Cost-effectiveness evaluation of the 10-valent pneumococcal non-typeable Haemophilus influenzae protein D conjugate vaccine for children in Taiwan.

BACKGROUND: Streptococcus pneumoniae (S. pneumoniae) and non-typeable Haemophilus influenzae (NTHi) are substantial contributors to morbidity and mortality of diseases including invasive pneumococcal diseases (IPDs), pneumonia and acute otitis media (AOM) worldwide. In Taiwan, 10-valent pneumococcal polysaccharide and NTHi protein D conjugate vaccine (PHiD-CV) and 13-valent pneumococcal conjugate vaccine (PCV13) are licensed in children against pneumococcal disease. In addition to S. pneumoniae, clinical trials suggest efficacy of PHiD-CV against NTHi AOM. This study aims at evaluating the cost-effectiveness of a 2 + 1 schedule of PHiD-CV vs. PCV13 2 + 1 in the universal mass vaccination program of infants in Taiwan. METHODS: A published Markov cohort model was adapted to simulate the epidemiological burden of IPD, pneumonia and AOM for a birth cohort in Taiwan over 10 years. The probability of entering a specific health state was based on the incidence rate of the diseases. Only direct medical costs were included, and costs and outcomes were discounted annually. Vaccine efficacy assumptions were based on published data and validated by a panel of independent experts. Clinical, epidemiological, and serotype distribution data were based on locally published data or the National Health Insurance Research Database. Price parity of vaccines was assumed. Published pneumococcal disease-related disutility weights were used due to lack of local data. Incremental cost-effectiveness ratio was calculated and benchmarked against the recommended threshold in Taiwan. Extensive one-way sensitivity analysis, alternative scenarios and probabilistic sensitivity analysis were performed to test the robustness of the results. RESULTS: PHiD-CV would potentially reduce the number of NTHi-related AOM cases substantially and prevent comparable IPD and pneumonia-related cases and deaths compared to PCV13. Over a 10-year horizon, PHiD-CV is estimated to dominate PCV13, saving 6.7 million New Taiwan Dollars (NTD) and saving 21 quality-adjusted life years. The result was robust over a wide range of sensitivity analyses. The dominance of PHiD-CV was demonstrated in 90.5% of the simulations. CONCLUSIONS: PHiD-CV 2 + 1 would provide comparable prevention of IPD, pneumonia cases and additional reduction of NTHi-AOM cases, and is considered dominant compared with PCV13 2 + 1 in Taiwan.

Cost Effectiveness of PD-L1-Based Test-and-Treat Strategy with Pembrolizumab as the First-Line Treatment for Metastatic NSCLC in Hong Kong.

BACKGROUND: Pembrolizumab, a monoclonal antibody against programmed death ligand 1 (PD-L1), is approved by several regulatory agencies for first-line treatment of metastatic non-small-cell lung cancer (NSCLC) with a PD-L1 tumor proportion score (TPS) ≥ 50% and no epidermal growth factor receptor (EGFR) or anaplastic lymphoma kinase genomic tumor aberrations. This study was conducted from the perspective of the Hospital Authority in Hong Kong and aimed to evaluate the cost effectiveness of a biomarker (PD-L1) test-and-treat strategy (BTS), in which patients with a TPS ≥ 50% received pembrolizumab and other patients received platinum doublet chemotherapy versus all patients receiving platinum doublet chemotherapy. METHODS: The model used a partitioned survival approach to estimate the incremental cost-effectiveness ratio (ICER) expressed as the cost per quality-adjusted life-year (QALY) gained. The clinical efficacy, utility and safety data were derived from the KN024 trial. Costs and health outcomes were projected over a 10-year time horizon and discounted at 3% per year. Costs for drug acquisition, PD-L1 testing, drug administration and disease management were used. Sensitivity analyses were conducted to evaluate the robustness of results. RESULTS: The BTS approach led to an increase of 0.29 QALYs at an additional cost of Hong Kong dollars (HK$) 249,077 (US$31,933) compared with platinum doublet chemotherapy, resulting in an ICER of HK$865,189 (US$110,922) per QALY gained. This is lower than the World Health Organization cost-effectiveness threshold of three times the 2016 gross domestic product (GDP) per capita for Hong Kong of HK$1017,819 (US$130,490). Probabilistic sensitivity analyses showed a 59.4% chance that the ICER would be below this threshold. CONCLUSION: First-line treatment with pembrolizumab in a BTS to identify patients with NSCLC with PD-L1 TPS ≥ 50% can be considered cost effective in Hong Kong compared with platinum doublet chemotherapy based on a three-times GDP per capita threshold. However, local data on clinical efficacy and safety were not available to estimate overall survival (OS) and progression-free survival (PFS) specific to patients with NSCLC in Hong Kong. Further, uncertainty is inherent in the survival projections/extrapolation of PFS and OS beyond the trial period, and future research may help to further inform these parameters.

