Cost-utility analysis of sacituzumab govitecan versus chemotherapy for the treatment of metastatic triple-negative breast cancer in Singapore.

OBJECTIVE: To assess the cost-effectiveness of sacituzumab govitecan for treating relapsed or refractory metastatic triple-negative breast cancer (TNBC) in Singapore. METHODS: A three-state partitioned survival model was developed to evaluate the cost-effectiveness of sacituzumab govitecan from a healthcare system perspective over 5 years. Clinical inputs were obtained from the ASCENT trial. Health state utilities were retrieved from the literature and direct costs were sourced from public healthcare institutions in Singapore. Sensitivity and scenario analyses were conducted to explore the impact of uncertainties and assumptions on cost-effectiveness results. RESULTS: Compared with single-agent chemotherapy, sacituzumab govitecan was associated with a base-case incremental cost-effectiveness ratio (ICER) of S$328,000 (US$237,816) per quality-adjusted life year (QALY) gained. One-way sensitivity analyses showed that the ICER was most sensitive to the cost of sacituzumab govitecan and progression-free utility values. Regardless of variation in these parameters, the ICER remained high, and a substantial price reduction was required to reduce the ICER. CONCLUSION: At its current price, sacituzumab govitecan does not represent a cost-effective treatment for relapsed or refractory metastatic TNBC in Singapore. Our findings will be useful to inform funding decisions alongside other factors including clinical effectiveness, safety, and budget impact considerations.

Cost-effectiveness of transcatheter aortic valve implantation in patients with severe symptomatic aortic stenosis of intermediate surgical risk in Singapore.

OBJECTIVE: The objective was to assess the cost-effectiveness of transcatheter aortic valve implantation (TAVI) in patients with severe aortic stenosis with intermediate surgical risk in Singapore. METHODS: A de novo Markov model with three health states - stroke with long-term sequelae, no stroke, and death - was developed and simulated using Monte Carlo simulations with 10,000 iterations over a five-year time horizon from the Singapore healthcare system perspective. A 3% annual discount rate for costs and outcomes and monthly cycle lengths were used. By applying the longest available published clinical evidence, simulated patients received either TAVI or surgical aortic valve replacement (SAVR) and were at risk of adverse events (AEs) such as moderate-to-severe paravalvular aortic regurgitation (PAR). RESULTS: When five-year PARTNER 2A data was applied, base-case analyses showed that the incremental cost-effectiveness ratio (ICER) for TAVI compared to SAVR was US$315,760 per quality-adjusted life year (QALY) gained. The high ICER was due to high incremental implantation and procedure costs of TAVI compared to SAVR, and marginal improvement of 0.10 QALYs as simulated mortality of TAVI exceeded SAVR at 3.75 years post-implantation. One-way sensitivity analysis showed that the ICERs were most sensitive to cost of PAR, utility values of SAVR patients, and cost of TAVI and SAVR implants and procedures. When disutilities for AEs were additionally applied, the ICER decreased to US$300,070 per QALY gained. TAVI was dominated by SAVR when the time horizon increased to 20 years. Clinical outcomes projected from one-year PARTNER S3i data further reduced the ICER to US$86,337 per QALY gained for TAVI, assuming early all-cause mortality benefits from TAVI continued to persist. This assumption was undermined when longer term data showed that TAVI's early mortality benefits diminished at five years. LIMITATIONS AND CONCLUSION: TAVI is unlikely to be cost-effective in intermediate surgical-risk patients compared to SAVR in Singapore.

Assessing the cost-effectiveness of mepolizumab as add-on therapy to standard of care for severe eosinophilic asthma in Singapore.

