing aid in the contralateral ear outweigh its costs. This cost-effectiveness analysis aimed to separately assess the cost-effectiveness of simultaneous and sequential bilateral cochlear implantations compared to bimodal hearing (use of unilateral cochlear implant combined with an acoustic hearing aid in the contralateral ear) in children with severe-to-profound sensorineural hearing loss in both ears from the Singapore healthcare payer perspective. Incremental quality-adjusted life year (QALYs) gained and costs associated with bilateral cochlear implants over the lifetime horizon were estimated based on a four-state Markov model. The analysis results showed that, at the 2017 mean cost, compared to bimodal hearing, patients receiving bilateral cochlear implants experienced more QALYs but incurred higher costs, resulting in an incremental cost-effectiveness ratio (ICER) of USD$60,607 per QALY gained for simultaneous bilateral cochlear implantation, and USD$81,782 per QALY gained for sequential bilateral cochlear implantation. The cost-effectiveness of bilateral cochlear implants is most sensitive to utility gain associated with second cochlear implant, and cost of bilateral cochlear implants. ICERs increased when the utility gain from bilateral cochlear implants decreased; ICERs exceeded USD$120,000 per QALY gained when the utility gain was halved from 0.03 to 0.015 in both simultaneous and sequential bilateral cochlear implantations. The choice of incremental utility gain associated with the second cochlear implant is an area of considerable uncertainty.

Objectives To systematically review and assess the quality of the economic evidence of adjuvant trastuzumab usage in early breast cancer in Asian countries. Methods Literature search was performed using 6 electronic databases (PubMed, Scopus, Ovid MEDLINE, EconLit, National Health Service Economic Evaluation Database, and ISI Web of Knowledge). The final search was performed in October 2018. All potential economic studies were then checked for eligibility. The reporting and methodological qualities of each study were independently assessed by 2 authors of this review, using the Consolidated Health Economic Evaluation Reporting Standards, Drummond, and Philips checklists. To compare the different currencies used in these studies, all costs were converted into US dollars (2016). Results A total of 6 studies were included; most of them were performed from the healthcare provider perspective. The incremental cost-effectiveness ratio for evaluation performed for a lifetime horizon were reported at $8573 and $20 816 per quality-adjusted life-year in 2 studies. The model outcome was generally sensitive to the changes in trastuzumab drug acquisition cost and discount rate, as well as its clinical effectiveness. For the quality assessment, all studies fulfilled more than 50% of the requirements in the Consolidated Health Economic Evaluation Reporting Standards, Drummond, and Philips checklists. Conclusions Adjuvant trastuzumab therapy is considered a cost-effective option for early breast cancer in Asian countries including China, Iran, Japan, Singapore, and Taiwan. All studies were generally well conducted. Economic evaluations from the societal perspective, with inclusion of indirect and informal care costs, are warranted to facilitate informed decision making among policy makers.

Although pneumococcal conjugate vaccines (PCVs) have been available for prevention of invasive pneumococcal disease (IPD) caused by Streptococcus pneumoniae (S. pneumoniae) for over a decade, their adoption into national immunization programmes in low- and middle-income countries (LMICs) is still limited. Economic evaluations (EEs) play a crucial role in support of evidence-informed decisions. This systematic review aims to provide a critical summary of EEs of PCVs and identify key drivers of EE findings in LMICs. We searched Scopus, ISI Web of Science, PubMed, Embase and Cochrane Central from their inception to 30 September 2015 and limited the search to LMICs. The search was undertaken using the search strings ‘pneumococc* AND conjugat* AND (vaccin* OR immun*)’ AND ‘economic OR cost-effectiveness OR cost-benefit OR cost-utility OR cost-effectiveness OR cost-benefit OR cost-utility’ in the abstract, title or keyword fields. To be included, each study had to be a full EE of a PCV and conducted for an LMIC. Studies were extracted and reviewed by two authors. The review involved standard extraction of the study overview or the characteristics of the study, key drivers or parameters of the EE, assumptions behind the analyses and major areas of uncertainty. Out of 134 records identified, 22 articles were included. Seven studies used a Markov model for analysis, while 15 studies used a decision-tree analytic model. Eighteen studies performed a cost-utility analysis (CUA), with disability-adjusted life-years, quality-adjusted life-years or life-years gained as a measure of health outcome, while four studies focused only on cost-effectiveness analysis (CEA). Both CEA and CUA findings were provided by eight studies. Herd effects and serotype replacement were considered in 10 and 13 studies, respectively. The current evidence shows that both the 10-valent and 13-valent PCVs are probably cost effective in comparison with the 7-valent PCV or no vaccination. The most influential parameters were vaccine efficacy and coverage (in 16 of 22 studies), vaccine price (in 13 of 22 studies), disease incidence (in 11 of 22 studies), mortality from IPD and pneumonia (in 8 of 22 studies) and herd effects (in 4 of 22 studies). The findings were found to be supportive of the products owned by the manufacturers. Our review demonstrated that an infant PCV programme was a cost-effective intervention in most LMICs (in 20 of 22 studies included). The results were sensitive to vaccine efficacy, price, burden of disease and sponsorship. Decision makers should consider EE findings and affordability before adoption of PCVs.

