Catastrophic costs incurred by tuberculosis affected households from Thailand's first national tuberculosis patient cost survey.

Tuberculosis (TB) causes an economic impact on the patients and their households. Although Thailand has expanded the national health benefit package for TB treatment, there was no data on out-of-pocket payments and income losses due to TB from patients and their household perspectives. This national TB patient cost survey was conducted to examine the TB-related economic burden, and assess the proportion of TB patients and their households facing catastrophic total costs because of TB disease. A cross-sectional TB patient cost survey was employed following WHO methods. Structured interviews with a paper-based questionnaire were conducted from October 2019 to July 2021. Both direct and indirect costs incurred from the patient and their household perspective were valued in 2021 and estimated throughout pre- and post-TB diagnosis episodes. We assessed the proportion of TB-affected households facing costs > 20% of household expenditure due to TB. We analyzed 1400 patients including 1382 TB (first-line treatment) and 18 drug-resistant TB patients (DR-TB). The mean total costs per TB episode for all study participants were 903 USD (95% confident interval; CI 771-1034 USD). Of these, total direct non-medical costs were the highest costs (mean, 402 USD, and 95%CI 334-470 USD) incurred per TB-affected household followed by total indirect costs (mean, 393 USD, and 95%CI 315-472 USD) and total direct medical costs (mean, 107 USD, and 95%CI 81-133 USD, respectively. The proportion of TB-affected households facing catastrophic costs was 29.5% (95%CI 25.1-34.0%) for TB (first-line), 61.1% (95%CI 29.6-88.1%) for DR-TB and 29.9% (95%CI 25.6-34.4%) overall. This first national survey highlighted the economic burden on TB-affected households. Travel, food/nutritional supplementation, and indirect costs contribute to a high proportion of catastrophic total costs. These suggest the need to enhance financial and social protection mechanisms to mitigate the financial burden of TB-affected households.

Treatment seeking experiences of ACS patients in Yogyakarta, Indonesia during COVID-19 pandemic: A qualitative study.

Delay in treatment seeking is recognized as a major contributor for Acute Coronary Syndrome (ACS) mortality in Indonesia. Despite the significance of timely treatment, decline in admission and delay in presentation of patients with ACS were consistently reported during the COVID-19 pandemic. These suggested that treatment seeking performance of patients during the pandemic might be different from the previous period. This qualitative study aimed to explore treatment seeking behaviour, barriers in seeking medical treatment, and experiences of patients with ACS in Yogyakarta, Indonesia during COVID-19 pandemic. In depth-interviews were carried out with 30 patients, who were hospitalized with ACS at one of the three selected hospitals in Yogyakarta during the pandemic period. Thematic analysis was performed to create vital explanations for treatment seeking practices of patients with ACS during pandemic. Three significant themes were identified: treatment seeking decisions, barriers in seeking medical treatment during COVID-19, and experiencing both good and bad impression from entering and staying in the hospital. The intensity of ACS symptoms and fear of COVID-19 infection dominated the delay in seeking medical treatment. Strict safety measures, religious belief, and fear of ACS helped patients overcome barriers and seek medical treatment during pandemic. ACS patients also had convenient medical care during the pandemic and believed medical staff would provide excellent care to them. However, visit restriction policy could cause psychological discomfort. Increase awareness of ACS symptoms and the risk of delays ACS treatment are essential to support patients' decisions to seek medical helps in a timely manner at any situations including pandemic. Interventions aim at alleviating psychological distress should also be designed and implemented to improve treatment experiences of ACS patients, who sought medical treatment during the pandemic crisis.

Systematic review of the impact of health care expenditure on health outcome measures: implications for cost-effectiveness thresholds.

OBJECTIVE: Empirical estimates of the impact of healthcare expenditure on health outcome measures may inform the cost-effectiveness threshold (CET) for guiding funding decisions. This study aims to systematically review studies that estimated this, summarize and compare the estimates by country income level. METHODS: We searched PubMed, Scopus, York Research database, and [anonymized] for Reviews and Dissemination database from inception to 1 August 2023. For inclusion, a study had to be an original article, estimating the impact of healthcare expenditure on health outcome measures at a country level, and presented estimates, in terms of cost per quality-adjusted life year (QALY) or disability-adjusted life year (DALY). RESULTS: We included 18 studies with 385 estimates. The median (range) estimates were PPP$ 11,224 (PPP$ 223 - PPP$ 288,816) per QALY gained and PPP$ 5,963 (PPP$ 71 - PPP$ 165,629) per DALY averted. As ratios of Gross Domestic Product per capita (GDPPC), these estimates were 0.376 (0.041-182.840) and 0.318 (0.004-37.315) times of GDPPC, respectively. CONCLUSIONS: The commonly used CET of GDPPC seems to be too high for all countries, but especially low-to-middle-income countries where the potential health losses from misallocation of the same money are greater. REGISTRATION: The review protocol was published and registered in PROSPERO (CRD42020147276).