OBJECTIVE: To evaluate the cost-effectiveness of mepolizumab added to standard of care (SOC) compared with SOC alone among patients with severe uncontrolled eosinophilic asthma in the Singapore setting. METHODS: A Markov model with three health states (asthma on mepolizumab and SOC, asthma on SOC alone, and death) was developed from a healthcare system perspective over a lifetime horizon. During each 4-week cycle, patients in the non-death health states could experience asthma exacerbations requiring oral corticosteroid burst, emergency department visit, or hospitalization. Asthma-related mortality following an exacerbation or all-cause mortality could also occur at each cycle. The model was populated using local costs while utilities were derived from international literature. Transition probabilities were obtained from a mixture of Singapore-specific and internationally published data. RESULTS: The base-case analysis comparing mepolizumab plus SOC with SOC alone resulted in an incremental cost-effectiveness ratio (ICER) of SGD335 486 (USD238 195) per quality-adjusted life-year (QALY) gained. Sensitivity analysis demonstrated that the ICER was most sensitive to the price of mepolizumab, followed by the proportion of exacerbations which required hospital intensive care. Despite restricting mepolizumab use to patients with a higher baseline exacerbation rate (3 in the past year) in a scenario analysis, the ICER remained high at SGD238 876 (USD 169 602) per QALY gained. CONCLUSION: At its current price, mepolizumab is not considered a cost-effective use of healthcare resources in Singapore. Substantial price reductions for mepolizumab are required to improve its cost-effectiveness to an acceptable range. These results will be useful to inform national funding decisions.

Cost-effectiveness of daratumumab in combination with lenalidomide and dexamethasone for relapsed and/or refractory multiple myeloma.

OBJECTIVE: This study evaluates the cost-effectiveness of daratumumab (D) in combination with lenalidomide and dexamethasone (Rd) for treatment of relapsed and/or refractory multiple myeloma in patients who have received at least one prior therapy in Singapore. METHODS: A 3-state partitioned survival model was developed to evaluate the cost-effectiveness of lenalidomide and dexamethasone with or without daratumumab from a healthcare system perspective over 10 years. Clinical inputs were obtained from the POLLUX trial. Health state utilities were derived from the literature and direct medical costs obtained from public healthcare institutions. Sensitivity and scenario analyses were conducted to explore uncertainties. RESULTS: DRd was associated with a high base-case incremental cost-effectiveness ratio (ICER) of US$576,247 per quality-adjusted life year (QALY) gained, compared with Rd. According to one-way sensitivity analysis, ICER was most heavily influenced by time horizon, discount rate for outcomes, progression-free utility and cost of daratumumab. Regardless of the variation, DRd remained not cost-effective. Even when the cost of both daratumumab and lenalidomide dropped by 20% and 80%, the ICERs remained high at US$470,400 and US$152,860 per QALY gained. CONCLUSIONS: At current prices, the addition of daratumumab to lenalidomide and dexamethasone does not represent cost-effective use of healthcare resources in Singapore.

Cost-effectiveness of MRI targeted biopsy strategies for diagnosing prostate cancer in Singapore.

BACKGROUND: To evaluate the cost-effectiveness of six diagnostic strategies involving magnetic resonance imaging (MRI) targeted biopsy for diagnosing prostate cancer in initial and repeat biopsy settings from the Singapore healthcare system perspective. METHODS: A combined decision tree and Markov model was developed. The starting model population was men with mean age of 65 years referred for a first prostate biopsy due to clinical suspicion of prostate cancer. The six diagnostic strategies were selected for their relevance to local clinical practice. They comprised MRI targeted biopsy following a positive pre-biopsy multiparametric MRI (mpMRI) [Prostate Imaging - Reporting and Data System (PI-RADS) score ≥ 3], systematic biopsy, or saturation biopsy employed in different testing combinations and sequences. Deterministic base case analyses with sensitivity analyses were performed using costs from the healthcare system perspective and quality-adjusted life years (QALY) gained as the outcome measure to yield incremental cost-effectiveness ratios (ICERs). RESULTS: Deterministic base case analyses showed that Strategy 1 (MRI targeted biopsy alone), Strategy 2 (MRI targeted biopsy ➔ systematic biopsy), and Strategy 4 (MRI targeted biopsy ➔ systematic biopsy ➔ saturation biopsy) were cost-effective options at a willingness-to-pay (WTP) threshold of US$20,000, with ICERs ranging from US$18,975 to US$19,458. Strategies involving MRI targeted biopsy in the repeat biopsy setting were dominated. Sensitivity analyses found the ICERs were affected mostly by changes to the annual discounting rate and prevalence of prostate cancer in men referred for first biopsy, ranging between US$15,755 to US$23,022. Probabilistic sensitivity analyses confirmed Strategy 1 to be the least costly, and Strategies 2 and 4 being the preferred strategies when WTP thresholds were US$20,000 and US$30,000, respectively. LIMITATIONS AND CONCLUSIONS: This study found MRI targeted biopsy to be cost-effective in diagnosing prostate cancer in the biopsy-naïve setting in Singapore.