Intravenous immunoglobulin (IVIG) has been recommended for steroid-resistant chronic inflammatory demyelinating polyradiculoneuropathy (CIDP). The treatment, however, is very costly to healthcare system, and there remains no evidence of its economic justifiability. This study aimed to conduct an economic evaluation (EE) of IVIG plus corticosteroids in steroid-resistant CIDP in Thailand.A Markov model was constructed to estimate the lifetime costs and outcomes for IVIG plus corticosteroids in comparison with immunosuppressants plus corticosteroids in steroid-resistant CIDP patients from a societal perspective. Efficacy and utility data were obtained from clinical literature, meta-analyses, medical record reviews, and patient interviews. Cost data were obtained from list prices, an electronic hospital database, published source, and patient interviews. All costs [in 2015 US dollars (US$)] and outcomes were discounted at 3 % annually. One-way and probabilistic sensitivity analyses were conducted.In the base-case, the incremental costs and quality-adjusted life years (QALYs) of IVIG plus corticosteroids versus immunosuppressants plus corticosteroids were US$2112.02 and 1.263 QALYs, respectively, resulting in an incremental cost-effectiveness ratio (ICER) of US$1672.71 per QALY gained. Sensitivity analyses revealed that the utility value of disabled patients was the greatest influence on ICER. At a societal willingness-to-pay threshold in Thailand of US$4672 per QALY gained, IVIG plus corticosteroids had a 92.1 % probability of being cost effective.At a threshold of US$4672 per QALY gained, IVIG plus corticosteroids is considered a cost-effective treatment for steroid-resistant CIDP patients in Thailand.

A cross-sectional study was carried out among HCPs in Northwest General Hospital & Research Centre, Hayatabad Peshawar, Pakistan. The purpose of this study was to investigate knowledge, awareness and attitude of HCPs towards influenza vaccination. A total of N=170 questionnaires were distributed among the staff. There was a 97% response rate to this survey (n=165). The median age of the respondents was 30 years and most of them, 98 (59.0%), were from age group of 24-30 years. The majority of the HCPs that participated in this study were male 106 (64.2%), and by profession, the majority were physicians 77 (46.7%), followed by pharmacists and nurses. A majority 114 (69.1%) believed that it was not compulsory for HCPs to get vaccinated for influenza. Top three identified barriers to vaccination were: not everyone is familiar with the availability of the influenza vaccination at their institution (Relative importance weight factors (RIWF)=0.71), due to needle fear I do not like to get vaccinated (RIWF=0.70) and it is not compulsory for healthcare professionals to get vaccinated for influenza (RIWF=0.64). The logistic regression analysis has revealed association for job experience and profession with the most of the eleven knowledge item. However, when overall sum of eleven items were tested to identify the factors affecting the knowledge score, along with profession (-0.215 [-0.389 to 0.040]; p=0.016) and job experience (0.823 [0.521-1.125]; p

