Cost-Utility and Budget Impact Analysis of Biosimilar Trastuzumab for Early-Stage HER2- Positive Breast Cancer in Thailand: An Updated Evaluation Supporting Expanded Access

Cost-Utility and Budget Impact Analysis of Biosimilar Trastuzumab for Early-Stage HER2- Positive Breast Cancer in Thailand: An Updated Evaluation Supporting Expanded Access | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Cost-Utility and Budget Impact Analysis of Biosimilar Trastuzumab for Early-Stage HER2- Positive Breast Cancer in Thailand: An Updated Evaluation Supporting Expanded Access Surasit Lochid-amnuay, Ronnachai Kongsakon This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-7344634/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 29 Jan, 2026 Read the published version in BMC Health Services Research → Version 1 posted 9 You are reading this latest preprint version Abstract Background Trastuzumab is an established adjuvant therapy for early-stage HER2-positive breast cancer. Previous studies in Thailand demonstrated its cost-effectiveness, but earlier evaluations did not account for trastuzumab-related cardiac adverse events, costs of HER2 and hormone receptor testing, or the budgetary implications of expanding treatment eligibility. This updated economic evaluation incorporates biosimilar drug pricing, the clinical and economic burden of cardiotoxicity, and diagnostic testing costs, and assesses the impact of expanding access to patients with node-negative tumors larger than 2 cm and ER/PR-negative status. Methods A cost-utility analysis using a Markov model was conducted from a societal perspective over a lifetime horizon, comparing trastuzumab plus paclitaxel with paclitaxel monotherapy. Updated costs, transition probabilities for disease progression and cardiac events, and utility weights were applied. Direct medical, direct non-medical, and indirect costs were included, adjusted to 2024 Thai Baht (THB), with costs and quality-adjusted life years (QALYs) discounted at 3% annually. A budget impact analysis estimated the incremental cost of expanding reimbursement criteria to the additional eligible subgroup. Results Trastuzumab plus paclitaxel resulted in higher lifetime costs (THB 989,794 vs. THB 606,142) and greater health benefits (12.69 vs. 8.10 QALYs) than paclitaxel alone, yielding an incremental cost-effectiveness ratio (ICER) of THB 83,520 per QALY gained, well below Thailand’s cost-effectiveness threshold of THB 160,000 per QALY. Incorporating cardiac toxicity and diagnostic testing costs had minimal impact on ICER, reflecting the low incidence and reversibility of cardiotoxicity. The projected annual budget impact of expanding coverage to the additional patient subgroup was THB 53.9 million, representing a modest increase relative to expected clinical benefits. Conclusions Biosimilar trastuzumab remains a cost-effective adjuvant therapy for early-stage HER2-positive breast cancer in Thailand, even after accounting for cardiac adverse events and diagnostic testing costs. The findings support expanding reimbursement to high-risk node-negative patients with ER/PR-negative tumors larger than 2 cm, consistent with value-based policy expansion and efficient use of healthcare resources. Trastuzumab Biosimilar Cost-utility analysis Cardiac toxicity HER2-positive breast cancer Budget impact Expanded access Thailand Figures Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Introduction Breast cancer is a leading cause of morbidity and mortality among women worldwide and is currently the most frequently diagnosed malignancy among women in Thailand. According to GLOBOCAN 2022, the age-standardized incidence and mortality rates for breast cancer in Thailand are 37.4 and 11.8 per 100,000 women, respectively, indicating a sustained increase in disease burden over recent decades [1]. Although advancements in screening, early detection, and systemic therapies have improved survival outcomes, breast cancer continues to place a considerable clinical and economic burden on the Thai healthcare system. In particular, managing metastatic disease requires prolonged, resource-intensive, and often costly treatment, which may limit patient access and strain available healthcare resources [2]. Among breast cancer subtypes, human epidermal growth factor receptor 2 (HER2)-positive tumors account for approximately 15–20% of cases. These tumors typically exhibit more aggressive biological behavior, higher recurrence rates, and poorer survival compared with HER2-negative disease [3–5]. The advent of HER2-targeted therapies has markedly improved outcomes for this patient group. Trastuzumab, a recombinant humanized monoclonal antibody targeting the extracellular domain of the HER2 protein, has demonstrated substantial improvements in disease-free survival (DFS) and overall survival (OS) when used in combination with chemotherapy for early-stage HER2-positive breast cancer [6, 7]. In Thailand, trastuzumab was added to the National List of Essential Medicines (NLEM) in 2014 based on evidence of clinical efficacy and cost-effectiveness in patients with node-positive disease. Since then, it has been reimbursed under the Universal Coverage Scheme (UCS) and other public insurance programs for a defined subset of early-stage patients [8]. However, the original economic evaluation that informed this decision did not consider several important factors. First, while trastuzumab is generally well tolerated, it is associated with a risk of cardiotoxicity, including asymptomatic reductions in left ventricular ejection fraction (LVEF) and, less commonly, symptomatic congestive heart failure. The monitoring and management of these adverse events require additional healthcare resources and incur extra costs, which were not included in earlier models. Second, previous evaluations did not account for the costs of diagnostic testing essential for treatment selection. Determining HER2 status and hormone receptor (HR) expression through methods such as immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH) incurs nontrivial expenses that vary across healthcare facilities [9, 10]. Third, the pricing context has changed substantially with the introduction of biosimilar trastuzumab in Thailand, resulting in more than a 60% price reduction compared to the originator product, which has significant implications for cost-effectiveness. In parallel, clinical practice and policy discussions in Thailand have considered whether eligibility for trastuzumab should be broadened to include other high-risk subgroups. One such group is patients with node-negative tumors > 2 cm and negative hormone receptor expression (ER/PR-negative), who have been excluded from reimbursement but may still derive substantial clinical benefit from HER2-targeted therapy [11]. Expanding access to this population could improve outcomes but would also increase overall healthcare expenditure. This study provides an updated economic evaluation of trastuzumab as adjuvant therapy for early-stage HER2-positive breast cancer in Thailand. Specifically, it reassesses the cost-utility of trastuzumab plus paclitaxel versus paclitaxel alone using updated parameters that incorporate biosimilar pricing, cardiac adverse event costs, and diagnostic testing expenses. It also estimates the budgetary implications of expanding coverage to include node-negative, ER/PR-negative tumors > 2 cm. The findings aim to inform evidence-based policy decisions within Thailand’s national health insurance framework. Methods Study design and overview This study was a model-based economic evaluation assessing the cost-utility and budgetary impact of trastuzumab in combination with paclitaxel compared with paclitaxel alone as adjuvant therapy for early-stage HER2-positive breast cancer in Thailand. The analysis was undertaken from a societal perspective over a lifetime horizon, following the methodological framework outlined in the Thai Health Technology Assessment (HTA) guidelines[12]. An updated Markov model, adapted from a previously published Thai evaluation, was used to estimate total costs, health outcomes in quality-adjusted life years (QALYs), and incremental cost-effectiveness ratios (ICERs). The model incorporated health state transitions, costs, and utilities relevant to the Thai healthcare context. In addition, a five-year budget impact analysis was performed to evaluate the fiscal implications of expanding reimbursement criteria to include additional eligible patient subgroups. Model structure A cohort-based Markov model, adapted from a previously published Thai economic evaluation of trastuzumab [8], was developed to simulate the disease trajectory of women with early-stage HER2-positive breast cancer over their lifetime. The model comprised three mutually exclusive health states: disease-free, metastatic breast cancer, and death. For patients receiving trastuzumab, a sub-health state for cardiac adverse events, defined as congestive heart failure (CHF), was incorporated within the disease-free state to capture the potential impact of cardiotoxicity. The structure of the Markov model, including the health states and possible transitions, is illustrated in Fig. 1. The model cycle length was three weeks, consistent with the chemotherapy administration schedule, and transitions between health states were modeled until all patients had died. The simulated cohort entered the model at age 50 years, reflecting the median age at diagnosis of breast cancer in Thailand. Target population The study population comprised women with early-stage HER2-positive breast cancer eligible for adjuvant therapy, with preserved cardiac function (left ventricular ejection fraction ≥ 50%). Two scenarios were evaluated: (1) the base-case scenario representing the current reimbursement criteria (node-positive disease) and (2) an expanded-access scenario including node-negative patients with tumors > 2 cm and ER/PR-negative status. Transition probabilities Transition probabilities for health state changes were primarily based on Perez et al. [13], representing the most recent long-term follow-up data for trastuzumab combined with adjuvant chemotherapy from a pooled analysis of the NCCTG N9831 and NSABP B-31 trials. The number of disease-free patients was reported annually for up to four years, enabling calculation of transition probabilities from disease-free to metastatic disease during the initial follow-up period. For years beyond the fifth, the annual metastatic recurrence rate was sourced from the Early Breast Cancer Trialists’ Collaborative Group [14], while hazard ratios from Perez et al. [13], were applied to estimate transition probabilities from year six onward. The probability of progression from metastatic breast cancer to death was obtained from Slamon et al. [15]. Cardiac toxicity parameters were also derived from Slamon et al., which reported approximately a 2% incidence of congestive heart failure among trastuzumab-treated patients. The model structure and all parameter inputs were reviewed and approved by clinical and health economics experts during formal validation meetings prior to finalization. Cost and utility inputs The analysis included direct medical, direct non-medical, and indirect costs, where applicable. Direct medical costs were defined as healthcare expenses directly related to breast cancer treatment, including medication acquisition costs obtained from the reference prices of the Drugs and Medical Supplies Information Center, Ministry of Public Health [16]. Drug acquisition costs reflected biosimilar trastuzumab prices available through Thailand’s national procurement system. Costs for HER2 and hormone receptor testing (HER2/IHC), echocardiography, and cardiac monitoring were sourced from Thai standard costing databases [17], with biomarker testing costs calculated as the mean unit cost from the three hospitals included in this study. Inpatient service charges were derived from the Thai