A review of implementation frameworks to operationalize health technology assessment recommendations for medical technologies in the Singapore setting.

BACKGROUND: Methodologies of health technology assessment (HTA) for medical technologies are well established; yet, operational frameworks that enable appropriate uptake of HTA recommendations into routine clinical practice are lacking. This review aims to identify the key themes needed to guide the planning and implementation of HTA subsidy decisions for medical technologies such as diagnostics, medical devices, and services and to monitor their impact on a complex multipayer healthcare system like Singapore. METHODS: A literature search of implementation frameworks was conducted up to 20 December 2020 and was documented in a flow diagram. A thematic analysis of the evidence base was performed using the Braun and Clark approach to identify key themes, from which an implementation framework suitable for Singapore's healthcare system could be developed. RESULTS: The searches yielded forty-four articles for review, from which twenty themes were identified. The top ten themes constituted the key themes of implementation essential for local adaptation and were categorized into five domains: implementation strategy, organizational support, stakeholder engagement, information dissemination, and implementation outcomes and evaluation. These domains provide operational guidance to methodically identify gaps to facilitate sustainable implementation of HTA-informed medical technology subsidy decisions. CONCLUSION: A robust and adaptable implementation of HTA-informed subsidy decisions is crucial to optimize its intended impact of improving patient outcomes per dollar spent. The key themes of an implementation framework should capture the important aspects of organizational feasibility to ensure successful adoption in a complex multipayer healthcare system like Singapore.

Cost-effectiveness analysis of the nonavalent human papillomavirus vaccine for the prevention of cervical cancer in Singapore.

BACKGROUND: The nonavalent human papillomavirus (HPV) vaccine has been shown to extend protection against oncogenic HPV types 31/33/45/52/58 (HPV-OV) not covered by the bivalent and quadrivalent HPV vaccines. Besides its clinical benefit, evidence on the economic value of the nonavalent vaccine is required to inform local vaccination strategies and funding decisions. This study evaluated the cost-effectiveness of replacing the bivalent vaccine with the nonavalent vaccine in the national school-based HPV vaccination programme in Singapore. METHODS: An existing age-structured dynamic transmission model coupled with stochastic individual-based simulations was adapted to project the health and economic impact of vaccinating 13-year-old girls with two doses of the nonavalent or bivalent HPV vaccines in Singapore. Direct costs (in Singapore dollars, S$) were obtained from public healthcare institutions in Singapore, while health state utilities were sourced from the literature. Incremental cost-effectiveness ratios (ICERs) were estimated over a lifetime horizon, from a healthcare system perspective. Probabilistic sensitivity analysis was performed to obtain the ICERs and corresponding variations across variable uncertainty. Particularly, this study tested the scenarios of lifelong and 20-year vaccine-induced protection, assumed 96.0% and 22.3% cross-protection against HPV-OV by nonavalent and bivalent vaccines respectively, and fixed vaccine prices per dose at S$188 for nonavalent and S$61.50 for bivalent vaccines. RESULTS: Compared with the bivalent vaccine, the use of the nonavalent vaccine was associated with an ICER of S$61,629 per quality-adjusted life year gained in the base case. The result was robust across a range of plausible input values, and to assumptions regarding the duration of vaccine protection. CONCLUSION: Given the high ICER, the nonavalent vaccine is unlikely to represent a cost-effective option compared with the bivalent vaccine for school-based HPV vaccination of 13-year old female students in Singapore. Substantial price reductions would be required to justify its inclusion in the school-based programme in the future.