Economic costs of alcohol consumption in Thailand, 2021.

BACKGROUND: Alcohol is one of the leading risk factors contributing to avoidable economic loss worldwide. Estimates from the economic cost of alcohol consumption studies play an important role in prioritizing healthcare resource use, supporting policy decisions, and justifying budgets for alcohol policy. This study aimed to estimate the economic burden associated with alcohol consumption in Thailand in 2021. METHODS: Prevalence-based cost of illness methodology was employed. The following costs were included in the analysis: healthcare costs; cost of law enforcement; cost of property damage due to road traffic accidents; cost of premature mortality; and cost of absenteeism from out-patient hospital visits and hospitalization. Human capital approach was adopted. All costs were presented in Thai baht, 2021. RESULTS: Alcohol consumption incurred a total estimated economic cost of 165,450.5 million baht, equivalent to 1.02% of Gross Domestic Product (GDP) and 2500 baht per capita. Cost of premature mortality was estimated at 157,918.7 million baht and accounted for the largest proportion of the total cost (95.45%). Healthcare cost was found to be the second highest share representing 4370.1 million baht (2.7% of the total cost). The number of premature death attributable to alcohol consumption in 2021 was estimated at 22,804. CONCLUSIONS: Alcohol continues to impose a substantial economic burden in Thailand. Enforcement of existing well-formulated alcohol control policies is urgently required to mitigate the economic impact of alcohol consumption in the country.

Rituximab for the treatment of relapsing-remitting multiple sclerosis in Thailand: an economic evaluation and budget impact analysis.

BACKGROUND: Multiple sclerosis is an inflammatory demyelination process in the central nervous system (CNS) causing neurological disability and poor quality of life. Currently, Thai Food and Drug Administration (FDA)-approved disease-modifying therapy is costly, and most patients with multiple sclerosis are ineligible for treatment in Thailand as previous studies have challenged its cost-effectiveness. Off-label use of rituximab is inexpensive and highly effective in treating multiple sclerosis, but evidence of its cost-effectiveness in Thailand is yet to be collected. METHODS: This study aimed to evaluate the cost-utility and budget impact of rituximab for multiple sclerosis treatment compared with best supportive care, the standard practice in Thailand to treat the disease. A Markov model with a one-month cycle length and lifetime horizon was applied to compare the costs and outcomes of rituximab and best supportive care based on a societal perspective. Accordingly, incremental cost-effectiveness ratios were estimated. Probabilistic and one-way sensitivity analyses were conducted to investigate parameter uncertainty. In addition, the Markov model was used to assess the 5-year budget impact from the government perspective. RESULTS: A rituximab biosimilar demonstrated higher effectiveness and lower associated costs, compared to best supportive care, with the highest probability of being cost-effective (96%). The probability of relapse was the most sensitive parameter according to the one-way sensitivity analysis. The calculated budget impact of treating patients with multiple sclerosis in Thailand was 26,360,000 Thai baht (THB) or 844,255 United States dollars (USD) in the first fiscal year, and approximately 20,810,000-23,080,000 THB (666,608-739,388 USD) in the next four fiscal years. CONCLUSION: In Thailand, a rituximab biosimilar would reduce the overall costs of multiple sclerosis treatment and should, therefore, be included in the National List of Essential Medicines.

The use of cost-effectiveness analysis for health benefit package design - should countries follow a sectoral, incremental or hybrid approach?