Influenza-associated mortality has not been quantified in the Philippines. Here, we constructed multiple negative binomial regression models to estimate the overall and age-specific excess mortality rates (EMRs) associated with influenza in the Philippines from 2006 to 2015. The regression analyses used all-cause mortality as the dependent variable and meteorological controls, time, influenza A and B positivity rates (lagged for up to two time periods), and annual and semiannual cyclical seasonality controls as independent variables. The regression models closely matched observed all-cause mortality. Influenza was estimated to account for a mean of 5,347 excess deaths per year (1.1% of annual all-cause deaths) in the Philippines, most of which (67.1%) occurred in adults aged ≥60 years. Influenza A accounted for 85.7% of all estimated excess influenza deaths. The annual estimated influenza-attributable EMR was 5.09 (95% CI: 2.20-5.09) per 100,000 individuals. The EMR was highest for individuals aged ≥60 years (44.63 [95% CI: 4.51-44.69] per 100,000), second highest for children aged less than 5 years (2.14 [95% CI: 0.44-2.19] per 100,000), and lowest for individuals aged 10 to 19 years (0.48 [95% CI: 0.10-0.50] per 100,000). Estimated numbers of excess influenza-associated deaths were considerably higher than the numbers of influenza deaths registered nationally. Our results suggest that influenza causes considerable mortality in the Philippines-to an extent far greater than observed from national statistics-especially among older adults and young children.

Background Non-small-cell lung cancer (NSCLC) accounts for 85% of all lung cancers and is associated with a poor prognosis. Afatinib is an irreversible ErbB family blocker recommended in clinical guidelines as a first-line treatment for NSCLC which harbours an epidermal growth factor receptor (EGFR) mutation. The objective of this study was to evaluate the cost-effectiveness of afatinib versus pemetrexed-cisplatin for first-line treatment of locally advanced or metastatic EGFR mutation positive NSCLC in Singapore. Methods A partitioned survival model with three health states (progression-free, progressive disease and death) was developed from a healthcare payer perspective. Survival curves from the LUX-Lung 3 trial (afatinib versus pemetrexed-cisplatin chemotherapy) were extrapolated beyond the trial period to estimate the underlying progression-free survival and overall survival parametric distributions. Rates of adverse reactions were also estimated from LUX-Lung 3 while health utilities from overseas were derived from the literature in the absence of local estimates. Direct costs were sourced from public healthcare institutions in Singapore. Incremental cost-effectiveness ratios (ICERs) were calculated over a 5 year time horizon. Deterministic and probabilistic sensitivity analyses and additional scenario analyses were conducted to explore the impact of uncertainties and assumptions on the cost-effectiveness results. Results In the base-case analysis, the ICER for afatinib versus pemetrexed-cisplatin was SG$137,648 per quality-adjusted life year (QALY) gained and SG$109,172 per life-year gained. One-way sensitivity analysis showed the ICER was most sensitive to variations in the utility values, the cost of afatinib and time horizon. Scenario analyses showed that even reducing the cost of afatinib by 50% led to a high ICER which was unlikely to represent a cost-effective use of healthcare resources. Conclusions Compared with pemetrexed-cisplatin, afatinib is not cost-effective as a first-line treatment for advanced EGFR mutation-positive NSCLC in Singapore. The findings from our study will be useful to inform local healthcare decision-making and resource allocations for NSCLC treatments, together with other considerations such as clinical effectiveness, safety and affordability of TKIs.

Simulation models are used widely in pharmacology, epidemiology and health economics (HEs). However, there have been no attempts to incorporate models from these disciplines into a single integrated model. Accordingly, we explored this linkage to evaluate the epidemiological and economic impact of oseltamivir dose optimisation in supporting pandemic influenza planning in the USA. An HE decision analytic model was linked to a pharmacokinetic/pharmacodynamics (PK/PD) – dynamic transmission model simulating the impact of pandemic influenza with low virulence and low transmissibility and, high virulence and high transmissibility. The cost-utility analysis was from the payer and societal perspectives, comparing oseltamivir 75 and 150 mg twice daily (BID) to no treatment over a 1-year time horizon. Model parameters were derived from published studies. Outcomes were measured as cost per quality-adjusted life year (QALY) gained. Sensitivity analyses were performed to examine the integrated model's robustness. Under both pandemic scenarios, compared to no treatment, the use of oseltamivir 75 or 150 mg BID led to a significant reduction of influenza episodes and influenza-related deaths, translating to substantial savings of QALYs. Overall drug costs were offset by the reduction of both direct and indirect costs, making these two interventions cost-saving from both perspectives. The results were sensitive to the proportion of inpatient presentation at the emergency visit and patients’ quality of life. Integrating PK/PD–EPI/HE models is achievable. Whilst further refinement of this novel linkage model to more closely mimic the reality is needed, the current study has generated useful insights to support influenza pandemic planning.

