Cost-utility analysis of atezolizumab combined with bevacizumab for unresectable hepatocellular carcinoma in Thailand.

BACKGROUND: Clinical trials have proven the efficacy and safety of atezolizumab combined with bevacizumab (A+B) in treating unresectable hepatocellular carcinoma (uHCC). This study aimed to assess the cost-utility of A+B compared to best supportive care (BSC) among uHCC patients in Thailand. METHODS: We conducted a cost-utility analysis from a societal perspective. We used a three-state Markov model to estimate relevant costs and health outcomes over the lifetime horizon. Local cost and utility data from Thai patients were applied. All costs were adjusted to 2023 values using the consumer price index. We reported results as incremental cost-effectiveness ratios (ICERs) in United States dollars ($) per quality-adjusted life year (QALY) gained. We discounted future costs and outcomes at 3% per annum. We then performed one-way sensitivity analysis and probabilistic sensitivity analysis to assess parameter uncertainty. The budget impact was conducted to estimate the financial burden from the governmental perspective over a five-year period. RESULTS: Compared to BSC, A+B provided a better health benefit with 0.8309 QALY gained at an incremental lifetime cost of $45,357. The ICER was $54,589 per QALY gained. The result was sensitive to the hazard ratios for the overall survival and progression-free survival of A+B. At the current Thai willingness-to-pay (WTP) threshold of $4,678 per QALY gained, the ICER of A+B remained above the threshold. The projected budgetary requirements for implementing A+B in the respective first and fifth years would range from 8.2 to 27.9 million USD. CONCLUSION: Although A+B yielded the highest clinical benefit compared with BSC for the treatment of uHCC patients, A+B is not cost-effective in Thailand at the current price and poses budgetary challenges.

Cost-utility analysis of the screening program for early oral cancer detection in Thailand.

OBJECTIVE: To assess the cost-utility of an oral precancer screening program compared to a no-screening program in Thailand. MATERIALS AND METHODS: Markov models were performed to simulate costs and Quality Adjusted Life-Years (QALYs) of both the screening and no-screening programs in the Thai population aged over 40 years. There are four steps to the screening program in Thailand: 1) mouth self-examination (MSE); 2) visual examination by trained dental nurses (VETDN); 3) visual examination by trained dentists (VETD); and 4) visual examination by oral surgeons (VEOS). The societal perspective and lifetime horizon were applied. Variables used were derived from the pilot study of the oral precancer screening program in Roi Et province as well as through patient interviews and local and international literature reviews. Results were presented in terms of Incremental Cost-Effectiveness Ratios (ICER). Sensitivity analysis was performed to assess parameters uncertainty. RESULTS: The screening program yielded higher costs (1,362 Baht) and QALYs (0.0044 years) than the no screening program, producing an ICER of 311,030 Baht per QALY gained. This indicates that the screening program is cost-ineffective in the Thai context, where the cost-effectiveness threshold is THB 160,000 per QALY gained. However, the programs will be cost-effective if the screening program are improved in one of three ways; 1) the sensitivity and specificity of MSE are more than 60%, 2) the sensitivity and specificity of VETDN are greater than 90%, or 3) the low accuracy steps like MSE or VETDN are removed from the screening program. CONCLUSION: The screening program is found to be cost-ineffective for oral precancer detection in Thailand. However, this study suggests 3 alternative policy options to ensure the cost-effectiveness of the program.

An economic analysis of chromosome testing in couples with children who have structural chromosome abnormalities.

BACKGROUND: Structural chromosome abnormalities can cause significant negative reproductive outcomes as they typically result in morbidity and mortality of newborns. The prevalence of structural chromosomal abnormalities in live births is at least 0.05%, of which many of them have parental origins. It is uncommon to predict structural chromosome abnormalities at birth in the first child but it is possible to prevent repeated abnormalities through screening and diagnostic programmes. This study will provide an economic analysis of the prenatal detection of these abnormalities. METHODS: A cost-benefit analysis using a decision analytic model was employed to compare the status quo (doing nothing) with two interventional strategies. The first strategy (Strategy I) is preconceptional screening plus amniocentesis, and the second strategy (Strategy II) is amniocentesis alone. The monetary values in Thai baht (THB) were adjusted to international dollars (I$) using purchasing power parity (PPP) (I$1 = THB 17.60 for the year 2013). The robustness of the results was tested by applying a probabilistic sensitivity analysis. RESULTS: Both diagnostic strategies can reduce approximately 10.7-11.1 births with abnormal chromosomes per 1,000 diagnosed couples. The benefit cost ratios were 1.62 for Strategy I and 1.24 for Strategy II. Net present values per 1,000 diagnoses in couples were I$464,000 for Strategy I and I$267,000 for Strategy II. The probabilistic sensitivity analysis suggested that the cost-benefit analysis was sufficiently robust, confirming that both strategies provided higher benefits than costs. CONCLUSIONS: Since the benefits of both diagnostic strategies exceeded their costs, both strategies are economical-with Strategy I being more economically attractive. Strategy I is superior to Strategy II because it decreases the risk of normal children potentially dying from the amniocentesis process.

