Cost-effectiveness of cytomegalovirus vaccination for females in China: A decision-analytical Markov study.

BACKGROUND: The global burden of disease caused by congenital cytomegalovirus (CMV) infection is high. Previous modeling studies have suggested that CMV vaccination may be cost-effective in developed countries. Congenital CMV infection is more likely driven by maternal non-primary infection in China. We aimed to measure the effectiveness and cost-effectiveness of population-level CMV vaccination in Chinese females. METHODS: A decision tree Markov model was developed to simulate potential CMV vaccination strategies in a multi-cohort setting, with a population size of 1,000,000 each for the infant, adolescent (10-year-old) and young adult (20-year-old) cohorts. The hypothetical vaccines were assumed to have 50% efficacy, 20 years of protection, 70% coverage, at a price of US$120/dose for base-case analysis. Costs and disability-adjusted life years (DALYs) were discounted by 3% per year and the vaccination would be considered cost-effective if an incremental cost-effectiveness ratio (ICER) was lower than 2021 Chinese per capita GDP (US$12,500). FINDINGS: For the pre-infection (PRI) vaccine efficacy type, the adolescent strategy was the most cost-effective, with an ICER of US$12,213 (12,134 to 12,291) pre DALY averted, compared with the next best strategy (young adult strategy). For pre- and post-infection (P&PI) efficacy type, the young adult strategy was the most cost-effective as it was cost-saving. In one-way analysis varying the PRI vaccine price, the infant strategy, adolescent strategy and the young adult strategy would be a dominant strategy over others if the vaccine cost ≤US$60, US$61-121 and US$122-251 per dose respectively. In contrast, the young adult strategy continued to be the preferred strategy until the P&PI vaccine price exceeded US$226/dose. Our main results were robust under a wide variety of sensitivity analyses and scenario analyses. INTERPRETATION: CMV vaccination for females would be cost-effective and even cost-saving in China. Our findings had public health implications for control of CMV diseases.

Incorporating productivity loss in health economic evaluations: a review of guidelines and practices worldwide for research agenda in China.

INTRODUCTION: Productivity loss may contribute to a large proportion of costs of health conditions in an economic evaluation from a societal perspective, but there is currently a lack of methodological consensus on how productivity loss should be measured and valued. Despite the research progress surrounding this issue in other countries, it has been rarely discussed in China. METHODS: We reviewed the official guidelines on economic evaluations in different countries and regions and screened the literature to summarise the extent to which productivity loss was incorporated in economic evaluations and the underlying methodological challenges. RESULTS: A total of 48 guidelines from 46 countries/regions were included. Although 32 (67%) guidelines recommend excluding productivity loss in the base case analysis, 23 (48%) guidelines recommend including productivity loss in the base case or additional analyses. Through a review of systematic reviews and the economic evaluation studies included in these reviews, we found that the average probability of incorporating productivity loss in an economic evaluation was 10.2%. Among the economic evaluations (n=478) that explicitly considered productivity loss, most (n=455) considered losses from paid work, while only a few studies (n=23) considered unpaid work losses. Recognising the existing methodological challenges and the specific context of China, we proposed a practical research agenda and a disease list for progress on this topic, including the development of the disease list comprehensively consisting of health conditions where the productivity loss should be incorporated into economic evaluations. CONCLUSION: An increasing number of guidelines recommend the inclusion of productivity loss in the base case or additional analyses of economic evaluation. We optimistically expect that more Chinese researchers notice the importance of incorporating productivity loss in economic evaluations and anticipate guidelines that may be suitable for Chinese practitioners and decision-makers that facilitate the advancement of research on productivity loss measurement and valuation.

Direct comparison of LC-MS/MS and RIA methods for the pharmacokinetics assessment of human insulin in preclinical development.

Insulin is an effective therapeutic for diabetes, and the level of insulin in vivo is directly related to the health of diabetic patients. Traditionally, the concentrations of insulin in vivo are determined by the radioimmunoassay (RIA) method. In this study, we developed an LC-MS/MS method for the quantification of human insulin in dog plasma and directly compared the RIA and LC-MS/MS methods. Our LC-MS/MS method exhibited superior accuracy, efficiency and cost-effective for the pharmacokinetic (PK) assessment of human insulin. The LC-MS/MS method can quantitate human insulin and canine insulin simultaneously without cross-reactivity, making the analysis more efficient. The LLOQ of our LC-MS/MS method was 38.5 pg/mL, which was necessary to fully describe the PK profiles of endogenous and exogenous insulin in vivo. The direct comparison of PK data obtained from the two methods demonstrated that LC-MS/MS could be an alternative to the RIA method and should be widely used for the quantification of insulin drugs, especially in preclinical studies.

[Simultaneous determination of clevidipine butyrate and its metabolite clevidipine acid in dog blood by liquid chromatography-tandem mass spectrometry].

A rapid, sensitive and simple liquid chromatography-tandem mass spectrometry (LC-MS/MS) method was developed and validated for the simultaneous determination of clevidipine butyrate and its primary metabolite clevidipine acid in dog blood. After one-step protein precipitation with methanol, the chromatographic separation was carried out on an Ecosil C18 column (150 mm x 4.6 mm, 5 µm) with a gradient mobile phase consisting of methanol and 5 mmol · L(-1) ammonium formate. A chromatographic total run time of 13.0 min was achieved. The quantitation analysis was performed using multiple reaction monitoring (MRM) at the specific ion transitions of m/z 454.1 [M-H]- --> m/z 234.1 for clevidipine butyrate, m/z 354.0 [M-H]- --> m/z 208.0 for clevidipine acid and m/z 256.1 [M-H]- --> m/z 227.1 for elofesalamide (internal standard, IS) in the negative ion mode with electrospray ionization (ESI) source. The linear calibration curves for clevidipine butyrate and clevidipine acid were obtained in the concentration ranges of 0.5-100 ng · mL and 1-200 ng · mL(-1), separately. The lower limit of quantification of clevidipine butyrate and clevidipine acid were 0.5 ng · mL(-1) and 1 ng · mL(-1). The intra and inter-assay precisions were all below 12.9%, the accuracies were all in standard ranges. Stability testing indicated that clevidipine butyrate and clevidipine acid in dog blood with the addition of denaturant methanol was stable under various processing and/or handling conditions. The validated method has been successfully applied to a pharmacokinetic study of clevidipine butyrate injection to 8 healthy Beagle dogs following intravenous infusion at a flow rate of 5 mg · h(-1) for 0.5 h.