Maximizing the cost-effectiveness of cervical screening in the context of routine HPV vaccination by optimizing screening strategies with respect to vaccine uptake: a modeling analysis.

BACKGROUND: Regarding primary and secondary cervical cancer prevention, the World Health Organization proposed the cervical cancer elimination strategy that requires countries to achieve 90% uptake of human papillomavirus (HPV) vaccines and 70% screening uptake. The optimal cervical screening strategy is likely different for unvaccinated and vaccinated cohorts upon national HPV immunization. However, health authorities typically only provide a one-size-fits-all recommendation for the general population. We aimed to evaluate the cost-effectiveness for determining the optimal screening strategies for vaccinated and unvaccinated cohorts. METHODS: We considered the women population in Hong Kong which has a unique HPV infection and cervical cancer epidemiology compared to other regions in China and Asia. We used mathematical models which comprise a deterministic age-structured compartmental dynamic component and a stochastic individual-based cohort component to evaluate the cost-effectiveness of screening strategies for cervical screening. Following the recommendations in local guidelines in Hong Kong, we considered strategies that involved cytology, HPV testing, or co-testing as primary cervical screening. We also explored the impacts of adopting alternative de-intensified strategies for vaccinated cohorts. The 3-year cytology screening was used as the base comparator while no screening was also considered for vaccinated cohorts. Women's lifetime life years, quality-adjusted life years, and costs of screening and treatment were estimated from the societal perspective based on the year 2022 and were discounted by 3% annually. Incremental cost-effectiveness ratios (ICERs) were compared to a willingness to pay (WTP) threshold of one gross domestic product per capita (US $47,792). Probabilistic and one-way sensitivity analyses were conducted. RESULTS: Among unvaccinated cohorts, the strategy that adds reflex HPV to triage mild cytology abnormality generated more life years saved than cytology-only screening and could be a cost-effective alternative. Among vaccinated cohorts, when vaccine uptake was 85% (based on the uptake in 2022), all guideline-based strategies (including the cytology-only screening) had ICERs above the WTP threshold when compared with no screening if the vaccine-induced protection duration was 20 years or longer. Under the same conditions, HPV testing with genotyping triage had ICERs (compared with no screening) below the WTP threshold if the routine screening interval was lengthened to 10 and 15 years or screening was initiated at ages 30 and 35 years. CONCLUSIONS: HPV testing is a cost-effective alternative to cytology for vaccinated cohorts, and the associated optimal screening frequency depends on vaccine uptake. Health authorities should optimize screening recommendations by accounting for population vaccine uptake.

Cost-Effectiveness of Anti-Epidermal Growth Factor Receptor Therapy Versus Bevacizumab in KRAS Wild-Type (WT), Pan-RAS WT, and Pan-RAS WT Left-Sided Metastatic Colorectal Cancer.

OBJECTIVES: We aimed to compare the economic value of chemotherapy plus anti-epidermal growth factor receptor (anti-EGFR) monoclonal antibody (mAb) against chemotherapy with bevacizumab (Bev, an anti-vascular endothelial growth factor mAb) as first-line treatment in KRAS wild-type (WT), pan-RAS WT and pan-RAS WT left-sided metastatic colorectal cancer (mCRC) patients from the Hong Kong societal perspective. MATERIALS AND METHODS: We developed Markov models and 10-year horizon to estimate costs, quality-adjusted life years (QALYs), and incremental cost-effectiveness ratio (ICER) of chemotherapy plus anti-EGFR therapy against chemotherapy plus Bev in KRAS WT, pan-RAS WT, and pan-RAS WT left-sided mCRC. We considered two times of the local gross domestic product per capita (GDPpc) as the willingness-to-pay (WTP) threshold (2× GDPpc; US$97,832). RESULTS: Adding anti-EGFR mAb to chemotherapy provides additional 0.24 (95% confidence interval [CI] 0.19-0.29), 0.32 (95% CI 0.27-0.37), and 0.57 (95% CI 0.49-0.63) QALY compared to adding Bev in KRAS WT, pan-RAS WT, and left-sided pan-RAS WT mCRC populations respectively. The corresponding ICER is US$106,847 (95% CI 87,806-134,523), US$88,565 (95% CI 75,678-105,871), US$76,537 (95% CI 67,794-87,917) per QALY gained, respectively. CONCLUSIONS: Anti-EGFR therapy is more cost-effective than Bev as a first-line targeted therapy in left-sided pan-RAS WT and pan-RAS WT, with ICER

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.