Cost-effectiveness analysis of FOLFOX4 and sorafenib for the treatment of advanced hepatocellular carcinoma in China.

OBJECTIVES: Hepatocellular carcinoma (HCC) is a leading cause of cancer-related deaths globally. In China, sorafenib and oxaliplatin plus infusional-fluorouracil/leucovorin (FOLFOX4) are approved for the systemic treatment of advanced HCC. This study compared the cost-effectiveness of these therapies from a healthcare system perspective and a patient perspectives. METHODS: A Markov model was constructed using overall and progression-free survival rates and adverse event (AE) rate from two randomized controlled studies of advanced HCC patients from Asia: EACH for FOLFOX4 and ORIENTAL for sorafenib. The patients in the Markov model were followed until death, the length of each Markov cycle was 1 month, and the survival was adjusted for quality-adjusted life years (QALYs). Direct medical costs included costs of therapies, AE treatment, general ward and tests. Costs were derived from published sources, interviews with oncologists and hospital data from China. One-way and probabilistic sensitivity analyses (PSA) were performed to test the robustness of the results. RESULTS: From the healthcare system perspective, FOLFOX4 dominated sorafenib with lower therapy costs (FOLFOX4: US$ 6972; sorafenib: US$ 12,289), lower direct medical costs (FOLFOX4: US$ 8428; sorafenib: US$ 12,798), and higher QALYs (FOLFOX4: 0.42; sorafenib: 0.38) per patient. This result was robust according to comprehensive one-way sensitivity analyses. According to the PSA, at the cost-effectiveness threshold for China (3 × GDP, US$ 22,073), FOLFOX4 should be chosen in 63.9% of simulations. From the patient perspective, FOLFOX4 also dominated sorafenib. CONCLUSIONS: The study results indicate that FOLFOX4 dominates sorafenib because it appears to provide higher effectiveness with significantly lower costs in treating Chinese advanced HCC patients.

Societal implications of medical insurance coverage for imatinib as first-line treatment of chronic myeloid leukemia in China: a cost-effectiveness analysis.

OBJECTIVES: Imatinib (Glivec) and nilotinib (Tasigna) have been covered by critical disease insurance in Jiangsu province of China since 2013, which changed local treatment patterns and outcomes of patients with chronic myeloid leukemia (CML). This study evaluated the long-term cost-effectiveness of insurance coverage with imatinib as the first-line treatment for patients with CML in China from a societal perspective. METHODS: A decision-analytic model based on previously published and real-world evidence was applied to simulate and evaluate the lifetime clinical and economic outcomes associated with CML treatments before and after imatinib was covered by medical insurance. Incremental cost-effectiveness ratio (ICER) was calculated with both costs and quality-adjusted life years (QALYs) discounted at 3% annually. Different assumptions of treatment benefits and costs were taken to address uncertainties and were tested with sensitivity analyses. RESULTS: In base case analysis, both cost and effectiveness of CML treatments increased after imatinib was covered by the medical insurance; on average, the incremental QALY and cost were 5.5 and ¥277,030 per patient in lifetime, respectively. The ICER of insurance coverage with imatinib was ¥50,641, which is less than the GDP per capita of China. Monte Carlo simulation resulted in the estimate of 100% probability that the insurance coverage of imatinib is cost-effective. Total cost was substantially saved at 5 years after patients initiated imatinib treatment with insurance coverage compared to no insurance coverage, the saved cost at 5 years was ¥99,565, which included the cost savings from both direct (e.g. cost of bone marrow or stem cell transplant) and indirect costs (e.g. productivity loss of patients and care-givers). CONCLUSIONS: The insurance coverage of imatinib is very cost-effective in China, according to the local cost and clinical data in Jiangsu province. More importantly, the insurance coverage of imatinib and nilotinib have changed the treatment patterns of CML patients, thus dramatically increasing life expectancy and quality-of-life (QoL) saving on productivity losses for both CML patients and their caregivers.