Cost-effectiveness of pertuzumab and trastuzumab biosimilar combination therapy as initial treatment for HER2-positive metastatic breast cancer in Singapore.

BACKGROUND: This study evaluates the cost-effectiveness of pertuzumab with trastuzumab biosimilar and docetaxel as initial treatment for HER2-positive metastatic breast cancer (MBC) in Singapore. METHODS: A partitioned survival model with three health states was developed to evaluate the cost-effectiveness of trastuzumab biosimilar and docetaxel with or without pertuzumab from a healthcare system perspective over a 15-year time horizon for patients with HER2-positive MBC. Key clinical inputs were derived from the CLEOPATRA trial. Health state utilities were derived from the literature and direct medical costs were obtained from local public healthcare institutions. RESULTS: The base-case resulted in an incremental cost-effectiveness ratio (ICER) of SGD366,658 (USD272,244) per quality-adjusted life-year (QALY) gained. One-way sensitivity analyses showed that the ICER was sensitive to utilities in the progression-free state, price of pertuzumab and time horizon. When the price for trastuzumab reference biologic (branded) was applied, the ICER was even higher (SGD426,996 [USD317,045]/QALY). CONCLUSION: Although trastuzumab biosimilar reduced the cost of the pertuzumab combination regimen, the ICER remained high and was not cost effective in Singapore's context. As pertuzumab contributed 80% of the overall combination treatment cost, price reductions for pertuzumab will be required to improve the cost-effectiveness of combination treatment to an acceptable level.

Cost-effectiveness of olaparib maintenance therapy when used with and without restriction by BRCA1/2 mutation status for platinum-sensitive relapsed ovarian cancer.

Objectives: To determine whether olaparib maintenance therapy, used with and without restriction by BRCA1/2 mutation status, is cost-effective at the population level for platinum-sensitive relapsed ovarian cancer in Singapore.Methods: A partitioned survival model compared three management strategies: 1) treat all patients with olaparib; 2) test for germline BRCA1/2 mutation, followed by targeted olaparib use in mutation carriers only; 3) observe all patients. Mature overall survival (OS) data from Study 19 and a 15-year time horizon were used and direct medical costs were applied. Sensitivity analyses were conducted to explore uncertainties.Results: Treating all patients with olaparib was the most costly and effective strategy, followed by targeted olaparib use, and observation of all patients. Base-case incremental cost-effectiveness ratios (ICERs) for all-olaparib and targeted use strategies were SGD133,394 (USD100,926) and SGD115,736 (USD87,566) per quality-adjusted life year (QALY) gained, respectively, compared to observation. ICERs were most sensitive to the cost of olaparib, time horizon and discount rate for outcomes. When these parameters were varied, ICERs remained above SGD92,000 (USD69,607)/QALY.Conclusions: At the current price, olaparib is not cost-effective when used with or without restriction by BRCA1/2 mutation status in Singapore, despite taking into account potential OS improvement over a long time horizon.

Cost-effectiveness of ribociclib as initial treatment for premenopausal women with advanced breast cancer in Singapore.

BACKGROUND: CDK4/6 inhibitors have shown promising results for treating advanced breast cancer (ABC) and are routinely used in Singapore. In view of their high costs, it is important to assess their relative value compared to existing standards of care in the local setting. AIMS: This study evaluates the cost-effectiveness of adding ribociclib to goserelin and a nonsteroidal aromatase inhibitor or tamoxifen as initial therapy for premenopausal women with hormone receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER2-) ABC in Singapore. METHODS: A partitioned survival model with four health states (progression-free on first-line treatment, progression-free on second-line treatment, progressed disease, and death) was developed from a healthcare system perspective over a 10-year time horizon. Key clinical inputs were derived from the MONALEESA-7 trial, and survival curves were extrapolated beyond the trial period. Health state utilities were derived from the literature and direct medical costs were obtained from local public healthcare institutions. A discount rate of 3% was applied to both costs and outcomes. One-way deterministic and probabilistic sensitivity analyses were conducted to explore uncertainties. RESULTS: The base-case analysis resulted in an incremental cost-effectiveness ratio (ICER) of SGD197, 667 per quality-adjusted life-year. Sensitivity analyses showed that the ICER was sensitive to the survival parametric distribution, ribociclib price, time horizon, and utility weights used. Even when these were varied, ICERs remained high and not cost-effective in the local context. CONCLUSION: At its current price, adding ribociclib to endocrine therapy is unlikely to be cost-effective in Singapore for HR+, HER2- ABC. Results from this study are useful to inform future funding decisions for CDK4/6 inhibitors alongside other factors including clinical effectiveness, safety, and budget impact considerations.