Sacubitril/valsartan reduces cardiovascular death and hospitalizations for heart failure (HF). However, decision-makers need to determine whether its benefits are worth the additional costs, given the low-cost generic status of traditional standard of care.To evaluate the cost-effectiveness of sacubitril/valsartan compared to enalapril in patients with HF and reduced ejection fraction, from the Singapore healthcare payer perspective.A Markov model was developed to project clinical and economic outcomes of sacubitril/valsartan vs enalapril for 66-year-old patients with HF over 10 years. Key health states included New York Heart Association classes I-IV and deaths; patients in each state incurred a monthly risk of hospitalization for HF and cardiovascular death. Sacubitril/valsartan benefits were modeled by applying the hazard ratios (HRs) in PARADIGM-HF trial to baseline probabilities. Primary model outcomes were total and incremental costs and quality-adjusted life years (QALYs) and the incremental cost-effectiveness ratio (ICER) for sacubitril/valsartan relative to enalapril Results: Compared to enalapril, sacubitril/valsartan was associated with an ICER of SGD 74,592 (USD 55,198) per QALY gained. A major driver of cost-effectiveness was the cardiovascular mortality benefit of sacubitril/valsartan. The uncertainty of this treatment benefit in the Asian sub-group was tested in sensitivity analyses using a HR of 1 as an upper limit, where the ICERs ranged from SGD 41,019 (USD 30,354) to SGD 1,447,103 (USD 1,070,856) per QALY gained. Probabilistic sensitivity analyses showed the probability of sacubitril/valsartan being cost-effective was below 1%, 12%, and 71% at SGD 20,000, SGD 50,000, and SGD 100,000 per QALY gained, respectively.At the current daily price sacubitril/valsartan may not represent good value for limited healthcare dollars compared to enalapril in reducing cardiovascular morbidity and mortality in HF in the Singapore healthcare setting. This study highlights the cost-benefit trade-off that healthcare professionals and patients face when considering therapy.

A prospective, observational, longitudinal study was conducted to assess the effectiveness of 75 mg pregabalin (PG) post-hemodialysis (pHD) for treatment-resistant uremic pruritus (UP). A total of forty-five patients completed the entire six week follow-up. At the baseline assessment, the majority of the patients were distressed by the UP frequency and intensity. Sleep (mean = 3.30 ± 1.1), leisure/social activities (mean = 2.90 ± 0.80) and distribution (mean = 2.92 ± 0.34) were the three domains that were primarily effected by the UP. Overall, further reduction in the 5D-itching scale (IS) was noted at day 42, which confirmed a sustained (B = −12.729, CI −13.257 to −12.201, p

Schizophrenia is one of the most expensive psychiatric illnesses. This study compared retrospectively health-care resources consumed 12 months before and 24 months after risperidone long-acting injection (RLAI) treatment in Hong Kong. A mirror-image analysis was conducted using data (N=191) from three public hospitals in Hong Kong from 2003 to 2007. The main outcome measure was hospitalisation cost. Other secondary outcomes such as hospitalisation episodes, outpatient visits and adverse events were also compared. A predictive model was established using linear regression based on generalised estimating equations. Analysis showed that RLAI was associated with a reduction in hospitalisation cost by HK$10,001,390 (24.7%) (HK$40,418,694 vs. HK$30,417,303; P-value