BACKGROUND: Countries around the world are increasingly rethinking the design of their health benefit package to achieve universal health coverage. Countries can periodically revise their packages on the basis of sectoral cost-effectiveness analyses, i.e. by evaluating a broad set of services against a 'doing nothing' scenario using a budget constraint. Alternatively, they can use incremental cost-effectiveness analyses, i.e. to evaluate specific services against current practice using a threshold. In addition, countries may employ hybrid approaches which combines elements of sectoral and incremental cost-effectiveness analysis - a country may e.g. not evaluate the comprehensive set of all services but rather relatively small sets of services targeting a certain condition. However, there is little practical guidance for countries as to which kind of approach they should follow. METHODS: The present study was based on expert consultation. We refined the typology of approaches of cost-effectiveness analysis for benefit package design, identified factors that should be considered in the choice of approach, and developed recommendations. We reached consensus among experts over the course of several review rounds. RESULTS: Sectoral cost-effectiveness analysis is especially suited in contexts with large allocative inefficiencies in current service provision and can, in theory, realize large efficiency gains. However, it may be challenging to implement a comprehensive redesign of the package in practice. Incremental cost-effectiveness analysis is especially relevant in contexts where specific new services may impact the sustainability of the health system. It may potentially support efficiency improvement, but its focus has typically been on new services while existing inefficiencies remain unchallenged. The use of hybrid approach may be a way forward to address the strengths and weaknesses of sectoral and incremental analysis areas. Such analysis may be especially useful to target disease areas with suspected high inefficiencies in service provision, and would then make good use of the available research capacity and be politically rewarding. However, disease-specific analyses bear the risk of not addressing resource allocation inefficiencies across disease areas. CONCLUSIONS: Countries should carefully select their approach of cost-effectiveness analyses for benefit package design, based on their decision-making context.

Efficacy of anti-tuberculosis drugs for the treatment of latent tuberculosis infection: a systematic review and network meta-analysis.

Despite the availability of three network meta-analyses (NMA) examining the efficacy, treatment completion, and adverse events associated with all latent tuberculosis infection (LTBI) treatments, there is currently no evidence to support the notion that the benefits of these treatments outweigh the potential risks. This NMA aimed to conduct a comprehensive comparison and update of the efficacy, treatment completion rates and adverse events associated with recommended treatment options for LTBI for individuals with confirmed LTBI, as outlined in the 2020 World Health Organization (WHO) Consolidated Guidelines for TB preventive treatment. A comprehensive search of the MEDLINE and Scopus databases was conducted until April 2023. The NMA was applied to estimate the risk difference and corresponding 95% confidence interval (CI) using a combination of direct and indirect evidence. The risk-benefit assessment was employed to evaluate the feasibility of the extra benefits in relation to the extra risks. The primary outcomes of interest in this study were active TB disease, completion rates, and adverse events. The meta-analysis incorporated data from 15 studies, which collectively demonstrated that the administration of a placebo resulted in a significant increase in the risk of developing TB disease by 1.279%, compared to the daily intake of isoniazid for 6 months (6H). Furthermore, treatment completion rates were significantly higher when using isoniazid plus rifapentine weekly for 3 months (3HP) and rifampicin daily for 4 months (4R), as compared to 6H. Considering adverse events, the combination of 3HP, 4R, and isoniazid administered daily for 9 months (referred to as 9H) significantly decreased adverse events by 4.53% in comparison to 6H. The risk-benefit assessment showed that alternative treatment regimens (9H, 4R, 3HR and 3HP) had a lower incidence of adverse events, while demonstrating a higher efficacy in preventing TB, as compared to 6H. This review indicates that there were no significant differences observed among various active treatment options in terms of their efficacy in preventing active TB. Moreover, completion rates were higher in 3HP and 4R, and a reduction in adverse events was observed in 3HP, 4R, and 9H.

Efficacy and safety of monoclonal antibody therapy in patients with neuromyelitis optica spectrum disorder: A systematic review and network meta-analysis.