Towards the introduction of pneumococcal conjugate vaccines in Bhutan: A cost-utility analysis to determine the optimal policy option.

BACKGROUND: Due to competing health priorities and limited resources, many low-income countries, even those with a high disease burden, are not able to introduce pneumococcal conjugate vaccines. OBJECTIVE: To determine the cost-utility of 10- and 13-valent pneumococcal conjugate vaccines (PCV10 and PCV13) compared to no vaccination in Bhutan. METHODS: A model-based cost-utility analysis was performed in the Bhutanese context using a government perspective. A Markov simulation model with one-year cycle length was used to estimate the costs and outcomes of three options: PCV10, PCV13 and no PCV programmes for a lifetime horizon. A discount rate of 3% per annum was applied. Results are presented using an incremental cost-effectiveness ratio (ICER) in United State Dollar per quality-adjusted life year (QALY) gained (USD 1 = Ngultrum 65). A one-way sensitivity analysis and a probabilistic sensitivity analysis were conducted to assess uncertainty. RESULTS: Compared to no vaccination, PCV10 and PCV13 gained 0.0006 and 0.0007 QALYs with additional lifetime costs of USD 0.02 and USD 0.03 per person, respectively. PCV10 and PCV13 generated ICERs of USD 36 and USD 40 per QALY gained compared to no vaccination. In addition, PCV13 produced an ICER of USD 92 compared with PCV10. When including PCV into the Expanded Programme on Immunization, the total 5-year budgetary requirement is anticipated to increase to USD. 3.77 million for PCV10 and USD 3.75 million for PCV13. Moreover, the full-time equivalent (FTE) of one health assistant would increase by 2.0 per year while the FTE of other health workers can be reduced each year, particularly of specialist (0.6-1.1 FTE) and nurse (1-1.6 FTE). CONCLUSION: At the suggested threshold of 1xGDP per capita equivalent to USD 2708, both PCVs are cost-effective in Bhutan and we recommend that they be included in the routine immunization programme.

Incorporating economies of scale in the cost estimation in economic evaluation of PCV and HPV vaccination programmes in the Philippines: a game changer?

BACKGROUND: Many economic evaluations ignore economies of scale in their cost estimation, which means that cost parameters are assumed to have a linear relationship with the level of production. Economies of scale is the situation when the average total cost of producing a product decreases with increasing volume caused by reducing the variable costs due to more efficient operation. This study investigates the significance of applying the economies of scale concept: the saving in costs gained by an increased level of production in economic evaluation of pneumococcal conjugate vaccines (PCV) and human papillomavirus (HPV) vaccinations. METHODS: The fixed and variable costs of providing partial (20% coverage) and universal (100% coverage) vaccination programs in the Philippines were estimated using various methods, including costs of conducting questionnaire survey, focus-group discussion, and analysis of secondary data. Costing parameters were utilised as inputs for the two economic evaluation models for PCV and HPV. Incremental cost-effectiveness ratios (ICERs) and 5-year budget impacts with and without applying economies of scale to the costing parameters for partial and universal coverage were compared in order to determine the effect of these different costing approaches. RESULTS: The program costs of the partial coverage for the two immunisation programs were not very different when applying and not applying the economies of scale concept. Nevertheless, the program costs for universal coverage were 0.26 and 0.32 times lower when applying economies of scale compared to not applying economies of scale for the pneumococcal and human papillomavirus vaccinations, respectively. ICERs varied by up to 98% for pneumococcal vaccinations, whereas the change in ICERs in the human papillomavirus vaccination depended on both the costs of cervical cancer screening and the vaccination program. This results in a significant difference in the 5-year budget impact, accounting for 30 and 40% of reduction in the 5-year budget impact for the pneumococcal and human papillomavirus vaccination programs. CONCLUSIONS: This study demonstrated the feasibility and importance of applying economies of scale in the cost estimation in economic evaluation, which would lead to different conclusions in terms of value for money regarding the interventions, particularly with population-wide interventions such as vaccination programs. The economies of scale approach to costing is recommended for the creation of methodological guidelines for conducting economic evaluations.