Diagnosis-Related Group (DRG) reimbursement rate. Direct non-medical costs included transportation and additional meal expenses, and indirect costs were obtained from the Thai Standard Cost List for Health Technology Assessment [17] (Table 1 ). All costs were inflated to 2024 Thai Baht using the medical consumer price index Table 1 Model input parameters Parameters Mean Standard error Distribution Reference Transition probability parameters Adjuvant therapy of trastuzumab and paclitaxel Disease free to metastatic year 1 0.0016 0.00003 Beta Perez et al. [13] Disease free to metastatic year 2 0.0030 0.0001 Beta Perez et al. [13] Disease free to metastatic year 3 0.0028 0.0001 Beta Perez et al. [13] Disease free to metastatic year 4 0.0015 0.00004 Beta Perez et al. [13] Disease free to metastatic year 5 0.0015 0.00005 Beta Perez et al. [13] Disease free to metastatic year 6–9 0.0014 0.0014 Beta Early Breast Cancer Trialists’ Collaborative Group [14] Disease free to metastatic year 10 onwards 0.0010 0.0010 Beta Early Breast Cancer Trialists’ Collaborative Group [14] Disease free to death 0.0010 0.00003 Beta Perez et al. [13] Metastatic to death 0.0223 0.00060 Beta Slamon et al. [15] Paclitaxel alone Disease free to metastatic year 1 0.0027 0.0001 Beta Perez et al. [13] Disease free to metastatic year 2 0.0055 0.0001 Beta Perez et al. [13] Disease free to metastatic year 3 0.0054 0.0001 Beta Perez et al. [13] Disease free to metastatic year 4 0.0040 0.0001 Beta Perez et al. [13] Disease free to metastatic year 5 0.0040 0.0001 Beta Perez et al. [13] Disease free to metastatic year 6–9 0.0028 0.0027 Beta Early Breast Cancer Trialists’ Collaborative Group [14] Disease free to metastatic year 10 onwards 0.0019 0.0019 Beta Early Breast Cancer Trialists’ Collaborative Group [14] Disease free to death 0.0223 0.0006 Beta Perez et al. [13] Metastatic to death 0.0223 0.00060 Beta Slamon et al. [15] Cardiac event Rate of Cardiac event in trastuzumab 0.0011 0.00003 Beta Slamon et al. [15] Direct medical cost Trastuzumab: first dose 5,246.79 524.68 Gamma DMSIC. [16] Trastuzumab: subsequent dose 3,935.09 393.51 Gamma DMSIC. [16] Paclitaxel 3,697.51 369.75 Gamma DMSIC. [16] Capecitabine 4,092.48 409.25 Gamma DMSIC. [16] IPD care 1,581.83 158.18 Gamma Riewpaiboon A. [17] OPD visit 368.44 36.84 Gamma Riewpaiboon A. [17] Admission 15,644.00 1,564.40 Gamma Riewpaiboon A. [17] CT (upper abdomen) 5,332.29 533.22 Gamma Riewpaiboon A. [17] Bone scan 1,952.87 195.29 Gamma Riewpaiboon A. [17] Liver function test 71.45 7.14 Gamma Riewpaiboon A. [17] Chest x-ray 106.65 10.66 Gamma Riewpaiboon A. [17] CBC test 129.04 12.90 Gamma Riewpaiboon A. [17] Echocardiography 4,318.17 431.81 Gamma Riewpaiboon A. [17] Cardiac monitoring 863.85 86.38 Gamma Riewpaiboon A. [17] Biomarker test (HER-2/IHS) 13,033 1,303.30 Gamma Unit cost* Direct non-medical cost Travelling cost 185.59 15.10 Gamma Riewpaiboon A. [17] Cost for food 68.36 6.97 Gamma Riewpaiboon A. [17] Health utility Disease Free (Age) 45–59 0.939 0.0018 Beta Thai National Health Examination Survey [18] 60–69 0.921 0.0023 Beta Thai National Health Examination Survey [18] 70–79 0.878 0.0029 Beta Thai National Health Examination Survey [18] 80 or older 0.843 0.0062 Beta Thai National Health Examination Survey [18] CHF state 0.8350 0.1378 Beta Skedgel et al. [20] Metastatic 0.6000 0.240 Beta Hornberger et al. [19] DMSIC : Drugs and Medical Supplies Information Center, Ministry of Public Health *Unit costs are calculated as the average from three hospitals included in the study Quality-adjusted life years (QALYs) were calculated by multiplying life years by utility weights, where 0 represented death and 1 represented perfect health. Utility values for non-metastatic breast cancer were assigned by age group based on EQ-5D data from the Thai National Health Examination Survey [18]. Due to the limited availability of Thai utility data for metastatic breast cancer, utility values for metastatic states were obtained from Hornberger et al. [19], and values for CHF were taken from Skedgel et al. [20]. Within the model, utility weights for each health state were multiplied by the proportion of the cohort in that state during each three-week cycle, with results aggregated over the lifetime horizon. In accordance with Thai HTA guidelines [12], both costs and QALYs were discounted at an annual rate of 3%. Sensitivity analysis Uncertainty in model parameters was explored using probabilistic sensitivity analysis (PSA) with 1,000 Monte Carlo simulations. Input parameters were sampled from appropriate probability distributions: beta for probabilities and utilities, and gamma for costs. PSA results were presented as cost-effectiveness acceptability curves (CEACs) and cost-effectiveness planes. One-way sensitivity analyses were also performed to identify parameters exerting the greatest influence on model outcomes. Budget impact analysis A five-year budget impact analysis was undertaken from the payer’s perspective to estimate the incremental cost of expanding trastuzumab access to patients with node-negative tumors > 2 cm and ER/PR-negative status. The number of eligible patients was estimated using national cancer registry data, HER2 positivity rates, and insurance enrollment figures. Annual costs included drug acquisition and laboratory testing. The incremental budget impact was calculated for both the current reimbursement policy and the proposed expanded-access scenario, and results were reported in Thai Baht (THB). Base-case cost-utility analysis In the base-case scenario, adjuvant trastuzumab in combination with paclitaxel was associated with higher lifetime costs but yielded substantially greater health benefits compared with paclitaxel monotherapy. The mean lifetime cost per patient was THB 989,794 in the trastuzumab arm and THB 606,142 in the paclitaxel-only arm. Patients receiving trastuzumab achieved 12.69 quality-adjusted life years (QALYs) versus 8.10 QALYs for paclitaxel alone, corresponding to an incremental gain of 4.59 QALYs. This translated into an incremental cost-effectiveness ratio (ICER) of THB 83,520 per QALY gained, which is well below the Thai cost-effectiveness threshold of THB 160,000 per QALY. These results are summarized in Table 2 . Table 2 Base-case cost-utility results Outcome Trastuzumab + Paclitaxel Paclitaxel alone Incremental difference Cost (THB) 989,794 606,142 383,653 Life years (years) 14.12 9.11 5.01 Quality-adjusted life years (QALYs) 12.69 8.10 4.59 ICER (THB per QALY gained) – – 83,520 Note: ICER = Incremental cost-effectiveness ratio; QALY = Quality-adjusted life year; THB = Thai Baht. The improved cost-effectiveness relative to previous Thai evaluations is primarily attributable to the introduction of biosimilar trastuzumab via national pooled procurement, which has reduced the unit price by more than 60% compared with the originator product. This substantial price reduction has markedly lowered the incremental cost per patient, strengthening the economic justification for continued inclusion of trastuzumab in the national reimbursement framework. Incorporating the costs of HER2 and hormone receptor testing had only a modest impact on the ICER. Although these diagnostics are essential for ensuring appropriate patient selection, their contribution to total treatment cost was relatively small in the context of biosimilar pricing. Similarly, inclusion of the costs associated with cardiac adverse event management, based on an estimated 2% incidence of congestive heart failure (CHF) among trastuzumab-treated patients, had minimal influence on the ICER. This reflects both the low frequency and the typically reversible nature of such events when appropriately monitored and managed. Sensitivity analysis Probabilistic sensitivity analysis (PSA) confirmed the robustness of the base-case findings, with more than 90% of simulations indicating cost-effectiveness at a willingness-to-pay (WTP) threshold of THB 100,000 per QALY, and the vast majority falling below the official Thai threshold of THB 160,000 per QALY. The incremental cost-effectiveness plane (Fig. 2) presents the scatter plot of 1,000 Monte Carlo simulations for trastuzumab versus paclitaxel alone. Most simulated ICER points lie below the Thai cost-effectiveness threshold of THB 160,000 per QALY, indicating a high probability of cost-effectiveness. The cost-effectiveness acceptability curve (Fig. 3) illustrates the probability of trastuzumab being cost-effective across a range of WTP thresholds; at THB 160,000 per QALY, the probability exceeds 95%, reinforcing the favorable economic profile of the intervention. The results of the one-way sensitivity analysis are depicted in the tornado diagram (Fig. 4), which ranks model parameters according to their impact on the ICER. The most influential parameters were the transition probabilities from the disease-free to metastatic state in later years for both the trastuzumab and paclitaxel arms, followed by the annual cost of trastuzumab. Other parameters with notable influence included the cost of CT scans, the utility weight assigned to metastatic breast cancer, and the costs of outpatient visits and capecitabine. In contrast, variation in the probability of death from the disease-free state in the trastuzumab arm exerted minimal influence on the ICER. Across all plausible parameter ranges, trastuzumab remained cost-effective, underscoring the stability of the model’s conclusions. Budget impact analysis Under current reimbursement criteria restricted to node-positive disease, the annual number of eligible patients was estimated at 4,342 (3,277 prevalent and 1,065 incident cases) (Table 3 ). Expanding coverage to include node-negative patients with tumors > 2 cm and ER/PR-negative status would increase the eligible population by approximately 963 patients annually (727 prevalent and 236 incident cases). In the first year following policy expansion, the total projected cost of trastuzumab treatment and associated laboratory testing was THB 914.8 million, comprising THB 862.6 million for drug acquisition and THB 52.2 million for diagnostics. In subsequent years, when only incident cases would require treatment, the annual total cost was projected at THB 297.3 million (THB 280.4 million for drugs and THB 17.0 million for diagnostics). Compared with the current policy, the expanded-access scenario would result in incremental costs of THB 53.9 million in Year 1 and THB 24.5 million annually thereafter (Table 3 , Fig. 5). Table 3 Five-Year Budget Impact of Adjuvant Trastuzumab Under Current and Expanded-Access Scenarios (Payer Perspective) Year Eligible Patients (n) Drug Acquisition Cost (THB million) Diagnostic Testing Cost (THB million) Total Annual Cost (THB million) Incremental Cost vs. Current Policy (THB million) Current Reimbursement Policy (Node-positive only) 1 4,342 (3,277 prevalent, 1,065 incident) 808.7 49.6 858.3 – 2 1,065 (incident only) 256.9 15.9 272.8 – 3 1,065 256.9 15.9 272.8 – 4 1,065 256.9 15.9 272.8 – 5 1,065 256.9 15.9 272.8 – Expanded Access (+ Node-negative > 2 cm, ER/PR–negative) 1 5,305 (4,004 prevalent, 1,301 incident) 862.6 52.2 914.8 + 53.9 2 1,301 (incident only) 280.4 17.0 297.3 + 24.5 3 1,301 280.4 17.0 297.3 + 24.5 4 1,301 280.4 17.0 297.3 + 24.5 5 1,301 280.4 17.0 297.3 + 24.5 Notes: All costs are in 2024 Thai Baht (THB), adjusted using the medical consumer price index. Diagnostic costs include HER2 and hormone receptor testing, echocardiography, and cardiac monitoring. The expanded-access scenario assumes full uptake among eligible node-negative patients with tumors > 2 cm and ER/PR-negative status. Although the additional expenditure is substantial in absolute terms, the reduced per-patient cost facilitated by biosimilar procurement (THB 215,448 on average compared with THB 475,921 in earlier analyses) significantly mitigates the fiscal impact. When considered alongside the favorable cost-effectiveness profile and potential clinical