Background/Purpose Pneumococcal diseases caused by Streptococcus pneumoniae can lead to significant morbidity and mortality in young infants and the elderly. The seven-valent pneumococcal conjugate vaccine (PCV7) has been available on the private market in Taiwan since October 2005. To date, there has not been any cost-effectiveness analysis (CEA) of PCV7 in Taiwan. A pharmacoeconomic model populated with local parameters is needed for vaccine decision-making. The aim of the study was to provide a CEA of PCV7 in Taiwan and explore the impact of herd effect and indirect cost on the findings of CEA. Methods A decision analytic model was populated with local epidemiological and economic data to simulate the expected clinical and economic outcomes from a hypothetical vaccinated birth cohort of 191,310 infants compared to no vaccination over a 10-year time horizon. To explore the impact of herd effect, results were presented with and without herd effect. Moreover, the study was conducted from both payer and societal perspectives to examine the impact of indirect cost. One-way sensitivity analyses were performed to evaluate model robustness. The cost-effectiveness of a reduced three-dose schedule was also estimated. Results PCV7 vaccination could prevent 1281 cases of invasive pneumococcal diseases, 178,145 cases of all-cause hospitalized pneumonia, 69,962 cases of all-cause acute otitis media, and 981 deaths over a 10-year time horizon. The vaccination program with an annual cost of NT$1,950.5 million could lead to 15.4% reduction in direct medical costs of NT$6,010 million and 64.1% reduction in indirect costs of NT$9,467 million. The vaccination with a four-dose schedule would lead to an incremental cost of NT$1,183,028 per life-year gained from the payer perspective and NT$619,862 per life-year gained from the societal perspective. Conclusion Taking herd effect and indirect costs into account, PCV7 vaccination is cost-effective in Taiwan. Further pharmacoeconomic model should include herd effect in CEA of infectious disease research.

Cost-effectiveness analysis (CEA) on trial-based data has played an important role in pharmacoeconomics. A regression model can be used to account for patient-level heterogeneity throughout covariates adjustment in CEA. However, the estimates from CEA could be biased if ignoring the censoring issue on effectiveness and costs. This study is to propose a regression model to account for both time-to-event effectiveness and cost.A bivariate regression model was proposed to analyze both effectiveness and cost simultaneously, while censored observations were also taken into account. The regression coefficients were estimated using a Bayesian approach by drawing a random sample from their posterior distribution derived from the Markov chain Monte Carlo (MCMC) method. The proposed method was illustrated using empirical data of anti-platelet therapies to the management of cardiovascular diseases for those patients with high risk of gastrointestinal (GI) bleeding, where cost-effectiveness between different therapies was analyzed under both censored and non-censored circumstances, where the effectiveness was defined as the time to re-hospitalization due to GI complications, and the cost was measured by the total drug expenditure.Under censored circumstances, aspirin plus proton-pump inhibitors (PPIs) was considered more cost-effective than clopidogrel with/without PPIs, as shown in the cost-effectiveness acceptability curve, and clopidogrel was preferred to aspirin for a willingness-to-pay of 89 NTD for delaying 1 day to hospitalization due to GI complications.Ignoring censoring problems could possibly bias the results in CEA. This study has provided an appropriate method to conduct regression-based CEA to improve the estimation which serves its purpose for CEA concerns.The normality assumption for the cost and effectiveness in the bivariate normal regression needs to be examined, and the conclusions may be biased if this assumption is violated. However, when sample size is sufficiently large, a slight deviation from normality would not be a serious problem.

Pneumococcal disease causes large morbidity, mortality and health care utilization and medical and non-medical costs, which can all be reduced by effective infant universal routine immunization programs with pneumococcal conjugate vaccines (PCV). We evaluated the clinical and economic benefits of such programs with either 10- or 13-valent PCVs in Malaysia and Hong Kong by using an age-stratified Markov cohort model with many country-specific inputs. The incremental cost per quality-adjusted life year (QALY) was calculated to compare PCV10 or PCV13 against no vaccination and PCV13 against PCV10 over a 10-year birth cohort's vaccination. Both payer and societal perspectives were used. PCV13 had better public health and economic outcomes than a PCV10 program across all scenarios considered. For example, in the base case scenario in Malaysia, PCV13 would reduce more cases of IPD (+2,296), pneumonia (+705,281), and acute otitis media (+376,967) and save more lives (+6,122) than PCV10. Similarly, in Hong Kong, PCV13 would reduce more cases of IPD cases (+529), pneumonia (+172,185), and acute otitis media (+37,727) and save more lives (+2,688) than PCV10. During the same time horizon, PCV13 would gain over 74,000 and 21,600 additional QALYs than PCV10 in Malaysia and Hong Kong, respectively. PCV13 would be cost saving when compared against similar program with PCV10, under both payer and societal perspective in both countries. PCV13 remained a better choice over PCV10 in multiple sensitivity, scenario, and probabilistic analyses. PCV13s broader serotype coverage in its formulation and herd effect compared against PCV10 were important drivers of differences in outcomes.