Cost-effectiveness analysis of osimertinib for first-line treatment of locally advanced or metastatic EGFR mutation positive non-small cell lung cancer in Singapore.

OBJECTIVE: Non-small cell lung cancer (NSCLC) accounts for 80-90% of all lung cancer cases and is usually associated with a poor prognosis. However, targeted therapy with first and second generation tyrosine kinase inhibitors (TKIs) has so far improved progression-free survival of epidermal growth factor receptor (EGFR) mutant NSCLC patients. Osimertinib, a third generation EGFR TKI has recently shown improved overall survival of 6.8 months in previously untreated EGFR mutant NSCLC patients. We assessed the cost-effectiveness of osimertinib versus standard EGFR TKIs (gefitinib or erlotinib) as first-line treatment for advanced or metastatic EGFR mutant NSCLC patients in Singapore. METHODS: A partitioned survival model with three health states (progression-free, progressive disease, and death) was developed from the Singapore healthcare payer perspective. Survival curves based on the overall trial population from the FLAURA trial were extrapolated beyond trial period over a 10-year time horizon to estimate the underlying progression-free survival and overall survival parametric distributions. Health state utilities were derived from the literature and direct costs were sourced from public healthcare institutions in Singapore. Deterministic and probabilistic sensitivity analyses were conducted to explore the impact of uncertainties and assumptions on cost-effectiveness results. RESULTS: Compared with first or second generation TKI, osimertinib had a base-case incremental cost-effectiveness ratio (ICER) of SG$418,839 (US$304,277) per quality-adjusted life year gained. One-way sensitivity analysis showed the ICER was most sensitive to time horizon and variations in progression-free utility values. Scenario analyses showed that a 50% reduction in the cost of osimertinib was still associated with a high ICER that was unlikely to be deemed cost effective. CONCLUSIONS: Osimertinib is not cost effective as a first-line treatment compared to standard EGFR TKIs in advanced EGFR mutant NSCLC patients in Singapore. The findings from our evaluation, alongside other considerations including the lack of survival benefit in the Asian subgroup of the FLAURA trial, will be useful to inform policy makers on funding decisions for NSCLC treatments in Singapore.

Cost utility analysis of tisagenlecleucel vs salvage chemotherapy in the treatment of relapsed/refractory diffuse large B-cell lymphoma from Singapore's healthcare system perspective.

BACKGROUND: Patients with relapsed or refractory diffuse large B-cell lymphoma (r/r DLBCL) have limited treatment options and poor prognoses. Tisagenlecleucel, a chimeric antigen receptor (CAR) T-cell therapy has shown early promise in improving survival outcomes, but at a high upfront cost. This study evaluated the cost-effectiveness of tisagenlecleucel versus salvage chemotherapy for treating patients with r/r DLBCL who have failed at least 2 lines of systemic therapies. METHODS: A hybrid decision tree and three-state partitioned survival model (progression-free (PF), progressive disease and death) was developed from the Singapore healthcare payer perspective. Survival curves from JULIET trial and CORAL-1 extension study were extrapolated beyond trial period over a 15-year time horizon to estimate the underlying progression-free survival and overall survival parametric distributions for both arms. Health state utilities were retrieved from the literature, and direct costs were sourced from public healthcare institutions in Singapore. One-way probabilistic sensitivity analyses and scenario analyses were conducted to explore the impact of uncertainties and assumptions on cost-effectiveness results. RESULTS: Compared with salvage chemotherapy, tisagenlecleucel was associated with a base-case incremental cost-effectiveness ratio (ICER) US$508,530 (S$686,516) per quality adjusted life year (QALY) gained and US$320,200 (S$432,269) per life year (LY) gained. One-way sensitivity analysis showed the ICER was most sensitive to time horizon, PF utility and cost of tisagenlecleucel. Scenario analyses confirmed that the ICERs remained high under favorable assumptions and substantial price reduction was required to reduce the ICER. CONCLUSIONS: Our analysis showed tisagenlecleucel use in r/r DLBCL patients who failed at least 2 prior lines of systemic therapies was associated with exceedingly high ICER, which is unlikely to represent good use of healthcare resources. Comparative clinical evidence from the ongoing trials might provide more insight into future evaluations.