The impact of medical insurance coverage and molecular monitoring frequency on outcomes in chronic myeloid leukemia: real-world evidence in China.

OBJECTIVES: Imatinib (Glivec) has been covered by critical disease insurance for treatment of chronic myeloid leukemia (CML) in Jiangsu province of China since 2013. Further, free molecular monitoring has been provided to patients at top clinical centers as part of a pilot study that has changed the local treatment pattern and outcomes of patients with CML. This study evaluates the impact of medical insurance coverage and the molecular monitoring frequency on outcomes of patients with CML treated at a central hospital in Jiangsu, China, according to patient-level data. METHODS: The study investigated 335 CML patients receiving medical treatment in a central hospital between January 1, 2011 and December 31, 2014. Demographic and clinical characteristics were extracted from the patients' clinical records. Univariate and multivariate analyses using the logistic regression model were performed to identify the differences in outcomes of major molecular response (MMR) or complete cytogenetic response (CCyR) between patients who were insured vs uninsured, or between patients with frequency of PCR monitoring ≤2 times vs ≥3 times per year. RESULTS: Both the achievement of MMR (BCR-ABLIS ≤0.1%) (50.4% vs 37.5%) and CCyR (80.7% vs 62.8%) at 12 months have shown significant differences that favored patients with insurance coverage of imatinib, while there was no significant difference in the outcome of BCR-ABLIS ≤1% between insured and non-insured groups (56.0% vs 51.3%) at 6 months. The long-term results at 24 months demonstrated that there was a statistically significant difference in MMR rates between the group with 3 or more PCR monitoring tests per year and the group of patients with 2 or less PCR tests per year (76.9% vs 52.2%). CONCLUSIONS: The study findings suggest that CML patients benefit from insurance coverage of imatinib and higher frequency (≥3) of regularly scheduled molecular monitoring PCR in China.

A Cost-Effectiveness Analysis of Clopidogrel for Patients with Non-ST-Segment Elevation Acute Coronary Syndrome in China.

INTRODUCTION: There are a number of economic evaluation studies of clopidogrel for patients with non-ST-segment elevation acute coronary syndrome (NSTEACS) published from the perspective of multiple countries in recent years. However, relevant research is quite limited in China. We aimed to estimate the long-term cost effectiveness for up to 1-year treatment with clopidogrel plus acetylsalicylic acid (ASA) versus ASA alone for NSTEACS from the public payer perspective in China. METHODS: This analysis used a Markov model to simulate a cohort of patients for quality-adjusted life years (QALYs) gained and incremental cost for lifetime horizon. Based on the primary event rates, adherence rate, and mortality derived from the CURE trial, hazard functions obtained from published literature were used to extrapolate the overall survival to lifetime horizon. Resource utilization, hospitalization, medication costs, and utility values were estimated from official reports, published literature, and analysis of the patient-level insurance data in China. To assess the impact of parameters' uncertainty on cost-effectiveness results, one-way sensitivity analyses were undertaken for key parameters, and probabilistic sensitivity analysis (PSA) was conducted using the Monte Carlo simulation. RESULTS: The therapy of clopidogrel plus ASA is a cost-effective option in comparison with ASA alone for the treatment of NSTEACS in China, leading to 0.0548 life years (LYs) and 0.0518 QALYs gained per patient. From the public payer perspective in China, clopidogrel plus ASA is associated with an incremental cost of 43,340 China Yuan (CNY) per QALY gained and 41,030 CNY per LY gained (discounting at 3.5% per year). PSA results demonstrated that 88% of simulations were lower than the cost-effectiveness threshold of 150,721 CYN per QALY gained. Based on the one-way sensitivity analysis, results are most sensitive to price of clopidogrel, but remain well below this threshold. CONCLUSION: This analysis suggests that treatment with clopidogrel plus ASA for up to 1 year for patients with NSTEACS is cost effective in the local context of China from a public payers' perspective. FUNDING: Sanofi China.

Oseltamivir Treatment for Children with Influenza-Like Illness in China: A Cost-Effectiveness Analysis.