Background Seven-valent pneumococcal conjugate vaccines (PCV7) have been used in children for more than a decade. Given the observed increase in disease caused by pneumococcal serotypes not covered by PCV7, an increasing number of countries are switching from 7-valent to 10- and 13-valent PCVs (“PCV10” and “PCV13”). Economic evaluations are important tools to inform decisions and price negotiations to make such a switch. Objective This review aims to provide a critical assessment of economic evaluations involving PCV10 or PCV13, published since 2006. Methods We searched Scopus, ISI Web of Science (SCI and SSCI) and Pubmed to retrieve, select and review relevant studies, which were archived between 1st January 2006 and 31st January 2014. The review protocol involved standard extraction of assumptions, methods, results and sponsorships from the original studies. Results Sixty-three economic evaluations on PCVs published since January 2006 were identified. About half of these evaluated PCV10 and/or PCV13, the subject of this review. At current prices, both PCV13 and PCV10 were likely judged preferable to PCV7. However, the combined uncertainty related to price differences, burden of disease, vaccine effectiveness, herd and serotype replacement effects determine the preference base for either PCV10 or PCV13. The pivotal assumptions and results of these analyses also depended on which manufacturer sponsored the study. Conclusion A more thorough exploration of uncertainty should be made in future analyses on this subject, as we lack understanding to adequately model herd and serotype replacement effects to reliably predict the population impact of PCVs. The introduction of further improved PCVs in an environment of evolving antibiotic resistance and under the continuing influence of previous PCVs implies that the complexity and data requirements for relevant analyses will further increase. Decision makers using these analyses should not just rely on an analysis from a single manufacturer.

Introduction Pharmacogenetic (PGx) test is a useful tool for guiding physician on an initiation of an optimal warfarin dose. To implement of such strategy, the evidence on the economic value is needed. This study aimed to determine the cost-effectiveness of PGx-guided warfarin dosing compared with usual care (UC). Methods A decision analytic model was used to compare projected lifetime costs and quality-adjusted life years (QALYs) accrued to warfarin users through PGx or UC for a hypothetical cohort of 1,000 patients. The model was populated with relevant information from systematic review, and electronic hospital-database. Incremental cost-effectiveness ratios (ICERs) were calculated based on healthcare system and societal perspectives. All costs were presented at year 2013. A series of sensitivity analyses were performed to determine the robustness of the findings. Results From healthcare system perspective, PGx increases QALY by 0.002 and cost by 2,959 THB (99 USD) compared with UC. Thus, the ICER is 1,477,042 THB (49,234 USD) per QALY gained. From societal perspective, PGx results in 0.002 QALY gained, and increases costs by 2,953 THB (98 USD) compared with UC (ICER 1,473,852 THB [49,128 USD] per QALY gained). Results are sensitive to the risk ratio (RR) of major bleeding in VKORC1 variant, the efficacy of PGx-guided dosing, and the cost of PGx test. Conclusion Our finding suggests that PGx-guided warfarin dosing is unlikely to be a cost-effective intervention in Thailand. This evidence assists policy makers and clinicians in efficiently allocating scarce resources.

Invasive pneumococcal disease (IPD) and pneumococcal pneumonia cause substantial morbidity and mortality worldwide. This retrospective study was conducted to estimate the disease burden from pneumococcal disease in older adults in Taiwan from a health insurer's perspective.Data for the years 2002-2009 from patients aged ≥50 years with insurance records indicating pneumococcal meningitis, pneumococcal bacteremia, or hospitalized or outpatient pneumonia were obtained from the National Health Insurance Research Database in Taiwan. Admission data for inpatients, visit data for outpatients, and associated costs were extracted from the database to estimate the incidence, case fatality rates, and direct and indirect costs of pneumococcal disease episodes. These data were applied to the estimated population of Taiwan in 2010 to provide an estimated disease burden for a single year from the payer perspective.The average incidence per 100,000 person years was 2.4 for IPD, 278.8 for hospitalized pneumococcal pneumonia, and 1376.4 for outpatient pneumococcal pneumonia. The average case fatality rate was 12.3% for IPD and 10.0% for hospitalized pneumonia. Hospitalized pneumonia accounted for over 90% of direct medical costs. The incidence of hospitalized pneumococcal pneumonia per 100,000 person years was 84.4 for adults of 50-64 years, 313.1 for adults of 65-74 years, 820.3 for adults of 75-84 years, and 1650.9 for adults of 85+ year of age. In 2010, it was estimated there were over 113,000 episodes of pneumococcal disease, causing almost 2000 deaths, with direct medical costs of more than NT$3.4 billion annually.Pneumococcal disease is a significant cause of mortality and excess healthcare expense among the elderly in Taiwan. Disease burden in older adults increases with advancing age.