Vaccination program in a resource-limited setting: A case study in the Philippines.

OBJECTIVE: Implementing national-level vaccination programs involves long-term investment, which can be a significant financial burden, particularly in resource-limited settings. Although many studies have assessed the economic impacts of providing vaccinations, evidence on the positive and negative implications of human resources for health (HRH) is still lacking. Therefore, this study aims to estimate the HRH impact of introducing pneumococcal conjugate vaccine (PCV) using a model-based economic evaluation. METHODS: This study adapted a Markov model from a prior study that was conducted in the Philippines for assessing the cost-effectiveness of 10-valent and 13-valent PCV compared to no vaccination. The Markov model was used for estimating the number of cases of pneumococcal-related diseases, categorized by policy options. HRH-related parameters were obtained from document reviews and interviews using the quantity, task, and productivity model (QTP model). RESULTS: The number of full-time equivalent (FTE) of general practitioners, nurses, and midwives increases significantly if the universal vaccine coverage policy is implemented. A universal coverage of PCV13 - which is considered to be the best value for money compared to other vaccination strategies - requires an additional 380 FTEs for general practitioners, 602 FTEs for nurses, and 205 FTEs for midwives; it can reduce the number of FTEs for medical social workers, paediatricians, infectious disease specialists, neurologists, anaesthesiologists, radiologists, ultrasonologists, medical technologists, radiologic technologists, and pharmacists by 7, 17.9, 9.7, 0.4, 0.1, 0.7, 0.1, 12.3, 2, and 9.7, respectively, when compared to the no vaccination policy. CONCLUSION: This is the first attempt to estimate the impact of HRH alongside a model-based economic evaluation study, which can be eventually applied to other vaccine studies, especially those which inform resource allocation in developing settings where not only financial resources but also HRH are constrained.

Do Pneumococcal Conjugate Vaccines Represent Good Value for Money in a Lower-Middle Income Country? A Cost-Utility Analysis in the Philippines.

OBJECTIVES: The objective of this study is to assess the value for money of introducing pneumococcal conjugate vaccines as part of the immunization program in a lower-middle income country, the Philippines, which is not eligible for GAVI support and lower vaccine prices. It also includes the newest clinical evidence evaluating the efficacy of PCV10, which is lacking in other previous studies. METHODS: A cost-utility analysis was conducted. A Markov simulation model was constructed to examine the costs and consequences of PCV10 and PCV13 against the current scenario of no PCV vaccination for a lifetime horizon. A health system perspective was employed to explore different funding schemes, which include universal or partial vaccination coverage subsidized by the government. Results were presented as incremental cost-effectiveness ratios (ICERs) in Philippine peso (Php) per QALY gained (1 USD = 44.20 Php). Probabilistic sensitivity analysis was performed to determine the impact of parameter uncertainty. RESULTS: With universal vaccination at a cost per dose of Php 624 for PCV10 and Php 700 for PCV13, both PCVs are cost-effective compared to no vaccination given the ceiling threshold of Php 120,000 per QALY gained, yielding ICERs of Php 68,182 and Php 54,510 for PCV10 and PCV13, respectively. Partial vaccination of 25% of the birth cohort resulted in significantly higher ICER values (Php 112,640 for PCV10 and Php 84,654 for PCV13) due to loss of herd protection. The budget impact analysis reveals that universal vaccination would cost Php 3.87 billion to 4.34 billion per annual, or 1.6 to 1.8 times the budget of the current national vaccination program. CONCLUSION: The inclusion of PCV in the national immunization program is recommended. PCV13 achieved better value for money compared to PCV10. However, the affordability and sustainability of PCV implementation over the long-term should be considered by decision makers.

Seasonal influenza vaccination for children in Thailand: a cost-effectiveness analysis.