benefit in high-risk node-negative patients, these findings support the financial feasibility of expanding trastuzumab access within the Thai Universal Coverage Scheme. Discussion This study evaluated the cost-effectiveness and budget impact of adjuvant trastuzumab combined with paclitaxel versus paclitaxel monotherapy for early-stage HER2-positive breast cancer in Thailand. The updated analysis addressed key gaps in previous evaluations by incorporating the costs of HER2 and hormone receptor testing, as well as the clinical and economic consequences of trastuzumab-induced cardiac toxicity. The use of current biosimilar pricing ensures that the results reflect real-world procurement conditions under Thailand’s national healthcare system. The results confirmed that trastuzumab remains highly cost-effective, with an incremental cost-effectiveness ratio (ICER) of 83,520 Thai Baht (THB) per quality-adjusted life year (QALY) gained, well below the national threshold of 160,000 THB per QALY (ref). Compared with earlier analyses based on originator pricing, this ICER represents a marked improvement, primarily due to a 68% reduction in unit cost following the adoption of biosimilar trastuzumab through centralized procurement. Cardiac adverse events, which occur in approximately 2% of patients receiving trastuzumab [21, 22], and the inclusion of diagnostic testing costs had only a minimal effect on overall QALYs and total costs, indicating that these factors do not undermine the intervention’s economic value. This enhances the external validity of the model by aligning it more closely with routine clinical practice. The expanded coverage scenario, which includes node-negative patients with tumors larger than 2 centimeters and who are ER/PR-negative, also demonstrated cost-effectiveness. The ICER for this subgroup remained below the national threshold, and probabilistic sensitivity analysis indicated a greater than 90% probability of cost-effectiveness across plausible parameter ranges. This finding is notable because such patients were previously excluded from reimbursement on fiscal grounds, despite having a higher risk of recurrence compared with other node-negative groups. From a budgetary perspective, extending coverage is projected to increase annual public expenditure by approximately 53.92 million THB. However, biosimilar pricing has reduced the average treatment cost per patient to 215,448 THB, compared with 475,921 THB in earlier studies [8]. The total five-year budget impact for both current and expanded patient groups is estimated at 297.34 million THB annually, a level that appears manageable within the Thai Universal Health Coverage (UHC) framework. These results suggest that expanding reimbursement would deliver substantial health gains at an affordable budgetary cost, representing an efficient allocation of limited healthcare resources. Maximising the value of expanded coverage requires clearly defined eligibility criteria incorporating HER2 status, tumour size thresholds, and hormone receptor status. Establishing these parameters will facilitate appropriate patient selection, ensure equitable access, and optimise resource allocation. Furthermore, continued price negotiations for biosimilar trastuzumab and the introduction of financial support mechanisms for diagnostic testing could sustain long-term affordability and minimise financial barriers to treatment. Conclusion This updated economic evaluation provides robust and policy-relevant evidence that adjuvant biosimilar trastuzumab, when administered in combination with paclitaxel, is a cost-effective intervention for early-stage HER2-positive breast cancer in Thailand. By incorporating diagnostic testing costs and the clinical and economic implications of trastuzumab-associated cardiac toxicity, the analysis offers a more comprehensive and realistic assessment of value under routine care conditions. The findings demonstrate that expanding reimbursement to include high-risk node-negative patients with tumours larger than 2 cm and ER/PR-negative status meets the national cost-effectiveness threshold, with only a modest projected increase in public expenditure. This expansion is further facilitated by a substantial reduction in per-patient treatment costs following biosimilar procurement. To translate this evidence into practice, policymakers should update national coverage guidelines to reflect current cost-effectiveness data and clearly define eligibility criteria based on HER2 status, tumour size, and hormone receptor profile. Continued price negotiations for biosimilar trastuzumab, coupled with targeted financial support for diagnostic testing, could strengthen affordability and reduce barriers to equitable access. Overall, this study supports evidence-informed updates to Thailand’s Universal Health Coverage policy. Expanding trastuzumab access in this manner would optimise the allocation of limited healthcare resources while advancing the national objective of delivering equitable, high-quality cancer care. Declarations Ethics approval and consent to participate Not applicable. This study used secondary data from published sources and national databases; no human participants were directly involved. Consent for publication Not applicable. Availability of data and materials The datasets generated and/or analysed during the current study are available from the corresponding author on reasonable request. Competing interests The authors declare that they have no competing interests. Funding This research received no specific grant from any funding agency in the public, commercial, or not-for-profit sectors. Authors’ contributions SL conceived and designed the study, developed the economic model, performed the analysis, and drafted the manuscript. RK contributed to the study design, provided clinical input for model parameters, validated results, and critically revised the manuscript. Both authors read and approved the final manuscript. 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Cite Share Download PDF Status: Published Journal Publication published 29 Jan, 2026 Read the published version in BMC Health Services Research → Version 1 posted Editorial decision: Revision requested 15 Dec, 2025 Reviews received at journal 10 Dec, 2025 Reviewers agreed at journal 10 Dec, 2025 Reviews received at journal 25 Aug, 2025 Reviewers agreed at journal 20 Aug, 2025 Reviewers invited by journal 19 Aug, 2025 Editor assigned by journal 12 Aug, 2025 Submission checks completed at journal 12 Aug, 2025 First submitted to journal 11 Aug, 2025 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-7344634","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":499061630,"identity":"e0428da5-d52a-4341-bf80-5bb387b5544c","order_by":0,"name":"Surasit Lochid-amnuay","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA8UlEQVRIiWNgGAWjYBACPgYGNoYENjjfBsY4gFMLG5qWNCidQEALA0LLYSK0sDc/e/CgzC7aXCL5mQTDn/P2BgeYH35g/HEHtxaeY+YGCeeSc3fOSDOTYGy7nbjhAJuxBEPCM9xaJHLYJBLbmHM33EgAamm4nWBwgMEM6LDDhLTUA7WkfwM67BzQYezfiNFyGKglx0yCge0A44YDPARs4TlmJpFw7njuhjNvii0Y25ITZx7mKZZISMOthR8YYpI/yqpzNxxP33iD4Y+dPd/x9o0fPtjg1oIMWKT/gChmIE4gSgNQ7QciFY6CUTAKRsEIAwBpcFL97Rc68QAAAABJRU5ErkJggg==","orcid":"","institution":"Department of Health Consumer Protection and Pharmacy Administration, Faculty of Pharmacy, Silpakorn University","correspondingAuthor":true,"prefix":"","firstName":"Surasit","middleName":"","lastName":"Lochid-amnuay","suffix":""},{"id":499061631,"identity":"43ea6a98-a829-4bc6-9d56-5596fd2f858e","order_by":1,"name":"Ronnachai Kongsakon","email":"","orcid":"","institution":"Chulabhorn Royal Academy","correspondingAuthor":false,"prefix":"","firstName":"Ronnachai","middleName":"","lastName":"Kongsakon","suffix":""}],"badges":[],"createdAt":"2025-08-11 09:23:25","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-7344634/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-7344634/v1","draftVersion":[],"editorialEvents":[{"content":"https://doi.org/10.1186/s12913-026-14094-0","type":"published","date":"2026-01-29T15:59:33+00:00"}],"editorialNote":"","failedWorkflow":false,"files":[{"id":88951697,"identity":"85adbc7c-28ac-4c5c-9690-2bb3b7e39dfa","added_by":"auto","created_at":"2025-08-13 05:54:40","extension":"jpg","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":47753,"visible":true,"origin":"","legend":"\u003cp\u003eLegend not included with this version\u003c/p\u003e","description":"","filename":"Figure1.ThehealthstatesincludedintheMarkovmodel.jpg","url":"https://assets-eu.researchsquare.com/files/rs-7344634/v1/62677ecda58ce59567231e32.jpg"},{"id":88952188,"identity":"b99d8b8b-be17-43f7-997d-912053aaab52","added_by":"auto","created_at":"2025-08-13 06:02:41","extension":"jpg","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":104774,"visible":true,"origin":"","legend":"\u003cp\u003eLegend not included with this version\u003c/p\u003e","description":"","filename":"Figure2.CEPlane.jpg","url":"https://assets-eu.researchsquare.com/files/rs-7344634/v1/4522caaab76998845a78e263.jpg"},{"id":88951701,"identity":"5cd5aad5-785c-448e-8ad6-102ae222e079","added_by":"auto","created_at":"2025-08-13 05:54:41","extension":"jpg","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":84079,"visible":true,"origin":"","legend":"\u003cp\u003eLegend not included with this version\u003c/p\u003e","description":"","filename":"Figure3.Acceptabilitycurve.jpg","url":"https://assets-eu.researchsquare.com/files/rs-7344634/v1/26a36e86e404e9e875cb5184.jpg"},{"id":88951700,"identity":"bca0eb24-2f75-4c7d-a108-8701e1e289dd","added_by":"auto","created_at":"2025-08-13 05:54:41","extension":"jpg","order_by":4,"title":"Figure 4","display":"","copyAsset":false,"role":"figure","size":69017,"visible":true,"origin":"","legend":"\u003cp\u003eLegend not included with this version\u003c/p\u003e","description":"","filename":"Figure4.Tonododiagram.jpg","url":"https://assets-eu.researchsquare.com/files/rs-7344634/v1/7b8032d735970f2b21cd20fd.jpg"},{"id":88952884,"identity":"608e20a6-edf3-48de-8532-b56efe20c4b9","added_by":"auto","created_at":"2025-08-13 06:10:41","extension":"jpg","order_by":5,"title":"Figure 5","display":"","copyAsset":false,"role":"figure","size":87782,"visible":true,"origin":"","legend":"\u003cp\u003eLegend not included with this version\u003c/p\u003e","description":"","filename":"Figure5.Fiveyearbudgetimpactoftrastuzumabcurrentreimbursementcriteriavsexpandedaccessscenario.jpg","url":"https://assets-eu.researchsquare.com/files/rs-7344634/v1/e5e6c973fddcce6e2c679a80.jpg"},{"id":101690639,"identity":"aa479006-9550-47db-ad73-5665f9916b69","added_by":"auto","created_at":"2026-02-02 16:06:33","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":2282154,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-7344634/v1/c148addf-8fb7-4eec-bd7a-9997f5d4b458.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Cost-Utility and Budget Impact Analysis of Biosimilar Trastuzumab for Early-Stage HER2- Positive Breast Cancer in Thailand: An Updated Evaluation Supporting Expanded Access","fulltext":[{"header":"Introduction","content":"\u003cp\u003eBreast cancer is a leading cause of morbidity and mortality among women worldwide and is currently the most frequently diagnosed malignancy among women in Thailand. According to GLOBOCAN 2022, the age-standardized incidence and mortality rates for breast cancer in Thailand are 37.4 and 11.8 per 100,000 women, respectively, indicating a sustained increase in disease burden over recent decades [1]. Although advancements in screening, early detection, and systemic therapies have improved survival outcomes, breast cancer continues to place a considerable clinical and economic burden on the Thai healthcare system. In particular, managing metastatic disease requires prolonged, resource-intensive, and often costly treatment, which may limit patient access and strain available healthcare resources [2]. Among breast cancer subtypes, human epidermal growth factor receptor 2 (HER2)-positive tumors account for approximately 15\u0026ndash;20% of cases. These tumors typically exhibit more aggressive biological behavior, higher recurrence rates, and poorer survival compared with HER2-negative disease [3\u0026ndash;5]. The advent of HER2-targeted therapies has markedly improved outcomes for this patient group. Trastuzumab, a recombinant humanized monoclonal antibody targeting the extracellular domain of the HER2 protein, has demonstrated substantial improvements in disease-free survival (DFS) and overall survival (OS) when used in combination with chemotherapy for early-stage HER2-positive breast cancer [6, 7].