Introduction: Neuromyelitis optica spectrum disorder (NMOSD) is a devastating inflammatory CNS demyelinating disease. Two groups of monoclonal antibodies (mAbs) are used to prevent disease relapse, i.e., Food and Drug Administration (FDA)-approved mAbs (e.g., eculizumab satralizumab, inebilizumab), and off-label mAb drugs (e.g., rituximab and tocilizumab). The FDA-approved mAbs have high efficacy but more expensive compared to the off-labels, and thus are less accessible. This systematic review and network meta-analysis (NMA) was to assess the efficacy and safety of both classes of mAbs compared to the current standard treatments. Methods: Systematically searches were conducted in MEDLINE and SCOPUS from inception until July 2021. Randomized-controlled trials (RCTs) were eligible if they compared any pair of treatments (mAbs, immunosuppressive drugs, or placebo) in adult patients with NMOSD. Studies with AQP4-IgG positive or negative were used in the analysis. Probability of relapse and time to event were extracted from the Kaplan-Meier curves using Digitizer. These data were then converted into individual patient time-to-event data. A one-stage mixed-effect survival model was applied to estimate the median time to relapse and relative treatment effects using hazard ratios (HR). Two-stage NMA was used to determine post-treatment annualized relapse rate (ARR), expanded disability status score (EDSS) change, and serious adverse events (SAE). Risk of bias was assessed using the revised cochrane risk of bias tool. Results: A total of 7 RCTs with 776 patients were eligible in the NMA. Five of the seven studies were rated low risk of bias. Both FDA-approved and off-label mAbs showed significantly lower risk of relapse than standard treatments, with HR (95% CI) of 0.13 (0.07, 0.24) and 0.16 (0.07, 0.37) respectively. In addition, the FDA-approved mAbs had 20% lower risk of relapse than the off-label mAbs, but this did not reach statistical significance. The ARRs were also lower in FDA-approved and off-label mAbs than the standard treatments with the mean-difference of-0.27 (-0.37,-0.16) and-0.31(-0.46,-0.16), respectively. Conclusion: The off-label mAbs may be used as the first-line treatment for improving clinical outcomes including disease relapse, ARR, and SAEs for NMOSD in countries where resources and accessibility of the FDA-approved mAbs are limited. Systematic review registration: https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=283424, identifier: CRD42021283424.

Thai stakeholders' awareness and perceptions of the patient adverse event reporting system for herbal medicines: a qualitative study.

BACKGROUND: In Thailand, the consumption of herbal medicines has been increasing. Adverse events (AEs) of herbal medicines have been identified through the spontaneous reporting system. However, the number of patients reporting AEs of herbal medicines remains limited. AIM: To explore the awareness and perceptions about the patient reporting system and to explore attitudes towards safety of herbal medicines, experiences, and intention to report AEs of herbal medicines. METHOD: Semi-structured in-depth interviews were conducted with stakeholders (patients, community pharmacists, village health volunteers, and consumers who had experienced submitting a complaint about health products to the Consumers Foundation). Additionally, a focus group discussion was held with stakeholders (academics, herbal medicine manufacturers, healthcare professionals, policy maker who was responsible for promoting the use of herbal medicines, pharmacovigilance staff, patient, and representative from patient organisations). The data were audio recorded, transcribed verbatim and analysed using thematic analysis. RESULTS: Fifty participants were interviewed and the focus group discussion included 12 participants. Patients had positive attitudes towards the safety of herbal medicines. Lack of awareness of the patient reporting system was identified. Nevertheless, all stakeholders acknowledged the importance of the safety monitoring of herbal medicines and indicated a willingness to report AEs via the patient reporting system in the future. A simple reporting system, a variety of reporting channels, the provision of feedback, and providing rewards would motivate patients to report AEs. CONCLUSION: Although there is a lack of awareness, this provides a great opportunity to improve patient AE reporting system for herbal medicines in Thailand.

Economic Evaluation of Screening Strategy for Latent Tuberculosis Infection (LTBI) in Contacts of Tuberculosis Patients: Systematic Review and Quality Assessment.

A tuberculin skin test (TST) or interferon-gamma release assay (IGRA) can be used to screen for latent tuberculosis infection (LTBI). Due to its low cost, TST has been used particularly in underdeveloped countries. The limitations of TST were poor specificity in populations with a high prevalence of Bacille Calmette-Guérin (BCG) vaccination and variability of test readers. IGRA is used as an alternative to TST in settings where higher costs can be supported. The lack of studies conducted in high TB incidence countries since previous review, and using relevant assessment tools of the quality appraisal make the need for updated studies and a more comprehensive systematic review. This study aimed to conduct a systematic review of published economic evaluations of screening strategies for LTBI in contacts of TB patients, assess the quality of these studies, and compare the assessment results related to a country's income level in order to provide information to other countries. The databases were searched in January 2022 including MEDLINE and Scopus. Two independent reviewers evaluated the included studies based on eligibility criteria, data extraction, and quality assessment. Eleven economic evaluations of LTBI diagnostic tests in TB contacts were included. Most studies were conducted in high-income countries (91%) and used cost-effectiveness analysis methods (73%). The quality assessment of reporting and data sources was appropriate, ranging from 71% to 89%. Interventions varied from study to study. The outcomes were cost per life years gained (27%), cost per quality-adjusted life year gained (27%), cost per TB case prevented (36%), and cost per close contact case (10%). In high-income countries which were not countries with high TB burden, the use of IGRA alone for screening TB contacts was cost-effective, whereas TST was cost-effective in only two studies. In comparison to TST, IGRA could reduce false-positive results, resulting in fewer patients undergoing TB treatment and preventive treatment.