BACKGROUND: Influenza is a common viral respiratory infection that causes epidemics and pandemics in the human population. Oseltamivir is a neuraminidase inhibitor-a new class of antiviral therapy for influenza. Although its efficacy and safety have been established, there is uncertainty regarding whether influenza-like illness (ILI) in children is best managed by oseltamivir at the onset of illness, and its cost-effectiveness in children has not been studied in China. OBJECTIVE: To evaluate the cost-effectiveness of post rapid influenza diagnostic test (RIDT) treatment with oseltamivir and empiric treatment with oseltamivir comparing with no antiviral therapy against influenza for children with ILI. METHODS: We developed a decision-analytic model based on previously published evidence to simulate and evaluate 1-year potential clinical and economic outcomes associated with three managing strategies for children presenting with symptoms of influenza. Model inputs were derived from literature and expert opinion of clinical practice and research in China. Outcome measures included costs and quality-adjusted life year (QALY). All the interventions were compared with incremental cost-effectiveness ratios (ICER). RESULTS: In base case analysis, empiric treatment with oseltamivir consistently produced the greatest gains in QALY. When compared with no antiviral therapy, the empiric treatment with oseltamivir strategy is very cost effective with an ICER of RMB 4,438. When compared with the post RIDT treatment with oseltamivir, the empiric treatment with oseltamivir strategy is dominant. Probabilistic sensitivity analysis projected that there is a 100% probability that empiric oseltamivir treatment would be considered as a very cost-effective strategy compared to the no antiviral therapy, according to the WHO recommendations for cost-effectiveness thresholds. The same was concluded with 99% probability for empiric oseltamivir treatment being a very cost-effective strategy compared to the post RIDT treatment with oseltamivir. CONCLUSION: In the Chinese setting of current health system, our modelling based simulation analysis suggests that empiric treatment with oseltamivir to be a cost-saving and very cost-effective strategy in managing children with ILI.

Epidemiology of dyslipidemia in Chinese adults: meta-analysis of prevalence, awareness, treatment, and control.

BACKGROUND: Numerous epidemiology studies on dyslipidemia have been conducted in China. However, a nationally representative estimate for dyslipidemia prevalence is lacking. The aim of this study is to appraise the nationwide prevalence, awareness, treatment, and control rates of dyslipidemia in adults in China. METHODS: We performed a systematic review of the related observational studies published since 2003 by searching English and Chinese literature databases. Meta-analyses were conducted in eligible studies using a random effect model to summarize the dyslipidemia prevalence, awareness, treatment, and control rates. Heterogeneity and publication bias were analyzed. Sensitivity analyses were performed to explain heterogeneity and examine the impact of study quality on the results of meta-analyses. RESULTS: Thirty-eight papers were included for meta-analyses, with a total sample size of 387,825. The prevalence, awareness, treatment, and control rates of dyslipidemia were 41.9% (95% CI: 37.7% - 46.2%), 24.4% (95% CI: 14.4% - 38.4%), 8.8% (95% CI: 7.7% - 10.0%), and 4.3% (95% CI: 4.1% - 4.5%), respectively. The prevalence of hypercholesterolemia, hypertriglyceridemia, mixed hyperlipidemia, low levels of high-density lipoprotein cholesterol, and high levels of low-density lipoprotein cholesterol were 10.1% (95% CI: 5.8% - 16.9%), 17.7% (95% CI: 14.0% - 22.1%), 5.1% (95% CI: 3.1% - 8.2%), 11.0% (95% CI: 8.0% - 15.0%), and 8.8% (95% CI: 4.1% - 17.8%), respectively. Sensitivity analyses revealed that males had a higher prevalence of dyslipidemia (43.2%) than females (35.6%). Study samples of age 30 and above in the eastern region tended to have higher prevalence of dyslipidemia. The quality of the studies has a slight impact on the pooled estimates. CONCLUSIONS: The overall pooled prevalence of dyslipidemia in Chinese adults was estimated to be 41.9%, with males having a higher rate than females.

Ranibizumab (Lucentis) versus bevacizumab (Avastin): modelling cost effectiveness.

Two new drugs provide startling benefits in the treatment of age-related macular degeneration (AMD). The clinical and cost effectiveness of ranibizumab (Lucentis) was compared to that of bevacizumab (Avastin), which costs up to 100 times less. A cost effectiveness model was developed to assess the cost per quality adjusted life year (QALY) over 10 years. For predominantly classic AMD, the efficacy of bevacizumab relative to ranibizumab would have to be around 40% for the latter to achieve 30 k pounds per QALY, a NICE threshold. Similar but worse results applied to the other main forms of AMD, minimally occult and occult with no classic lesions. The price of ranibizumab would have to be drastically reduced for it to be cost effective. Continued unlicensed use of bevacizumab raises ethical, legal and policy questions. Public pressure may be the most potent weapon in persuading Genentech to license bevacizumab for AMD.