\u003c/p\u003e\u003cp\u003eIn Thailand, trastuzumab was added to the National List of Essential Medicines (NLEM) in 2014 based on evidence of clinical efficacy and cost-effectiveness in patients with node-positive disease. Since then, it has been reimbursed under the Universal Coverage Scheme (UCS) and other public insurance programs for a defined subset of early-stage patients [8]. However, the original economic evaluation that informed this decision did not consider several important factors. First, while trastuzumab is generally well tolerated, it is associated with a risk of cardiotoxicity, including asymptomatic reductions in left ventricular ejection fraction (LVEF) and, less commonly, symptomatic congestive heart failure. The monitoring and management of these adverse events require additional healthcare resources and incur extra costs, which were not included in earlier models. Second, previous evaluations did not account for the costs of diagnostic testing essential for treatment selection. Determining HER2 status and hormone receptor (HR) expression through methods such as immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH) incurs nontrivial expenses that vary across healthcare facilities [9, 10]. Third, the pricing context has changed substantially with the introduction of biosimilar trastuzumab in Thailand, resulting in more than a 60% price reduction compared to the originator product, which has significant implications for cost-effectiveness.\u003c/p\u003e\u003cp\u003eIn parallel, clinical practice and policy discussions in Thailand have considered whether eligibility for trastuzumab should be broadened to include other high-risk subgroups. One such group is patients with node-negative tumors\u0026thinsp;\u0026gt;\u0026thinsp;2 cm and negative hormone receptor expression (ER/PR-negative), who have been excluded from reimbursement but may still derive substantial clinical benefit from HER2-targeted therapy [11]. Expanding access to this population could improve outcomes but would also increase overall healthcare expenditure.\u003c/p\u003e\u003cp\u003eThis study provides an updated economic evaluation of trastuzumab as adjuvant therapy for early-stage HER2-positive breast cancer in Thailand. Specifically, it reassesses the cost-utility of trastuzumab plus paclitaxel versus paclitaxel alone using updated parameters that incorporate biosimilar pricing, cardiac adverse event costs, and diagnostic testing expenses. It also estimates the budgetary implications of expanding coverage to include node-negative, ER/PR-negative tumors\u0026thinsp;\u0026gt;\u0026thinsp;2 cm. The findings aim to inform evidence-based policy decisions within Thailand\u0026rsquo;s national health insurance framework.\u003c/p\u003e"},{"header":"Methods","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e\u003ch2\u003eStudy design and overview\u003c/h2\u003e\u003cp\u003eThis study was a model-based economic evaluation assessing the cost-utility and budgetary impact of trastuzumab in combination with paclitaxel compared with paclitaxel alone as adjuvant therapy for early-stage HER2-positive breast cancer in Thailand. The analysis was undertaken from a societal perspective over a lifetime horizon, following the methodological framework outlined in the Thai Health Technology Assessment (HTA) guidelines[12].\u003c/p\u003e\u003cp\u003eAn updated Markov model, adapted from a previously published Thai evaluation, was used to estimate total costs, health outcomes in quality-adjusted life years (QALYs), and incremental cost-effectiveness ratios (ICERs). The model incorporated health state transitions, costs, and utilities relevant to the Thai healthcare context. In addition, a five-year budget impact analysis was performed to evaluate the fiscal implications of expanding reimbursement criteria to include additional eligible patient subgroups.\u003c/p\u003e\u003c/div\u003e\n\u003ch3\u003eModel structure\u003c/h3\u003e\n\u003cp\u003eA cohort-based Markov model, adapted from a previously published Thai economic evaluation of trastuzumab [8], was developed to simulate the disease trajectory of women with early-stage HER2-positive breast cancer over their lifetime. The model comprised three mutually exclusive health states: disease-free, metastatic breast cancer, and death. For patients receiving trastuzumab, a sub-health state for cardiac adverse events, defined as congestive heart failure (CHF), was incorporated within the disease-free state to capture the potential impact of cardiotoxicity. The structure of the Markov model, including the health states and possible transitions, is illustrated in Fig.\u0026nbsp;1. The model cycle length was three weeks, consistent with the chemotherapy administration schedule, and transitions between health states were modeled until all patients had died. The simulated cohort entered the model at age 50 years, reflecting the median age at diagnosis of breast cancer in Thailand.\u003c/p\u003e\n\u003ch3\u003eTarget population\u003c/h3\u003e\n\u003cp\u003eThe study population comprised women with early-stage HER2-positive breast cancer eligible for adjuvant therapy, with preserved cardiac function (left ventricular ejection fraction\u0026thinsp;\u0026ge;\u0026thinsp;50%). Two scenarios were evaluated: (1) the base-case scenario representing the current reimbursement criteria (node-positive disease) and (2) an expanded-access scenario including node-negative patients with tumors\u0026thinsp;\u0026gt;\u0026thinsp;2 cm and ER/PR-negative status.\u003c/p\u003e\n\u003ch3\u003eTransition probabilities\u003c/h3\u003e\n\u003cp\u003eTransition probabilities for health state changes were primarily based on Perez et al. [13], representing the most recent long-term follow-up data for trastuzumab combined with adjuvant chemotherapy from a pooled analysis of the NCCTG N9831 and NSABP B-31 trials. The number of disease-free patients was reported annually for up to four years, enabling calculation of transition probabilities from disease-free to metastatic disease during the initial follow-up period. For years beyond the fifth, the annual metastatic recurrence rate was sourced from the Early Breast Cancer Trialists\u0026rsquo; Collaborative Group [14], while hazard ratios from Perez et al. [13], were applied to estimate transition probabilities from year six onward. The probability of progression from metastatic breast cancer to death was obtained from Slamon et al. [15]. Cardiac toxicity parameters were also derived from Slamon et al., which reported approximately a 2% incidence of congestive heart failure among trastuzumab-treated patients. The model structure and all parameter inputs were reviewed and approved by clinical and health economics experts during formal validation meetings prior to finalization.\u003c/p\u003e\n\u003ch3\u003eCost and utility inputs\u003c/h3\u003e\n\u003cp\u003eThe analysis included direct medical, direct non-medical, and indirect costs, where applicable. Direct medical costs were defined as healthcare expenses directly related to breast cancer treatment, including medication acquisition costs obtained from the reference prices of the Drugs and Medical Supplies Information Center, Ministry of Public Health [16]. Drug acquisition costs reflected biosimilar trastuzumab prices available through Thailand\u0026rsquo;s national procurement system. Costs for HER2 and hormone receptor testing (HER2/IHC), echocardiography, and cardiac monitoring were sourced from Thai standard costing databases [17], with biomarker testing costs calculated as the mean unit cost from the three hospitals included in this study. Inpatient service charges were derived from the Thai Diagnosis-Related Group (DRG) reimbursement rate. Direct non-medical costs included transportation and additional meal expenses, and indirect costs were obtained from the Thai Standard Cost List for Health Technology Assessment [17] (Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e). All costs were inflated to 2024 Thai Baht using the medical consumer price index\u003c/p\u003e\u003cp\u003e\u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e\u003ccaption language=\"En\"\u003e\u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e\u003cdiv class=\"CaptionContent\"\u003e\u003cp\u003eModel input parameters\u003c/p\u003e\u003c/div\u003e\u003c/caption\u003e\u003ccolgroup cols=\"5\"\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e\u003cthead\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\"\u003e\u003cp\u003eParameters\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c2\"\u003e\u003cp\u003eMean\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c3\"\u003e\u003cp\u003eStandard error\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c4\"\u003e\u003cp\u003eDistribution\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c5\"\u003e\u003cp\u003eReference\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colspan=\"5\" nameend=\"c5\" namest=\"c1\"\u003e\u003cp\u003e\u003cem\u003eTransition probability parameters\u003c/em\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colspan=\"5\" nameend=\"c5\" namest=\"c1\"\u003e\u003cp\u003e\u003cem\u003eAdjuvant therapy of trastuzumab and paclitaxel\u003c/em\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eDisease free to metastatic year 1\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e0.0016\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e0.00003\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003eBeta\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003ePerez et al. [13]\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eDisease free to metastatic year 2\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e0.0030\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e0.0001\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003eBeta\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003ePerez et al. [13]\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eDisease free to metastatic year 3\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e0.0028\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e0.0001\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003eBeta\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003ePerez et al. [13]\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eDisease free to metastatic year 4\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e0.0015\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e0.00004\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003eBeta\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003ePerez et al. [13]\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eDisease free to metastatic year 5\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e0.0015\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e0.00005\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003eBeta\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003ePerez et al. [13]\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eDisease free to metastatic year 6\u0026ndash;9\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e0.0014\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e0.0014\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003eBeta\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003eEarly Breast Cancer