Potential changes in vaccine access and policy landscape in Thailand post COVID-19 pandemic.

The COVID-19 pandemic has had a dramatic impact on society, but little is known about how the pandemic affects the vaccine policy landscape and public perception of vaccines in Thailand. This study aims to describe potential changes in Thailand's policy landscape post-pandemic. We performed a literature review and in-depth interviews with 12 key informants to understand the policy landscape in Thailand. The findings were shared in a policy forum in December 2021. Several key findings were summarized. Funding and development have been thriving during the pandemic. However, a long-term commitment from all stakeholders is required to maintain policy continuation. A public-private partnership should be considered. The regulatory body needs to be prepared for product authorization. The vaccine introduction decision-making process, and investment in prevention and promotion, should further be discussed. In summary, it is important to reshape the environment and mentality of all stakeholders to create a sustainable and self-sufficient vaccine ecosystem.

Cost-Utility Analysis of Community Case Management for Malaria Control in Burundi.

BACKGROUND: The community case management (CCM) program for malaria control is a community-based strategy implemented to regulate malaria in children in Burundi. This study compared the cost and utility of implementing the CCM program combined with health facility management (HFM) versus HFM alone for malaria control in children under five in Burundi. METHODS: This study constructed a five-year Markov model with one-week cycles to estimate cost-utility and budget impact analysis (BIA). The model defined 10 health states, simulating the progression of the disease and the risk of recurrent malaria in children under five years of age. Cost data were empirically collected and presented for 2019. Incremental cost per disability-adjusted life year (DALY) averted, and a five-year budget was estimated. One-way and probabilistic sensitivity analyses (PSAs) were then performed. RESULTS: From provider and societal perspectives, combining the CCM program with HFM for malaria control in Burundi was more cost-effective than implementing HFM alone. The addition of CCM, using artesunate amodiaquine (ASAQ) as the first-line treatment, increased by US$1.70, and US$ 1.67 per DALY averted from the provider and societal perspectives, respectively. Using Artemether Lumefantrine (AL) as the first-line treatment, adding the CCM program to HFM increased by US$ 1.92, and US$ 1.87 per DALY averted from the provider and societal perspectives. At a willingness-to-pay of one GDP/capita, the CCM program remained a 100% chance of being cost-effective. In addition, implementing the program for five years requires a budget of US$ 15 800 486-19 765 117. CONCLUSION: Implementing the CCM program and HFM is value for money for malaria control in Burundi. The findings can support decision-makers in Burundi in deciding on resource allocation, especially during the program's scale up.

Does the Choice of Health Metric, DALY or QALY, Influence Conclusions of Health Economic Evaluation? A Case Study of Rotavirus Vaccine in Burundi.

BACKGROUND: Two metrics, quality-adjusted life-year (QALY) and disability-adjusted life-year (DALY), have been commonly used to measure health benefits associated with health interventions. This study aimed to explore the effect of the choice of health metric (DALY or QALY) on economic evaluation conclusion. METHODS: A previous published model for a cost-utility analysis (CUA) of rotavirus vaccine was adapted to estimate the QALYs gained and DALYs averted from four rotavirus vaccines: Rotarix, RotaTeq, Rotavac, and Rotasiil. The study was conducted in both Burundi provider and societal perspectives over a five-year time horizon. Disability weights (DW) were derived from the Global Burden of Disease (GBD) study. Scenario analysis was performed to evaluate the impact of age weights and source of utility weight. RESULTS: In base-case analysis, the QALYs gained ranged from 46 to 78% of the DALYs averted. The incremental cost-effectiveness ratios (ICER) per QALY gained were higher than ICER per DALY averted by 28 to 113%, leading to less favorable cost effectiveness. The QALYs gained from using 1-DW as utility weight were slightly higher than those using EQ-5D utility weight obtained from previous literature, yet less likely to alter CUA conclusions. When age-weighting was incorporated in the DALY calculation, the ICERs per DALY averted were reduced leading to more favorable cost effectiveness. CONCLUSION: In case of rotavirus diarrhea, in which mortality burden is considered larger than morbidity due to short duration of disease, although the use of DALY consistently led to more favorable cost-effective result than the use of QALY such effects were considered small and less likely to affect the EE conclusion under current CET of 1 GDP per capita.