A Cost-Effectiveness Analysis of Systemic Therapy for Metastatic Hormone-Sensitive Prostate Cancer.

BACKGROUND: Currently, approved first-line treatment options of metastatic hormone-sensitive prostate cancer (mHSPC) include (1) androgen deprivation therapy (ADT) alone, ADT plus one of the following: (2) docetaxel, (3) abiraterone, (4) enzalutamide, and (5) apalutamide. The high cost of novel androgen receptor pathway inhibitors warrants an understanding of the combinations' value by considering both efficacy and cost. OBJECTIVE: This study aimed to compare the cost-effectiveness of these five treatment options in mHSPC from the US payer perspective to guide treatment sequence. METHODS: A Markov model was developed to compare the lifetime cost and effectiveness of these five first-line treatment options for mHSPC using outcomes data from published literature. Health outcomes were measured in life-years and quality-adjusted life-years (QALYs). Drug costs were obtained from the Veterans Affairs Pharmaceutical Catalog. We extrapolated survival beyond closure of the trials. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Life-years, QALYs, lifetime costs, and incremental cost-effectiveness ratios (ICERs) were estimated. Univariable, 2-way, and probabilistic sensitivity analyses were performed to evaluate parameter uncertainty. A willingness-to-pay (WTP) threshold of US$100,000 per QALY was used. RESULTS: Compared to ADT alone, docetaxel plus ADT provided a 0.28 QALY gain at an ICER of US$12,870 per QALY. Abiraterone plus ADT provided an additional 1.70 QALYs against docetaxel plus ADT, with an ICER of US$38,897 per QALY. Compared to abiraterone plus ADT, enzalutamide plus ADT provided an additional 0.87 QALYs at an ICER of US$509,813 per QALY. Apalutamide plus ADT was strongly dominated by enzalutamide plus ADT. Given the WTP threshold of US$100,000 per QALY, abiraterone plus ADT represented high-value health care. CONCLUSIONS: Abiraterone plus ADT is the preferred treatment option for men with mHSPC at a WTP threshold of US$100,000 per QALY.

Cost-effectiveness analysis of Abiraterone Acetate versus Docetaxel in the management of metastatic castration-sensitive prostate cancer: Hong Kong's perspective.

BACKGROUND: Several randomized control trials (RCTs) have showed that adding either abiraterone acetate (AA) or docetaxel (D) to androgen-deprivation therapy (ADT) improves survival of metastatic castration-sensitive prostate cancer patients (mCSPC). Yet, the cost-effectiveness of these treatment options has not been fully compared under Hong Kong's setting. This cost-effectiveness analysis (CEA) serves as the first study in Hong Kong to compare the economic value of these two combinations ADT + AA vs. ADT + D. METHODS: A deterministic Markov model is used to project cost-effectiveness of each treatment until death. Survival curves for progression/death were extracted and digitized from the five RCTs (CHAARTED, LATITUDE, two STAMPEDE (2016/2017), and GETUG-AFU15). Clinically significant adverse events (AEs) were modeled; utility values were obtained from the literature. Primary outcomes were the quality-adjusted life years (QALYs) and incremental cost-effectiveness ratio (ICER). We used the societal perspective from Hong Kong and considered three times of local gross domestic product per capita (GDPpc) as the willingness-to-pay (WTP) threshold (i.e., US$138,649). We estimated the break-even cost of AA in case ADT + AA is not a cost-effective strategy under this WTP threshold. While considering the standard AA dosage (1000 mg) as the main analysis, we also examined the potential impact of the low-dose AA (250 mg) strategy. RESULTS: Integrating simulations with probabilistic sensitivity analysis, ADT + D returns 0.79 (median; 95% credible interval 0.56-0.97) QALY with an ICER of US$14,397/QALY ($7824-22,632) compared to ADT-alone. A head-to-head comparison indicates that ADT + AA further gains 0.79 (0.45-1.17) QALY but with an ICER of $361,439/QALY ($260,615-599,683) when compared to ADT + D. Considering three times of GDPpc as WTP threshold, ADT + D is more cost-effective in all simulations; while ADT + AA is more cost-effective than ADT + D only if the cost of AA is reduced by at least 63%. The low-dose AA (250 mg) strategy is potentially cost-effective when it generates equivalent efficacy as the standard dosage (1000 mg). CONCLUSIONS: ADT + D is therefore shown to be a more cost-effective strategy than ADT + AA in metastatic castration-sensitive prostate cancer patients in developed economies. Addition of AA substantially improved QALY compared to D but at a significant cost.