Trialists\u0026rsquo; Collaborative Group [14]\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eDisease free to metastatic year 10 onwards\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e0.0010\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e0.0010\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003eBeta\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003eEarly Breast Cancer Trialists\u0026rsquo; Collaborative Group [14]\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eDisease free to death\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e0.0010\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e0.00003\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003eBeta\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003ePerez et al. [13]\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eMetastatic to death\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e0.0223\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e0.00060\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003eBeta\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003eSlamon et al. [15]\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cem\u003ePaclitaxel alone\u003c/em\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eDisease free to metastatic year 1\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e0.0027\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e0.0001\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003eBeta\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003ePerez et al. [13]\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eDisease free to metastatic year 2\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e0.0055\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e0.0001\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003eBeta\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003ePerez et al. [13]\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eDisease free to metastatic year 3\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e0.0054\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e0.0001\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003eBeta\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003ePerez et al. [13]\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eDisease free to metastatic year 4\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e0.0040\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e0.0001\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003eBeta\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003ePerez et al. [13]\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eDisease free to metastatic year 5\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e0.0040\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e0.0001\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003eBeta\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003ePerez et al. [13]\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eDisease free to metastatic year 6\u0026ndash;9\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e0.0028\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e0.0027\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003eBeta\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003eEarly Breast Cancer Trialists\u0026rsquo; Collaborative Group [14]\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eDisease free to metastatic year 10 onwards\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e0.0019\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e0.0019\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003eBeta\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003eEarly Breast Cancer Trialists\u0026rsquo; Collaborative Group [14]\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eDisease free to death\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e0.0223\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e0.0006\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003eBeta\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003ePerez et al. [13]\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eMetastatic to death\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e0.0223\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e0.00060\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003eBeta\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003eSlamon et al. [15]\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cem\u003eCardiac event\u003c/em\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eRate of Cardiac event in trastuzumab\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e0.0011\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e0.00003\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003eBeta\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003eSlamon et al. [15]\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colspan=\"5\" nameend=\"c5\" namest=\"c1\"\u003e\u003cp\u003e\u003cem\u003eDirect medical cost\u003c/em\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eTrastuzumab: first dose\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e5,246.79\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e524.68\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003eGamma\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003eDMSIC. [16]\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eTrastuzumab: subsequent dose\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e3,935.09\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e393.51\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003eGamma\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003eDMSIC. [16]\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003ePaclitaxel\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e3,697.51\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e369.75\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003eGamma\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003eDMSIC. [16]\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eCapecitabine\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e4,092.48\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e409.25\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003eGamma\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003eDMSIC. [16]\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eIPD care\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e1,581.83\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e158.18\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003eGamma\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003eRiewpaiboon A. [17]\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eOPD visit\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e368.44\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e36.84\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003eGamma\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003eRiewpaiboon A. [17]\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eAdmission\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e15,644.00\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e1,564.40\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003eGamma\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003eRiewpaiboon A. [17]\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eCT (upper abdomen)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e5,332.29\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e533.22\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003eGamma\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003eRiewpaiboon A. [17]\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eBone scan\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e1,952.87\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e195.29\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003eGamma\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003eRiewpaiboon A. [17]\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eLiver function test\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e71.45\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e7.14\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003eGamma\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003eRiewpaiboon A. [17]\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eChest x-ray\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e106.65\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e10.66\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003eGamma\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003eRiewpaiboon A. [17]\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eCBC test\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e129.04\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e12.90\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003eGamma\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003eRiewpaiboon A. [17]\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eEchocardiography\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e4,318.17\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e431.81\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003eGamma\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003eRiewpaiboon A. [17]\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eCardiac monitoring\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e863.85\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e86.38\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003eGamma\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003eRiewpaiboon A. [17]\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eBiomarker test (HER-2/IHS)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e13,033\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e1,303.30\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003eGamma\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003eUnit cost*\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cem\u003eDirect non-medical cost\u003c/em\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eTravelling cost\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e185.59\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e15.10\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003eGamma\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003eRiewpaiboon A. [17]\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eCost for food\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e68.36\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e6.97\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003eGamma\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003eRiewpaiboon A. [17]\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cem\u003eHealth utility\u003c/em\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eDisease Free (Age)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e45\u0026ndash;59\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e0.939\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e0.0018\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003eBeta\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003eThai National Health Examination Survey [18]\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e60\u0026ndash;69\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e0.921\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e0.0023\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003eBeta\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003eThai National Health Examination Survey [18]\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e70\u0026ndash;79\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e0.878\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e0.0029\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003eBeta\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003eThai National Health Examination Survey [18]\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e80 or