Objective To determine the efficacy of a combination of simultaneous shock wave lithotripsy (SWL), hydration with controlled inversion therapy compared with SWL with hydration alone in patients with lower pole calyx stones. Methods Patients with lower pole stones (4-20 mm) were randomized to SWL or SWL with simultaneous inversion therapy (30° head down Trendelenburg position). Standardized shock waves were given to all patients stratified according to stone size. Subsequent standardized shock waves were given to patients with stone fragments determined by plain abdominal radiography and ultrasound by 2 radiologists blinded to treatment at day 1, weeks 2, 4, 12, 24, and at 1 year. The primary endpoint is stone-free rate (SFR) at week 12. Results A total of 140 patients were recruited into the study. Patients were comparable with respect to age, sex, race, and stone parameters at baseline. The overall SFR at week 12 was 72% (n = 49 of 68) in patients with SWL and 76% (n = 54 of 71) in SWL with simultaneous inversion at the end of study (P = .591). There was a trend for SFR to improve over time with >80% of patients being stone-free after 1 year in both groups. No significant adverse effects were noted in both groups of patients. Conclusion Although not statistically significant, SWL with simultaneous inversion is a valuable adjunct in assisting the passage of lower pole renal stones with a SFR of 76%. In clinical practice, this also translates to a 1.28 times improvement in SFR with no or minimal additional costs.

Ordinary least square (OLS) in regression has been widely used to analyze patient-level data in cost-effectiveness analysis (CEA). However, the estimates, inference and decision making in the economic evaluation based on OLS estimation may be biased by the presence of outliers. Instead, robust estimation can remain unaffected and provide result which is resistant to outliers. The objective of this study is to explore the impact of outliers on net-benefit regression (NBR) in CEA using OLS and to propose a potential solution by using robust estimations, i.e. Huber M-estimation, Hampel M-estimation, Tukey's bisquare M-estimation, MM-estimation and least trimming square estimation. Simulations under different outlier-generating scenarios and an empirical example were used to obtain the regression estimates of NBR by OLS and five robust estimations. Empirical size and empirical power of both OLS and robust estimations were then compared in the context of hypothesis testing. Simulations showed that the five robust approaches compared with OLS estimation led to lower empirical sizes and achieved higher empirical powers in testing cost-effectiveness. Using real example of antiplatelet therapy, the estimated incremental net-benefit by OLS estimation was lower than those by robust approaches because of outliers in cost data. Robust estimations demonstrated higher probability of cost-effectiveness compared to OLS estimation. The presence of outliers can bias the results of NBR and its interpretations. It is recommended that the use of robust estimation in NBR can be an appropriate method to avoid such biased decision making.

A high percentage of children with cerebral palsy (CP) have difficulty keeping up with the handwriting demands at school. Previous studies have addressed the effects of proper sitting and writing tool on writing performance, but less on body biomechanics. The aim of this study was to investigate the influence of lower body stabilization and pencil design on body biomechanics in children with CP. Fourteen children (12.31±4.13 years old) with CP were recruited for this study. A crossover repeated measures design was employed, with two independent variables: lower body stabilization (with/without) and pencil (regular/assigned grip height/biaxial). The writing task was to trace the Archimedean spiral mazes. Electromyography (EMG) of the upper extremity, the wrist flexion/extension movements, and the whole body photography were recorded to quantify the changes in posture and upper extremity biomechanics. Two-way repeated measures ANOVA was used for statistical analysis. No significant main effects were revealed in the EMG and wrist kinematics. The lower body stabilization significantly decreased the trunk lateral and forward deviations, and the visual focus-vertical angle. The biaxial pencil and the assigned grip height design significantly decreased the head, shoulder, trunk, and pelvic deviations compared with the regular design. The results indicated that the lower body positioning was effective in improving the trunk posture. A pencil with an assigned grip height or with a biaxial design could improve head, shoulder, trunk and pelvic alignment, but did not influence the muscle exertion of the upper extremity. This study could provide guidelines for parents, teachers and clinicians regarding the selection of writing tools and the knowledge of proper positioning for the children with handwriting difficulties. Further analyses can focus on the design, modification and clinical application of assitive sitting and writing devices for the use in children with handwriting difficulties.