Global comparison of cancer outcomes: standardization and correlation with healthcare expenditures.

BACKGROUND: Cancer outcomes vary widely among different countries. However, comparisons of cost-effectiveness and cost-efficiency of different systems are complex because the incidences of different cancers vary across countries and their chances of cure also differ substantially. We aim to propose a new standardized method for global comparison and to explore its relationship with economic indicators. METHODS: Cancer statistics from all 184 countries and 27 cancers listed in GLOBOCAN 2012 were analyzed. The complement of age-standardized mortality/incidence ratio [1 - (ASM/ASI)] was taken as the proxy relative survival (RS). Accounting for various country-specific cancer patterns, the cancer site-standardized proxy RS (proxy SS-RS) of individual countries were calculated by weighting the proportion of specific cancer sites as compared with the global pattern of incidence. Economic indicators of different countries listed by the World Bank were correlated with corresponding proxy SS-RS. RESULTS: Substantial variation in site-specific survival and new case distribution supported the use of proxy SS-RS, which ranged from 0.124 to 0.622 (median 0.359). The median total health expenditure per capita (HEpc) increased from US$44 for countries with proxy SS-RS < 0.25, to US$4643 for countries with proxy SS-RS ≥0.55. Results from logarithmic regression model showed exponential increase in total HEpc for better outcome. The expenditure varied widely among different strata, with the widest difference observed among countries with SS-RS ≥0.55 (total HEpc US$1412-$9361). CONCLUSIONS: Similar to age-standardization, cancer site-standardization adjusted for variation in pattern of cancer incidence provides the best available and feasible strategies for comparing cancer survivals across countries globally. Furthermore, cancer outcome correlated significantly with economic indicators and the amount of HEpc escalated exponentially. Our findings call for more in-depth studies applying cancer-site standardization to provide essential data for sharing of experience and urgent actions by policy makers to develop comprehensive and financially sustainable cancer plan for greater equity.

Simultaneously characterizing the comparative economics of routine female adolescent nonavalent human papillomavirus (HPV) vaccination and assortativity of sexual mixing in Hong Kong Chinese: a modeling analysis.

BACKGROUND: Although routine vaccination of females before sexual debut against human papillomavirus (HPV) has been found to be cost-effective around the world, its cost-benefit has rarely been examined. We evaluate both the cost-effectiveness and cost-benefit of routine female adolescent nonavalent HPV vaccination in Hong Kong to guide its policy, and by extension that of mainland China, on HPV vaccination. One major obstacle is the lack of data on assortativity of sexual mixing. Such difficulty could be overcome by inferring sexual mixing parameters from HPV epidemiologic data. METHODS: We use an age-structured transmission model coupled with stochastic individual-based simulations to estimate the health and economic impact of routine nonavalent HPV vaccination for girls at age 12 on cervical cancer burden and consider vaccine uptake at 25%, 50%, and 75% with at least 20 years of vaccine protection. Bayesian inference was employed to parameterize the model using local data on HPV prevalence and cervical cancer incidence. We use the human capital approach in the cost-benefit analysis (CBA) and GDP per capita as the indicative willingness-to-pay threshold in the cost-effectiveness analysis (CEA). Finally, we estimate the threshold vaccine cost (TVC), which is the maximum cost for fully vaccinating one girl at which routine female adolescent nonavalent HPV vaccination is cost-beneficial or cost-effective. RESULTS: As vaccine uptake increased, TVC decreased (i.e., economically more stringent) in the CBA but increased in the CEA. When vaccine uptake was 75% and the vaccine provided only 20 years of protection, the TVC was US$444 ($373-506) and $689 ($646-734) in the CBA and CEA, respectively, increasing by approximately 2-4% if vaccine protection was assumed lifelong. TVC is likely to be far higher when non-cervical diseases are included. The inferred sexual mixing parameters suggest that sexual mixing in Hong Kong is highly assortative by both age and sexual activity level. CONCLUSIONS: Routine HPV vaccination of 12-year-old females is highly likely to be cost-beneficial and cost-effective in Hong Kong. Inference of sexual mixing parameters from epidemiologic data of prevalent sexually transmitted diseases (i.e., HPV, chlamydia, etc.) is a potentially fruitful but largely untapped methodology for understanding sexual behaviors in the population.