Comparison of Patient Adverse Drug Reaction Reporting Systems in Nine Selected Countries.

Patients are recognized as important players in the pharmacovigilance system. This study aims to describe and compare the characteristics of patient reporting systems, reporting forms, awareness raising-activities, and the statistics related to patient reporting in the selected countries. Fifteen countries (eight Western countries and seven Asian countries) were purposively selected. A questionnaire survey was distributed to national pharmacovigilance authorities in those countries. Nine countries (five Western countries and four Asian countries) returned the questionnaire. A review of the websites of national pharmacovigilance centres was conducted. The proportion of patient reports in the selected Western countries ranged from 57.83% to 14.37%, while it was accounted for less than 1% in the selected Asian countries. Currently, patients in all nine countries can report adverse drug reactions online via a website. The number of clicks from the national pharmacovigilance website to reach the online reporting form range from one to five clicks. Countries with higher patient reporting rates seemed to share the following characteristics; provision of feedback, engagement with patient organizations, and implementation of several activities to raise the awareness of the general public on the importance of pharmacovigilance. To increase the number of patient reports, the strengths of each country's system should be adopted.

Priority setting of vaccine introduction in Bangladesh: a multicriteria decision analysis study.

OBJECTIVE: To prioritise vaccines for introduction in Bangladesh. METHODS: Multicriteria decision analysis (MCDA) process was used to prioritise potential vaccines for introduction in Bangladesh. A set of criteria were identified, weighted and assigned scores by relevant stakeholders (n=14) during workshop A. The performance matrix of the data of vaccines against the criteria set was constructed and validated with the experts (n=6) in workshop B. The vaccines were ranked and appraised by another group of stakeholders (n=10) in workshop C, and the final workshop D involved the dissemination of the findings to decision-makers (n=28). RESULTS: Five criteria including incidence rate, case fatality rate, vaccine efficacy, size of the population at risk and type of population at risk were used quantitatively to evaluate and to score the vaccines. Two other criteria, cost-effectiveness and outbreak potentiality, were considered qualitatively. On deliberation, the Japanese encephalitis (JE) vaccine was ranked top to be recommended for introduction in Bangladesh. CONCLUSIONS: Based on the MCDA results, JE vaccine is planned to be recommended to the decision-makers for introduction into the national vaccine benefit package. The policymakers support the use of systematic evidence-based decision-making processes such as MCDA for vaccine introduction in Bangladesh, and to prioritise health interventions in the country.

Neoadjuvant Treatment with HER2-Targeted Therapies in HER2-Positive Breast Cancer: A Systematic Review and Network Meta-Analysis.