older\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e0.843\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e0.0062\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003eBeta\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003eThai National Health Examination Survey [18]\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eCHF state\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e0.8350\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e0.1378\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003eBeta\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003eSkedgel et al. [20]\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eMetastatic\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e0.6000\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e0.240\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003eBeta\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003eHornberger et al. [19]\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/colgroup\u003e\u003ctfoot\u003e\u003ctr\u003e\u003ctd colspan=\"5\"\u003eDMSIC : Drugs and Medical Supplies Information Center, Ministry of Public Health\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd colspan=\"5\"\u003e*Unit costs are calculated as the average from three hospitals included in the study\u003c/td\u003e\u003c/tr\u003e\u003c/tfoot\u003e\u003c/table\u003e\u003c/div\u003e\u003c/p\u003e\u003cp\u003eQuality-adjusted life years (QALYs) were calculated by multiplying life years by utility weights, where 0 represented death and 1 represented perfect health. Utility values for non-metastatic breast cancer were assigned by age group based on EQ-5D data from the Thai National Health Examination Survey [18]. Due to the limited availability of Thai utility data for metastatic breast cancer, utility values for metastatic states were obtained from Hornberger et al. [19], and values for CHF were taken from Skedgel et al. [20]. Within the model, utility weights for each health state were multiplied by the proportion of the cohort in that state during each three-week cycle, with results aggregated over the lifetime horizon. In accordance with Thai HTA guidelines [12], both costs and QALYs were discounted at an annual rate of 3%.\u003c/p\u003e\u003cdiv id=\"Sec8\" class=\"Section2\"\u003e\u003ch2\u003eSensitivity analysis\u003c/h2\u003e\u003cp\u003eUncertainty in model parameters was explored using probabilistic sensitivity analysis (PSA) with 1,000 Monte Carlo simulations. Input parameters were sampled from appropriate probability distributions: beta for probabilities and utilities, and gamma for costs. PSA results were presented as cost-effectiveness acceptability curves (CEACs) and cost-effectiveness planes. One-way sensitivity analyses were also performed to identify parameters exerting the greatest influence on model outcomes.\u003c/p\u003e\u003c/div\u003e\n\u003ch3\u003eBudget impact analysis\u003c/h3\u003e\n\u003cp\u003eA five-year budget impact analysis was undertaken from the payer\u0026rsquo;s perspective to estimate the incremental cost of expanding trastuzumab access to patients with node-negative tumors\u0026thinsp;\u0026gt;\u0026thinsp;2 cm and ER/PR-negative status. The number of eligible patients was estimated using national cancer registry data, HER2 positivity rates, and insurance enrollment figures. Annual costs included drug acquisition and laboratory testing. The incremental budget impact was calculated for both the current reimbursement policy and the proposed expanded-access scenario, and results were reported in Thai Baht (THB).\u003c/p\u003e\n\u003ch3\u003eBase-case cost-utility analysis\u003c/h3\u003e\n\u003cp\u003eIn the base-case scenario, adjuvant trastuzumab in combination with paclitaxel was associated with higher lifetime costs but yielded substantially greater health benefits compared with paclitaxel monotherapy. The mean lifetime cost per patient was THB 989,794 in the trastuzumab arm and THB 606,142 in the paclitaxel-only arm. Patients receiving trastuzumab achieved 12.69 quality-adjusted life years (QALYs) versus 8.10 QALYs for paclitaxel alone, corresponding to an incremental gain of 4.59 QALYs. This translated into an incremental cost-effectiveness ratio (ICER) of THB 83,520 per QALY gained, which is well below the Thai cost-effectiveness threshold of THB 160,000 per QALY. These results are summarized in Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e.\u003c/p\u003e\u003cp\u003e\u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab2\" border=\"1\"\u003e\u003ccaption language=\"En\"\u003e\u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e\u003cdiv class=\"CaptionContent\"\u003e\u003cp\u003eBase-case cost-utility results\u003c/p\u003e\u003c/div\u003e\u003c/caption\u003e\u003ccolgroup cols=\"4\"\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e\u003cthead\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\"\u003e\u003cp\u003eOutcome\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c2\"\u003e\u003cp\u003eTrastuzumab\u0026thinsp;+\u0026thinsp;Paclitaxel\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c3\"\u003e\u003cp\u003ePaclitaxel alone\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c4\"\u003e\u003cp\u003eIncremental difference\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eCost (THB)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e989,794\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e606,142\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e383,653\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eLife years (years)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e14.12\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e9.11\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e5.01\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eQuality-adjusted life years (QALYs)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e12.69\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e8.10\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e4.59\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eICER (THB per QALY gained)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e\u0026ndash;\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e\u0026ndash;\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e83,520\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/colgroup\u003e\u003ctfoot\u003e\u003ctr\u003e\u003ctd colspan=\"4\"\u003eNote: ICER\u0026thinsp;=\u0026thinsp;Incremental cost-effectiveness ratio; QALY\u0026thinsp;=\u0026thinsp;Quality-adjusted life year; THB\u0026thinsp;=\u0026thinsp;Thai Baht.\u003c/td\u003e\u003c/tr\u003e\u003c/tfoot\u003e\u003c/table\u003e\u003c/div\u003e\u003c/p\u003e\u003cp\u003eThe improved cost-effectiveness relative to previous Thai evaluations is primarily attributable to the introduction of biosimilar trastuzumab via national pooled procurement, which has reduced the unit price by more than 60% compared with the originator product. This substantial price reduction has markedly lowered the incremental cost per patient, strengthening the economic justification for continued inclusion of trastuzumab in the national reimbursement framework.\u003c/p\u003e\u003cp\u003eIncorporating the costs of HER2 and hormone receptor testing had only a modest impact on the ICER. Although these diagnostics are essential for ensuring appropriate patient selection, their contribution to total treatment cost was relatively small in the context of biosimilar pricing. Similarly, inclusion of the costs associated with cardiac adverse event management, based on an estimated 2% incidence of congestive heart failure (CHF) among trastuzumab-treated patients, had minimal influence on the ICER. This reflects both the low frequency and the typically reversible nature of such events when appropriately monitored and managed.\u003c/p\u003e\u003cdiv id=\"Sec11\" class=\"Section2\"\u003e\u003ch2\u003eSensitivity analysis\u003c/h2\u003e\u003cp\u003eProbabilistic sensitivity analysis (PSA) confirmed the robustness of the base-case findings, with more than 90% of simulations indicating cost-effectiveness at a willingness-to-pay (WTP) threshold of THB 100,000 per QALY, and the vast majority falling below the official Thai threshold of THB 160,000 per QALY. The incremental cost-effectiveness plane (Fig.\u0026nbsp;2) presents the scatter plot of 1,000 Monte Carlo simulations for trastuzumab versus paclitaxel alone. Most simulated ICER points lie below the Thai cost-effectiveness threshold of THB 160,000 per QALY, indicating a high probability of cost-effectiveness. The cost-effectiveness acceptability curve (Fig.\u0026nbsp;3) illustrates the probability of trastuzumab being cost-effective across a range of WTP thresholds; at THB 160,000 per QALY, the probability exceeds 95%, reinforcing the favorable economic profile of the intervention. The results of the one-way sensitivity analysis are depicted in the tornado diagram (Fig.\u0026nbsp;4), which ranks model parameters according to their impact on the ICER. The most influential parameters were the transition probabilities from the disease-free to metastatic state in later years for both the trastuzumab and paclitaxel arms, followed by the annual cost of trastuzumab. Other parameters with notable influence included the cost of CT scans, the utility weight assigned to metastatic breast cancer, and the costs of outpatient visits and capecitabine. In contrast, variation in the probability of death from the disease-free state in the trastuzumab arm exerted minimal influence on the ICER. Across all plausible parameter ranges, trastuzumab remained cost-effective, underscoring the stability of the model\u0026rsquo;s conclusions.\u003c/p\u003e\u003c/div\u003e\u003cdiv id=\"Sec12\" class=\"Section2\"\u003e\u003ch2\u003eBudget impact analysis\u003c/h2\u003e\u003cp\u003eUnder current reimbursement criteria restricted to node-positive disease, the annual number of eligible patients was estimated at 4,342 (3,277 prevalent and 1,065 incident cases) (Table\u0026nbsp;\u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e3\u003c/span\u003e). Expanding coverage to include node-negative patients with tumors\u0026thinsp;\u0026gt;\u0026thinsp;2 cm and ER/PR-negative status would increase the eligible population by approximately 963 patients annually (727 prevalent and 236 incident cases). In the first year following policy expansion, the total projected cost of trastuzumab treatment and associated laboratory testing was THB 914.8\u0026nbsp;million, comprising THB 862.6\u0026nbsp;million for drug acquisition and THB 52.2\u0026nbsp;million for diagnostics. In subsequent years, when only incident cases would require treatment, the annual total cost was projected at THB 297.3\u0026nbsp;million (THB 280.4\u0026nbsp;million for drugs and THB 17.0\u0026nbsp;million for diagnostics). Compared with the current policy, the expanded-access scenario would result in incremental costs of THB 53.9\u0026nbsp;million in Year 1 and THB 24.5\u0026nbsp;million annually thereafter (Table\u0026nbsp;\u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e3\u003c/span\u003e, Fig.\u0026nbsp;5).