Towards greater impact in health technology assessment: horizon scanning for new and emerging technologies in Singapore.

OBJECTIVES: To alert policy makers early about emerging health technologies that could significantly impact the healthcare system at the clinical, financial and organizational levels, the Agency for Care Effectiveness (ACE) in Singapore established a horizon scanning system (HSS) in 2019. This paper describes the development of the ACE HSS and showcases its application with cell and gene therapy products as the first example. METHODS: A literature review of existing HSS methods, including the processes of the EuroScan International Network and other overseas horizon scanning agencies, was done to inform the development of our horizon scanning framework. The framework was first applied to the new and emerging cell and gene therapies. RESULTS: Identification sources, filtration and prioritization criteria, and horizon scanning outputs for the HSS were developed in alignment to international best practices, with recommendations for technology uptake represented by a traffic light system. For the first horizon scanning exercise on cell and gene therapies, forty therapies passed the filtration step, of which eight were prioritized for further assessment. The few early reports developed were used to inform and prepare the healthcare system for their potential introduction, particularly in terms of the need to develop health and funding policies. CONCLUSIONS: Early assessment of prioritized topics has provided support for strategic efforts within the Ministry of Health. Given that ACE's horizon scanning program is still in its infancy, the framework will continue to evolve to ensure relevance to our stakeholders so that it remains fit for purpose for our healthcare system.

Cost-effectiveness analysis of atezolizumab in advanced triple-negative breast cancer.

BACKGROUND: The IMpassion130 trial demonstrated that adding atezolizumab to nanoparticle albumin-bound (nab)-paclitaxel improved the survival of patients with untreated, advanced, programmed death ligand 1 (PDL1)-positive triple-negative breast cancer (TNBC). In view of the high cost of immunotherapy, it is important to examine its value with respect to both benefits and costs. In this study, the cost-effectiveness of atezolizumab/nab-paclitaxel combination therapy relative to nab-paclitaxel monotherapy was evaluated for the first-line treatment of advanced, PDL1-positive TNBC, from a healthcare system perspective. METHODS: A three-state partitioned-survival model was developed to compare the clinical and economic outcomes of treatment with atezolizumab/nab-paclitaxel combination therapy with nab-paclitaxel monotherapy in patients with advanced TNBC. Clinical data were obtained from the IMpassion130 trial and extrapolated to 5 years. Health state utilities were retrieved from the literature, while direct costs (in Singapore dollars, S$) were sourced from public healthcare institutions in Singapore. The primary outcomes of the model were life years (LYs), quality-adjusted LYs (QALYs), costs and incremental cost-effectiveness ratios (ICERs). One-way and probabilistic sensitivity analyses and scenario analyses were conducted to explore the impact of specific assumptions and uncertainties. RESULTS: Adding atezolizumab to nab-paclitaxel resulted in an additional 0.361 QALYs (0.636 LYs) at an ICER of S$324,550 per QALY gained. The ICER remained high at S$67,092 per QALY even when atezolizumab was priced zero. One-way sensitivity analysis showed that the ICER was most sensitive to variations in the cost of atezolizumab and the time horizon. Scenario analyses confirmed that the ICERs remained high even under extremely favourable assumptions. CONCLUSIONS: Given the exceedingly high ICER, adding atezolizumab to nab-paclitaxel was unlikely to represent good value for money for the treatment of advanced PDL1-positive TNBC. Our findings will be useful in informing funding policy decisions alongside other considerations such as comparative effectiveness, unmet need and budget impact.