Objectives Streptococcus pneumoniae causes significant morbidity and mortality worldwide. Static pharmacoeconomic models have been used to conduct pharmacoeconomic analyses of pediatric pneumococcal conjugate vaccination programs. The objective of this study was to develop a transmission dynamic model to evaluate the cost-effectiveness of a 13-valent pneumococcal conjugate vaccine (PCV13) in Taiwan. Methods An age-structured transmission dynamic model was populated with parameters from the Taiwanese National Health Insurance Research Database and publicly available sources to evaluate the clinical and economic impact of PCV13. Sensitivity analyses were performed to explore model uncertainties. Results In the base-case analysis, four-dose scheduled universal infant PCV13 vaccination will prevent 5112 cases of invasive pneumococcal diseases, 535,607 cases of all-cause hospitalized pneumonia, 726,986 cases of acute otitis media, and 420 deaths over a 10-year time horizon since 2009. The four-dose vaccination program is estimated to yield an incremental cost-effectiveness ratioof US$38,045 and US$18,299 from payer and societal perspectives. One-way sensitivity analyses indicated that the incremental cost-effectiveness ratio is most sensitive to vaccine price. The 95% confidence interval of the incremental cost-effectiveness ratio was US$10,186 to US$34,563 by multivariate probabilistic sensitivity analyses in the societal perspective. Conclusions With a World Health Organization–recommended cost-effectiveness threshold, the PCV13 vaccination program would be cost-effective in Taiwan. To circumvent the lack of long-term real data, a transmission dynamic model is informative to decision makers on evaluating the long-term cost-effectiveness of PCV13.

Tremendous healthcare resources have been spent on the management of chronic hepatitis B (CHB) and its related complications. Therefore, a proper evaluation of the cost-effectiveness of pharmacotherapy is vital in aid of decision-making. The aim of the present study was to examine the long-term economic and clinical influence if lamivudine was replaced by entecavir in a group of CHB patients.A recently published decision analytic model was adapted to study the cost-effectiveness of 2 years of treatment of entecavir in a hypothetical cohort of 1000 hepatitis B e antigen (HBeAg)-negative CHB patients from a public hospital perspective. Compensated cirrhosis (CC) and de-compensated cirrhosis (DC) and hepatocellular carcinoma (HCC) events were projected to 10 years. Hong Kong-specific health care costs were used. Quality Adjusted Life Years (QALYs) were calculated using the utility values obtained from a local study.In the base case analysis, compared with lamivudine, the use of entecavir was expected to reduce the incidences of CC, DC and HCC by 41.8%, 57.1% and 49.3%, respectively, and lead to a saving of $US 1.17 million in medical cost. The overall disease management cost for entecavir, which was 67.7% higher than lamivudine for 2 years treatment was reduced to 17.2% after projecting 2-year treatment duration to 10 years. The incremental cost per QALY gained for entecavir compared with lamivudine was $US 13 759.Based on the recommended cost-effectiveness threshold of the World Health Organization, entecavir is considered cost-effective compared with lamivudine in treating CHB in Hong Kong when long term medical consequences were considered.

Objectives To develop and validate Osteoporosis Prevention and Awareness Tool (OPAAT) in Malaysia. Methods The OPAAT was modified from the Malaysian Osteoporosis Knowledge Tool and developed from an exploratory study on patients. Face and content validity was established by an expert panel. The OPAAT consists of 30 items, categorized into three domains. A higher score indicates higher knowledge level. English speaking non-osteoporotic postmenopausal women ≥50 years of age and pharmacists were included in the study. Results A total of 203 patients and 31 pharmacists were recruited. Factor analysis extracted three domains. Flesch reading ease was 59.2. The mean±SD accuracy rate was 0.60±0.22 (range: 0.26-0.94). The Cronbach’s α for each domain ranged from 0.286-0.748. All items were highly correlated (Spearman’s rho: 0.761-0.990, p