\u003c/p\u003e\u003cp\u003e\u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab3\" border=\"1\"\u003e\u003ccaption language=\"En\"\u003e\u003cdiv class=\"CaptionNumber\"\u003eTable 3\u003c/div\u003e\u003cdiv class=\"CaptionContent\"\u003e\u003cp\u003eFive-Year Budget Impact of Adjuvant Trastuzumab Under Current and Expanded-Access Scenarios (Payer Perspective)\u003c/p\u003e\u003c/div\u003e\u003c/caption\u003e\u003ccolgroup cols=\"6\"\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e\u003cthead\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\"\u003e\u003cp\u003eYear\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c2\"\u003e\u003cp\u003eEligible Patients (n)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c3\"\u003e\u003cp\u003eDrug Acquisition Cost (THB million)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c4\"\u003e\u003cp\u003eDiagnostic Testing Cost (THB million)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c5\"\u003e\u003cp\u003eTotal Annual Cost (THB million)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c6\"\u003e\u003cp\u003eIncremental Cost vs. Current Policy (THB million)\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colspan=\"6\" nameend=\"c6\" namest=\"c1\"\u003e\u003cp\u003eCurrent Reimbursement Policy (Node-positive only)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e1\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e4,342\u003c/p\u003e\u003cp\u003e(3,277 prevalent, 1,065 incident)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e808.7\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e49.6\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e858.3\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e\u0026ndash;\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e2\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e1,065 (incident only)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e256.9\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e15.9\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e272.8\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e\u0026ndash;\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e3\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e1,065\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e256.9\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e15.9\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e272.8\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e\u0026ndash;\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e4\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e1,065\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e256.9\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e15.9\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e272.8\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e\u0026ndash;\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e5\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e1,065\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e256.9\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e15.9\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e272.8\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e\u0026ndash;\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colspan=\"6\" nameend=\"c6\" namest=\"c1\"\u003e\u003cp\u003eExpanded Access (+\u0026thinsp;Node-negative\u0026thinsp;\u0026gt;\u0026thinsp;2 cm, ER/PR\u0026ndash;negative)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e1\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e5,305\u003c/p\u003e\u003cp\u003e(4,004 prevalent, 1,301 incident)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e862.6\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e52.2\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e914.8\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e+\u0026thinsp;53.9\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e2\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e1,301 (incident only)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e280.4\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e17.0\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e297.3\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e+\u0026thinsp;24.5\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e3\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e1,301\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e280.4\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e17.0\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e297.3\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e+\u0026thinsp;24.5\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e4\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e1,301\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e280.4\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e17.0\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e297.3\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e+\u0026thinsp;24.5\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e5\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e1,301\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e280.4\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e17.0\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e297.3\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e+\u0026thinsp;24.5\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/colgroup\u003e\u003ctfoot\u003e\u003ctr\u003e\u003ctd colspan=\"6\"\u003eNotes: All costs are in 2024 Thai Baht (THB), adjusted using the medical consumer price index. Diagnostic costs include HER2 and hormone receptor testing, echocardiography, and cardiac monitoring. The expanded-access scenario assumes full uptake among eligible node-negative patients with tumors\u0026thinsp;\u0026gt;\u0026thinsp;2 cm and ER/PR-negative status.\u003c/td\u003e\u003c/tr\u003e\u003c/tfoot\u003e\u003c/table\u003e\u003c/div\u003e\u003c/p\u003e\u003cp\u003eAlthough the additional expenditure is substantial in absolute terms, the reduced per-patient cost facilitated by biosimilar procurement (THB 215,448 on average compared with THB 475,921 in earlier analyses) significantly mitigates the fiscal impact. When considered alongside the favorable cost-effectiveness profile and potential clinical benefit in high-risk node-negative patients, these findings support the financial feasibility of expanding trastuzumab access within the Thai Universal Coverage Scheme.\u003c/p\u003e\u003c/div\u003e"},{"header":"Discussion","content":"\u003cp\u003eThis study evaluated the cost-effectiveness and budget impact of adjuvant trastuzumab combined with paclitaxel versus paclitaxel monotherapy for early-stage HER2-positive breast cancer in Thailand. The updated analysis addressed key gaps in previous evaluations by incorporating the costs of HER2 and hormone receptor testing, as well as the clinical and economic consequences of trastuzumab-induced cardiac toxicity. The use of current biosimilar pricing ensures that the results reflect real-world procurement conditions under Thailand\u0026rsquo;s national healthcare system.\u003c/p\u003e\u003cp\u003eThe results confirmed that trastuzumab remains highly cost-effective, with an incremental cost-effectiveness ratio (ICER) of 83,520 Thai Baht (THB) per quality-adjusted life year (QALY) gained, well below the national threshold of 160,000 THB per QALY (ref). Compared with earlier analyses based on originator pricing, this ICER represents a marked improvement, primarily due to a 68% reduction in unit cost following the adoption of biosimilar trastuzumab through centralized procurement. Cardiac adverse events, which occur in approximately 2% of patients receiving trastuzumab [21, 22], and the inclusion of diagnostic testing costs had only a minimal effect on overall QALYs and total costs, indicating that these factors do not undermine the intervention\u0026rsquo;s economic value. This enhances the external validity of the model by aligning it more closely with routine clinical practice.\u003c/p\u003e\u003cp\u003eThe expanded coverage scenario, which includes node-negative patients with tumors larger than 2 centimeters and who are ER/PR-negative, also demonstrated cost-effectiveness. The ICER for this subgroup remained below the national threshold, and probabilistic sensitivity analysis indicated a greater than 90% probability of cost-effectiveness across plausible parameter ranges. This finding is notable because such patients were previously excluded from reimbursement on fiscal grounds, despite having a higher risk of recurrence compared with other node-negative groups.\u003c/p\u003e\u003cp\u003eFrom a budgetary perspective, extending coverage is projected to increase annual public expenditure by approximately 53.92\u0026nbsp;million THB. However, biosimilar pricing has reduced the average treatment cost per patient to 215,448 THB, compared with 475,921 THB in earlier studies [8]. The total five-year budget impact for both current and expanded patient groups is estimated at 297.34\u0026nbsp;million THB annually, a level that appears manageable within the Thai Universal Health Coverage (UHC) framework. These results suggest that expanding reimbursement would deliver substantial health gains at an affordable budgetary cost, representing an efficient allocation of limited healthcare resources.\u003c/p\u003e\u003cp\u003eMaximising the value of expanded coverage requires clearly defined eligibility criteria incorporating HER2 status, tumour size thresholds, and hormone receptor status. Establishing these parameters will facilitate appropriate patient selection, ensure equitable access, and optimise resource allocation. Furthermore, continued price negotiations for biosimilar trastuzumab and the introduction of financial support mechanisms for diagnostic testing could sustain long-term affordability and minimise financial barriers to treatment.\u003c/p\u003e"},{"header":"Conclusion","content":"\u003cp\u003eThis updated economic evaluation provides robust and policy-relevant evidence that adjuvant biosimilar trastuzumab, when administered in combination with paclitaxel, is a cost-effective intervention for early-stage HER2-positive breast cancer in Thailand. By incorporating diagnostic testing costs and the clinical and economic implications of trastuzumab-associated cardiac toxicity, the analysis offers a more comprehensive and realistic assessment of value under routine care conditions.\u003c/p\u003e\u003cp\u003eThe findings demonstrate that expanding reimbursement to include high-risk node-negative patients with tumours larger than 2 cm and ER/PR-negative status meets the national cost-effectiveness threshold, with only a modest projected increase in public expenditure. This expansion is further facilitated by a substantial reduction in per-patient treatment costs following biosimilar procurement.\u003c/p\u003e\u003cp\u003e To translate this evidence into practice, policymakers should update national coverage guidelines to reflect current cost-effectiveness data and clearly define eligibility criteria based on HER2 status, tumour size, and hormone receptor profile. Continued price negotiations for biosimilar trastuzumab, coupled with targeted financial support for diagnostic testing, could strengthen affordability and reduce barriers to equitable access.\u003c/p\u003e\u003cp\u003eOverall, this study supports evidence-informed updates to Thailand\u0026rsquo;s Universal Health Coverage policy. Expanding trastuzumab access in this manner would optimise the allocation of limited healthcare resources while advancing the national objective of delivering equitable, high-quality cancer care.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eEthics approval and consent to participate\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNot applicable. This study used secondary data from published sources and national databases; no human participants were directly involved.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent for publication\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNot applicable.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAvailability of data and materials\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe datasets generated and/or analysed during the current study are available from the corresponding author on reasonable request.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCompeting interests\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors declare that they have no competing interests.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis research received no specific grant from any funding agency in the public, commercial, or not-for-profit sectors.