This systematic review aimed to identify neoadjuvant anti-human epidermal growth factor receptor 2 (HER2) therapies with the best balance between efficacy and safety. METHODS: A network meta-analysis was applied to estimate the risk ratios along with 95% confidence intervals (CIs) for pathological complete response (pCR) and serious adverse events (SAE). A mixed-effect parametric survival analysis was conducted to assess the disease-free survival (DFS) between treatments. RESULTS: Twenty-one RCTs with eleven regimens of neoadjuvant anti-HER2 therapy (i.e., trastuzumab + chemotherapy (TC), lapatinib + chemotherapy (LC), pertuzumab + chemotherapy (PC), pertuzumab + trastuzumab (PT), trastuzumab emtansine + pertuzumab (T-DM1P), pertuzumab + trastuzumab + chemotherapy (PTC), lapatinib + trastuzumab + chemotherapy (LTC), trastuzumab emtansine + lapatinib + chemotherapy (T-DM1LC), trastuzumab emtansine + pertuzumab + chemotherapy(T-DM1PC), PTC followed by T-DM1P (PTC_T-DM1P), and trastuzumab emtansine (T-DM1)) and chemotherapy alone were included. When compared to TC, only PTC had a significantly higher DFS with a hazard ratio (95% CI) of 0.54 (0.32-0.91). The surface under the cumulative ranking curve (SUCRA) suggested that T-DM1LC (91.9%) was ranked first in achieving pCR, followed by the PTC_T-DM1P (90.5%), PTC (74.8%), and T-DM1PC (73.5%) regimens. For SAEs, LTC, LC, and T-DM1LC presented with the highest risks (SUCRA = 10.7%, 16.8%, and 20.8%), while PT (99.2%), T-DM1P (88%), and T-DM1 (83.9%) were the safest regimens. The T-DM1PC (73.5% vs. 71.6%), T-DM1 (70.5% vs. 83.9%), and PTC_T-DM1P (90.5% vs. 47.3%) regimens offered the optimal balance between pCR and SAE. CONCLUSIONS: The T-DM1PC, T-DM1, and PTC_T-DM1P regimens had the optimal balance between efficacy and safety, while DFS was highest for the PTC regimen. However, these results were based on a small number of studies, and additional RCTs assessing the efficacy of regimens with T-DM1 are still needed to confirm these findings.

How Economic Analysis Increases the Awareness of Clinical Services: A Case of Diabetes Mellitus at a Teaching Hospital in Myanmar.

OBJECTIVES: Myanmar faces a growing epidemic of type 2 diabetes mellitus, which has significant impact on the individual health and health service system; nevertheless, reliable cost estimate for treating diabetes is still unknown. Therefore, this study aimed to explore the treatment cost of hospitalization by type 2 diabetes mellitus and the association of complications and comorbidities with the treatment cost. METHODS: The retrospective incidence-based cost of illness analysis was performed at the diabetes ward of 800-bed teaching hospital in Yangon, Myanmar. The data were retrieved from hospital financial reports and patient's medical records for the fiscal year 2017 to 2018. Data was analyzed by using descriptive statistics and multivariate statistics. One-way sensitivity analysis was used to assess the uncertainty of input parameters. RESULTS: This study involved 87 inpatients with type 2 diabetes mellitus with an average length of stay of 16.1 ± 12.6 days. Of the study sample, 67% had complications whereas 74% had comorbidities. The average treatment cost per admission was $718.7 (equal to 58% of gross domestic product - GDP per capita) at 2018 prices. Based on the multiple regression analysis, cost savings per admission were $276.5, $307.3, and $319.5 from preventing foot ulcer, nephropathy, and retinopathy, respectively. CONCLUSIONS: This study found that the treatment of diabetes is costly because of its preventable health consequences. Better disease management to prevent complications results in considerable cost savings. This quantitative evidence would increase awareness in health service system.

Economic evaluation of direct oral anticoagulants (DOACs) versus vitamin K antagonists (VKAs) for stroke prevention in patients with atrial fibrillation: a systematic review and meta-analysis.

OBJECTIVES: To assess cost-effectiveness of direct oral anticoagulants (DOACs) compared with vitamin K antagonists (VKAs) for stroke prevention in atrial fibrillation (AF) by pooling incremental net benefits (INBs). DESIGN: Systematic review and meta-analysis. SETTING: We searched PubMed, Scopus and Centre for Evaluation of Value and Risks in Health Registry from inception to December 2019. PARTICIPANTS: Patients with AF. MAIN OUTCOME MEASURES: The INB was defined as a difference of incremental effectiveness multiplied by willing to pay threshold minus the incremental cost; a positive INB indicated favour treatment. These INBs were pooled (stratified by level of country income, perspective, time-horizon, model types) with a random-effects model if heterogeneity existed, otherwise a fixed effects model was applied. Heterogeneity was assessed using Q test and I2 statistic. Risk of bias was assessed using the economic evaluations bias (ECOBIAS) checklist. RESULTS: A total of 100 eligible economic evaluation studies (224 comparisons) were included. For high-income countries (HICs) from a third-party payer (TPP) perspective, the pooled INBs for DOAC versus VKA pairs were significantly cost-effective with INBs (95% CI) of $6632 ($2961.67 to $10 303.72; I2=59.9%), $6353.24 ($4076.03 to $8630.45; I2=0%), $7664.58 ($2979.79 to $12 349.37; I2=0%) and $8573.07 ($1877.05 to $15 269.09; I2=0%) for dabigatran, apixaban, rivaroxaban and edoxaban relative to VKA, respectively but only dabigatran was significantly cost-effective from societal perspective (SP) with an INB of $11 746.96 ($2429.34 to $21 064.59; I2=52.4%). The pooled INBs of all comparisons for upper-middle income countries (UMICs) were not significantly cost-effective. The ECOBIAS checklist indicated that risk of bias was mostly low for most items with the exception of five items which should be less influenced on pooling INBs. CONCLUSIONS: Our meta-analysis provides comprehensive economic evidence that allows policy makers to generalise cost-effectiveness data to their local context. All DOACs may be cost-effective compared with VKA in HICs with TPP perspective. The pooling results produced moderate to high heterogeneity particularly in UMICs. Further studies are required to inform UMICs with SP. PROSPERO REGISTERATION NUMBER: CRD 42019146610.