BACKGROUND: Seasonal influenza is a major cause of mortality worldwide. Routine immunization of children has the potential to reduce this mortality through both direct and indirect protection, but has not been adopted by any low- or middle-income countries. We developed a framework to evaluate the cost-effectiveness of influenza vaccination policies in developing countries and used it to consider annual vaccination of school- and preschool-aged children with either trivalent inactivated influenza vaccine (TIV) or trivalent live-attenuated influenza vaccine (LAIV) in Thailand. We also compared these approaches with a policy of expanding TIV coverage in the elderly. METHODS AND FINDINGS: We developed an age-structured model to evaluate the cost-effectiveness of eight vaccination policies parameterized using country-level data from Thailand. For policies using LAIV, we considered five different age groups of children to vaccinate. We adopted a Bayesian evidence-synthesis framework, expressing uncertainty in parameters through probability distributions derived by fitting the model to prospectively collected laboratory-confirmed influenza data from 2005-2009, by meta-analysis of clinical trial data, and by using prior probability distributions derived from literature review and elicitation of expert opinion. We performed sensitivity analyses using alternative assumptions about prior immunity, contact patterns between age groups, the proportion of infections that are symptomatic, cost per unit vaccine, and vaccine effectiveness. Vaccination of children with LAIV was found to be highly cost-effective, with incremental cost-effectiveness ratios between about 2,000 and 5,000 international dollars per disability-adjusted life year averted, and was consistently preferred to TIV-based policies. These findings were robust to extensive sensitivity analyses. The optimal age group to vaccinate with LAIV, however, was sensitive both to the willingness to pay for health benefits and to assumptions about contact patterns between age groups. CONCLUSIONS: Vaccinating school-aged children with LAIV is likely to be cost-effective in Thailand in the short term, though the long-term consequences of such a policy cannot be reliably predicted given current knowledge of influenza epidemiology and immunology. Our work provides a coherent framework that can be used for similar analyses in other low- and middle-income countries.

Economic evaluation of 3-drug antiretroviral regimens for the prevention of mother-to-child HIV transmission in Thailand.

The current program for prevention of mother-to-child HIV transmission in Thailand recommends a 2-drugs regimen for HIV-infected pregnant women with a CD4 count >200 cells/mm(3). This study assesses the value for money of 3 antiretroviral drugs compared with zidovudine (AZT)+single-dose nevirapine (sd-NVP). A decision tree was constructed to predict costs and outcomes using the governmental perspective for assessing cost-effectiveness of 3-drug regimens: (1) AZT, lamivudine, and efavirenz and (2) AZT, 3TC, and lopinavir/ritonavir, in comparison with the current protocol, AZT+sd-NVP. The 3-drug antiretroviral regimens yield lower costs and better health outcomes compared with AZT+sd-NVP. Although these 3-drug regimens offer higher program costs and health care costs for premature birth, they save money significantly in regard to pediatric HIV treatment and treatment costs for drug resistance in mothers. The 3-drug regimens are cost-saving interventions. The findings from this study were used to support a policy change in the national recommendation.

Cost-utility analysis of dasatinib and nilotinib in patients with chronic myeloid leukemia refractory to first-line treatment with imatinib in Thailand.

BACKGROUND: Recently, the second-generation tyrosine kinase inhibitors dasatinib and nilotinib have emerged as alternative treatments in patients with chronic myeloid leukemia (CML) who are resistant to or intolerant of imatinib. OBJECTIVE: This article aimed to assess the cost utility and budget impact of using dasatinib or nilotinib, rather than high-dose (800-mg/d) imatinib, in patients with chronic phase (CP) CML who are resistant to standard-dose (400-mg/d) imatinib in Thailand. METHODS: A Markov simulation model was developed and used to estimate the lifetime costs and outcomes of treating patients aged ≥38 years with CP-CML. The efficacy parameters were synthesized from a systematic review. Utilities using the European Quality of Life-5 Dimensions tool and costs were obtained from the Thai CML population. Costs and outcomes were compared and presented as the incremental cost-effectiveness ratio in 2011 Thai baht (THB) per quality-adjusted life year (QALY) gained. One-way and probabilistic sensitivity analyses were performed to estimate parameter uncertainty. RESULTS: From a societal perspective, treatment with dasatinib was found to yield more QALYs (2.13) at a lower cost (THB 1,631,331) per person than high-dose imatinib. Nilotinib treatment was also found to be more cost-effective than high-dose imatinib, producing an incremental cost-effectiveness ratio of THB 83,328 per QALY gained. This treatment option also resulted in the highest number of QALYs gained of all of the treatment options. The costs of providing dasatinib, nilotinib, and high-dose imatinib were estimated at THB 5 billion, THB 6 billion, and THB 7 billion, respectively. CONCLUSIONS: Treatment with dasatinib or nilotinib is likely to be more cost-effective than treatment with high-dose imatinib in CP-CML patients who do not respond positively to standard-dose imatinib in the Thai context. Dasatinib was found to be more cost-effective than nilotinib.