Cost-effectiveness analysis of pembrolizumab monotherapy versus chemotherapy for previously untreated advanced non-small cell lung cancer.

Objective: To assess the cost-effectiveness of pembrolizumab monotherapy compared with standard chemotherapy for the treatment of advanced non-small cell lung cancer (NSCLC) in previously untreated adults who have a high programmed death ligand 1 (PD-L1) tumor proportion score of 50% or greater in Singapore.Materials and methods: A partitioned-survival analysis model was developed from a healthcare system's perspective that extrapolated clinical and economic outcomes of first-line pembrolizumab (maximum treatment duration of 2 years) versus platinum doublet chemotherapy over a 10-year time horizon for patients with advanced NSCLC. The model consisted of three health states: alive with no progression, alive with progression, and dead. Key clinical inputs were based on Kaplan-Meier survival curves from the interim (median follow-up = 11.2 months) and updated analysis (median follow-up = 25.2 months) of the KEYNOTE-024 randomized controlled trial. Local cost data were applied. Utilities were derived from published international estimates. Both one-way and multivariate probabilistic sensitivity analyses (PSA) were conducted to identify key drivers of the results.Results: Using the results from the updated analysis of KEYNOTE-024, patients treated with pembrolizumab experienced more quality adjusted life-years (QALYs), but incurred higher costs compared to chemotherapy over a 10-year time horizon (pembrolizumab: 1.9983 QALYs, SGD215,761; chemotherapy: 1.1317 QALYs, SGD70,444). The base-case incremental cost-effectiveness ratio (ICER) was SGD167,692 per QALY gained. One-way sensitivity analysis showed the ICER was most sensitive to the cost of pembrolizumab, followed by the time horizon. Multivariate PSA indicated that pembrolizumab had 0% probability of being cost-effective at a hypothetical willingness-to-pay threshold of SGD100,000 per QALY gained.Conclusion: While pembrolizumab is superior to standard chemotherapy in improving overall survival and progression-free survival, results suggest that it is unlikely to be cost-effective at its current price in Singapore. Factors including clinical effectiveness, safety, and budget impact should also be considered when making national funding decisions.

Cost-effectiveness analysis of bilateral cochlear implants for children with severe-to-profound sensorineural hearing loss in both ears in Singapore.

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

Cost-Effectiveness Analysis of Sunitinib versus Interferon-Alfa for First-Line Treatment of Advanced and/or Metastatic Renal Cell Carcinoma in Singapore.

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

Health Technology Assessment and Its Use in Drug Policies: Singapore.

INTRODUCTION: Singapore has a robust health care system that is well known for delivering good health outcomes. In the public health care sector, subsidies and financial assistance are provided for drugs listed on the Standard Drug List and Medication Assistance Fund. Additional financing mechanisms are also available to provide further support for patients in need. With new technologies entering the market at high costs, health technology assessment (HTA) is playing an increasingly important role to inform their relative value and determine how best to allocate finite health care resources to ensure long-term sustainability of the health care system. ROLE OF HTA: National HTA efforts are currently focused on informing subsidy decision making and improving patient access to cost-effective drugs. The Agency for Care Effectiveness (ACE) was established in 2015 to support the Ministry of Health Drug Advisory Committee make evidence-based recommendations for the public funding of drugs. Standardized HTA methods and processes have been developed in line with international best practice to ensure that ACE's evaluations are conducted in a consistent and robust manner. Since ACE's establishment, subsidies are now provided earlier within a drug's life cycle, and value-based pricing has led to more cost-effective prices being negotiated with companies to improve affordability for patients and the public health care system. CONCLUSION: To achieve greater impact, Singapore needs to expand its HTA capacity beyond subsidy decision making and drive appropriate care in a sustainable manner for future generations.

Cost effectiveness analysis of afatinib versus pemetrexed-cisplatin for first-line treatment of locally advanced or metastatic EGFR mutation positive non-small-cell lung cancer from the Singapore healthcare payer's perspective.

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