Cost-Utility Analysis of Dapagliflozin Compared to Sulfonylureas for Type 2 Diabetes as Second-Line Treatment in Indian Healthcare Payer's Perspective.

BACKGROUND: Type 2 diabetes mellitus (T2DM) is a leading health issue, causing economic burden in India. Pharmacotherapy is a major cost driver in diabetic care usually funded through out of pocket expenditure; however, there has been a very limited economic evaluation evidence to guide the choice of diabetes pharmacotherapy in India. Therefore, this study aims to evaluate the long-term cost-effectiveness of dapagliflozin (sodium glucose transporter 2 inhibitor) compared to commonly used sulfonylureas as second-line drugs in Indian patients with T2DM. METHODS: Cost-utility analysis was employed to estimate the costs and health outcomes using a Markov model with 1-year cycle length during a lifetime horizon based on an Indian payer's perspective. A treatment pathway with dapagliflozin as second-line therapy was compared to sulfonylureas after failure of initial metformin therapy. Clinical and cost data were collected from literature reviews and available secondary data sources. Both costs and outcomes were discounted at a 3% annual discount rate. The results were presented as the incremental cost-effectiveness ratio (ICER). One-way and probabilistic sensitivity analyses were performed to test parameter uncertainties. RESULTS: Compared to sulfonylurea, dapagliflozin was estimated to incur an additional cost of ₹182,632 (US$2,446) with an expected 3.49 life years (LY) or 1.72 quality adjusted life years (QALY) gained, resulting in an ICER of ₹52,270 (US$699) per LY gained, or ₹106,133 (US$1,421) per QALY gained. Uncertainty analyses showed that the ICER values were not sensitive to changes in most parameters. CONCLUSION: Dapagliflozin would be cost-effective compared to sulfonylureas as the second line added to metformin for T2DM patients based on an Indian payer's perspective.

A Systematic Review of Demand-Side Methods of Estimating the Societal Monetary Value of Health Gain.

OBJECTIVES: Although many reviews of the literature on cost-effectiveness thresholds (CETs) exist, the availability of new studies and the absence of a fully comprehensive analysis warrant a new review. This study systematically reviews demand-side methods for estimating the societal monetary value of health gain. METHODS: Several electronic databases were searched from inception to October 2019. To be included, a study had to be an original article in any language, with a clearly described method for estimating the societal monetary values of health gain and with all estimated values reported. Estimates were converted to US dollars ($), using purchasing power parity (PPP) exchange rates and the gross domestic product (GDP) per capita (2019). RESULTS: We included 53 studies; 45 used direct approach and 8 used indirect approach. Median estimates from the direct approach were PPP$ 24 942 (range 554-1 301 912) per quality-adjusted life-year (QALY), which were typically 0.53 (range 0.02-24.08) GDP per capita. Median estimates using the indirect approach were PPP$ 310 051 (range 36 402-7 574 870) per QALY, which accounted for 7.87 (range 0.68-116.95) GDP per capita. CONCLUSIONS: Our review found that the societal values of health gain or CETs were less than GDP per capita. The great variety in methods and estimates suggests that a more standardized and internationally agreed methodology for estimating CET is warranted. Multiple CETs may have a role when QALYs are not equally valued from a societal perspective (eg, QALYs accruing to people near death compared with equivalent QALYs to others).