Variation of health-related quality of life assessed by caregivers and patients affected by severe childhood infections.

BACKGROUND: The agreement between self-reported and proxy measures of health status in ill children is not well established. This study aimed to quantify the variation in health-related quality of life (HRQOL) derived from young patients and their carers using different instruments. METHODS: A hospital-based cross-sectional survey was conducted between August 2010 and March 2011. Children with meningitis, bacteremia, pneumonia, acute otitis media, hearing loss, chronic lung disease, epilepsy, mild mental retardation, severe mental retardation, and mental retardation combined with epilepsy, aged between five to 14 years in seven tertiary hospitals were selected for participation in this study. The Health Utilities Index Mark 2 (HUI2), and Mark 3 (HUI3), and the EuroQoL Descriptive System (EQ-5D) and Visual Analogue Scale (EQ-VAS) were applied to both paediatric patients (self-assessment) and caregivers (proxy-assessment). RESULTS: The EQ-5D scores were lowest for acute conditions such as meningitis, bacteremia, and pneumonia, whereas the HUI3 scores were lowest for most chronic conditions such as hearing loss and severe mental retardation. Comparing patient and proxy scores (n = 74), the EQ-5D exhibited high correlation (r = 0.77) while in the HUI2 and HUI3 patient and caregiver scores were moderately correlated (r = 0.58 and 0.67 respectively). The mean difference between self and proxy-assessment using the HUI2, HUI3, EQ-5D and EQ-VAS scores were 0.03, 0.05, -0.03 and -0.02, respectively. In hearing-impaired and chronic lung patients the self-rated HRQOL differed significantly from their caregivers. CONCLUSIONS: The use of caregivers as proxies for measuring HRQOL in young patients affected by pneumococcal infection and its sequelae should be employed with caution. Given the high correlation between instruments, each of the HRQOL instruments appears acceptable apart from the EQ-VAS which exhibited low correlation with the others.

Cost-utility analysis of 10- and 13-valent pneumococcal conjugate vaccines: protection at what price in the Thai context?

OBJECTIVE: This study aims to evaluate the costs and outcomes of offering the 10-valent pneumococcal conjugate vaccine (PCV10) and 13-valent pneumococcal conjugate vaccine (PCV13) in Thailand compared to the current situation of no PCV vaccination. METHODS: Two vaccination schedules were considered: two-dose primary series plus a booster dose (2+1) and three-dose primary series plus a booster dose (3+1). A cost-utility analysis was conducted using a societal perspective. A Markov simulation model was used to estimate the relevant costs and health outcomes for a lifetime horizon. Costs were collected and values were calculated for the year 2010. The results were reported as incremental cost-effectiveness ratios (ICERs) in Thai Baht (THB) per quality adjusted life year (QALY) gained, with future costs and outcomes being discounted at 3% per annum. One-way sensitivity analysis and probabilistic sensitivity analysis using a Monte Carlo simulation were performed to assess parameter uncertainty. RESULTS: Under the base case-scenario of 2+1 dose schedule and a five-year protection, without indirect vaccine effects, the ICER for PCV10 and PCV13 were THB 1,368,072 and THB 1,490,305 per QALY gained, respectively. With indirect vaccine effects, the ICER of PCV10 was THB 519,399, and for PCV13 was THB 527,378. The model was sensitive to discount rate, the change in duration of vaccine protection and the incidence of pneumonia for all age groups. CONCLUSIONS: At current prices, PCV10 and PCV13 are not cost-effective in Thailand. Inclusion of indirect vaccine effects substantially reduced the ICERs for both vaccines, but did not result in cost effectiveness.