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthors\u0026rsquo; contributions\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eSL conceived and designed the study, developed the economic model, performed the analysis, and drafted the manuscript. RK contributed to the study design, provided clinical input for model parameters, validated results, and critically revised the manuscript. Both authors read and approved the final manuscript.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eFerlay J, Ervik M, Lam F, Colombet M, Mery L, Pi\u0026ntilde;eros M, Znaor A, Soerjomataram I, Bray F: \u003cstrong\u003eGlobal cancer observatory: cancer today\u003c/strong\u003e. \u003cem\u003eLyon: International agency for research on cancer \u003c/em\u003e2020, 20182020.\u003c/li\u003e\n\u003cli\u003eGinsburg O, Yip CH, Brooks A, Cabanes A, Caleffi M, Dunstan Yataco JA, Gyawali B, McCormack V, McLaughlin de Anderson M, Mehrotra R: \u003cstrong\u003eBreast cancer early detection: A phased approach to implementation\u003c/strong\u003e. \u003cem\u003eCancer \u003c/em\u003e2020, 126:2379-2393.\u003c/li\u003e\n\u003cli\u003eAli-Thompson S, Daly GR, Dowling GP, Kilkenny C, Cox L, McGrath J, AlRawashdeh MeM, Naidoo S, Power C, Hill AD: \u003cstrong\u003eA bibliometric analysis of HER\u003c/strong\u003e2-\u003cstrong\u003epositive breast cancer: \u003c/strong\u003e1987\u0026ndash;2024. \u003cem\u003eFrontiers in Oncology \u003c/em\u003e2024, 14:1355353.\u003c/li\u003e\n\u003cli\u003eCronin KA, Harlan LC, Dodd KW, Abrams JS, Ballard-Barbash R: \u003cstrong\u003ePopulation-based estimate of the prevalence of HER-\u003c/strong\u003e2\u003cstrong\u003e positive breast cancer tumors for early stage patients in the US\u003c/strong\u003e. \u003cem\u003eCancer investigation \u003c/em\u003e2010, 28(9):963-968.\u003c/li\u003e\n\u003cli\u003eMueller V, Bartsch R, Lin NU, Montemurro F, Pegram MD, Tolaney SM: \u003cstrong\u003eEpidemiology, clinical outcomes, and unmet needs of patients with human epidermal growth factor receptor \u003c/strong\u003e2-\u003cstrong\u003epositive breast cancer and brain metastases: A systematic literature review\u003c/strong\u003e. \u003cem\u003eCancer treatment reviews \u003c/em\u003e2023, 115:102527.\u003c/li\u003e\n\u003cli\u003eHassing CM, Nielsen DL, Knoop AS, Tvedskov THF, Kroman N, Laenkholm A-V, Juhl CB, Kuemler I: \u003cstrong\u003eAdjuvant treatment with trastuzumab of patients with HER\u003c/strong\u003e2-\u003cstrong\u003epositive, T\u003c/strong\u003e1\u003cstrong\u003ea-bN\u003c/strong\u003e0\u003cstrong\u003eM\u003c/strong\u003e0\u003cstrong\u003e breast tumors: A systematic review and meta-analysis\u003c/strong\u003e. \u003cem\u003eCritical Reviews in Oncology/Hematology \u003c/em\u003e2023, 184:103952.\u003c/li\u003e\n\u003cli\u003eEarl HM, Hiller L, Dunn JA, Patel M, Conte P, D\u0026rsquo;Amico R, Guarneri V, Joensuu H, Huttunen T, Hatzidaki D: \u003cstrong\u003eReduced duration adjuvant trastuzumab in the treatment of patients with HER\u003c/strong\u003e2-\u003cstrong\u003epositive breast cancer: a meta-analysis of randomised controlled non-inferiority trials including IPD data\u003c/strong\u003e. \u003cem\u003eBMJ oncology \u003c/em\u003e2025, 4(1):e000810.\u003c/li\u003e\n\u003cli\u003eKongsakon R, Lochid-Amnuay S, Kapol N, Pattanaprateep O: \u003cstrong\u003eFrom research to policy implementation: trastuzumab in early-stage breast cancer treatment in Thailand\u003c/strong\u003e. \u003cem\u003eValue in Health Regional Issues \u003c/em\u003e2019, 18:47-53.\u003c/li\u003e\n\u003cli\u003eJacobs TW, Gown AM, Yaziji H, Barnes MJ, Schnitt SJ: \u003cstrong\u003eComparison of fluorescence in situ hybridization and immunohistochemistry for the evaluation of HER-\u003c/strong\u003e2/\u003cstrong\u003eneu in breast cancer\u003c/strong\u003e. \u003cem\u003eJournal of clinical oncology \u003c/em\u003e1999, 17(7):1974-1974.\u003c/li\u003e\n\u003cli\u003eRoman E, Cardoen B, Decloedt J, Roodhooft F: \u003cstrong\u003eVariability in hospital treatment costs: a time-driven activity-based costing approach for early-stage invasive breast cancer patients\u003c/strong\u003e. \u003cem\u003eBMJ open \u003c/em\u003e2020, 10(7):e035389.\u003c/li\u003e\n\u003cli\u003eSharaf B, Tamimi F, Al-Abdallat H, Khater S, Salama O, Zayed A, El Khatib O, Qaddoumi A, Horani M, Al-Masri Y: \u003cstrong\u003eDual Anti-HER\u003c/strong\u003e2\u003cstrong\u003e Therapy vs trastuzumab alone with neoadjuvant anthracycline and taxane in HER\u003c/strong\u003e2-\u003cstrong\u003ePositive early-stage breast cancer: real-world insights\u003c/strong\u003e. \u003cem\u003eBiologics: Targets and Therapy \u003c/em\u003e2025:59-71.\u003c/li\u003e\n\u003cli\u003eHealth Intervention and Technology Assessment Program (HITAP): \u003cstrong\u003eGuideline for Health Technology Assessment in Thailand, Revised Edition \u003c/strong\u003e2021. 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Nonthaburi: Health Intervention and Technology Assessment Program (HITAP); 2018.\u003c/li\u003e\n\u003cli\u003eHornberger J, Kerrigan M, Foutel V: \u003cstrong\u003eCost-effectiveness of trastuzumab (Herceptin) for treatment of metastatic breast cancer\u003c/strong\u003e. \u003cem\u003eAnn Oncol \u003c/em\u003e2002, 13(Suppl 5):52.\u003c/li\u003e\n\u003cli\u003eSkedgel C, Rayson D, Younis T: \u003cstrong\u003eThe cost‐utility of sequential adjuvant trastuzumab in women with Her\u003c/strong\u003e2/\u003cstrong\u003eNeu‐positive breast cancer: An analysis based on updated results from the HERA Trial\u003c/strong\u003e. \u003cem\u003eValue in Health \u003c/em\u003e2009, 12(5):641-648.\u003c/li\u003e\n\u003cli\u003eHuszno J, Leś D, Sarzyczny-Słota D, Nowara E: \u003cstrong\u003eCardiac side effects of trastuzumab in breast cancer patients\u0026ndash;single centere experiences\u003c/strong\u003e. \u003cem\u003eContemporary Oncology/Wsp\u0026oacute;łczesna Onkologia \u003c/em\u003e2013, 17(2):190-195.\u003c/li\u003e\n\u003cli\u003ePiccart-Gebhart MJ, Procter M, Leyland-Jones B, Goldhirsch A, Untch M, Smith I, Gianni L, Baselga J, Bell R, Jackisch C: \u003cstrong\u003eTrastuzumab after adjuvant chemotherapy in HER\u003c/strong\u003e2-\u003cstrong\u003epositive breast cancer\u003c/strong\u003e. \u003cem\u003eNew England Journal of Medicine \u003c/em\u003e2005, 353(16):1659-1672.\u003c/li\u003e\n\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":true,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"bmc-health-services-research","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"bhsr","sideBox":"Learn more about [BMC Health Services Research](http://bmchealthservres.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/BHSR/default.aspx","title":"BMC Health Services Research","twitterHandle":"BMC_series","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"Trastuzumab, Biosimilar, Cost-utility analysis, Cardiac toxicity, HER2-positive breast cancer, Budget impact, Expanded access, Thailand","lastPublishedDoi":"10.21203/rs.3.rs-7344634/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-7344634/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eBackground\u003c/h2\u003e\u003cp\u003eTrastuzumab is an established adjuvant therapy for early-stage HER2-positive breast cancer. Previous studies in Thailand demonstrated its cost-effectiveness, but earlier evaluations did not account for trastuzumab-related cardiac adverse events, costs of HER2 and hormone receptor testing, or the budgetary implications of expanding treatment eligibility. This updated economic evaluation incorporates biosimilar drug pricing, the clinical and economic burden of cardiotoxicity, and diagnostic testing costs, and assesses the impact of expanding access to patients with node-negative tumors larger than 2 cm and ER/PR-negative status.\u003c/p\u003e\u003ch2\u003eMethods\u003c/h2\u003e\u003cp\u003eA cost-utility analysis using a Markov model was conducted from a societal perspective over a lifetime horizon, comparing trastuzumab plus paclitaxel with paclitaxel monotherapy. Updated costs, transition probabilities for disease progression and cardiac events, and utility weights were applied. Direct medical, direct non-medical, and indirect costs were included, adjusted to 2024 Thai Baht (THB), with costs and quality-adjusted life years (QALYs) discounted at 3% annually. A budget impact analysis estimated the incremental cost of expanding reimbursement criteria to the additional eligible subgroup.\u003c/p\u003e\u003ch2\u003eResults\u003c/h2\u003e\u003cp\u003eTrastuzumab plus paclitaxel resulted in higher lifetime costs (THB 989,794 vs. THB 606,142) and greater health benefits (12.69 vs. 8.10 QALYs) than paclitaxel alone, yielding an incremental cost-effectiveness ratio (ICER) of THB 83,520 per QALY gained, well below Thailand\u0026rsquo;s cost-effectiveness threshold of THB 160,000 per QALY. Incorporating cardiac toxicity and diagnostic testing costs had minimal impact on ICER, reflecting the low incidence and reversibility of cardiotoxicity. The projected annual budget impact of expanding coverage to the additional patient subgroup was THB 53.9\u0026nbsp;million, representing a modest increase relative to expected clinical benefits.\u003c/p\u003e\u003ch2\u003eConclusions\u003c/h2\u003e\u003cp\u003eBiosimilar trastuzumab remains a cost-effective adjuvant therapy for early-stage HER2-positive breast cancer in Thailand, even after accounting for cardiac adverse events and diagnostic testing costs. The findings support expanding reimbursement to high-risk node-negative patients with ER/PR-negative tumors larger than 2 cm, consistent with value-based policy expansion and efficient use of healthcare resources.\u003c/p\u003e","manuscriptTitle":"Cost-Utility and Budget Impact Analysis of Biosimilar Trastuzumab for Early-Stage HER2- Positive Breast Cancer in Thailand: An Updated Evaluation Supporting Expanded Access","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-08-13 05:54:36","doi":"10.21203/rs.3.rs-7344634/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Revision requested","date":"2025-12-15T20:27:23+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2025-12-10T08:46:05+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"8935590702165552741998255562985358590","date":"2025-12-10T06:56:53+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2025-08-25T18:36:30+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"203347126215385267617512508219882543964","date":"2025-08-20T12:38:39+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2025-08-20T00:43:09+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2025-08-13T00:41:47+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2025-08-13T00:41:36+00:00","index":"","fulltext":""},{"type":"submitted","content":"BMC Health Services Research","date":"2025-08-11T09:16:20+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"bmc-health-services-research","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"bhsr","sideBox":"Learn more about [BMC Health Services Research](http://bmchealthservres.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/BHSR/default.aspx","title":"BMC Health Services Research","twitterHandle":"BMC_series","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"14af85eb-b66c-45ec-8ba3-f981ae8c600f","owner":[],"postedDate":"August 13th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"published-in-journal","subjectAreas":[],"tags":[],"updatedAt":"2026-02-02T16:02:42+00:00","versionOfRecord":{"articleIdentity":"rs-7344634","link":"https://doi.org/10.1186/s12913-026-14094-0","journal":{"identity":"bmc-health-services-research","isVorOnly":false,"title":"BMC Health Services Research"},"publishedOn":"2026-01-29 15:59:33","publishedOnDateReadable":"January 29th, 2026"},"versionCreatedAt":"2025-08-13 05:54:36","video":"","vorDoi":"10.1186/s12913-026-14094-0","vorDoiUrl":"https://doi.org/10.1186/s12913-026-14094-0","workflowStages":[]},"version":"v1","identity":"rs-7344634","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-7344634","identity":"rs-7344634","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}