Cost-Effectiveness of 4CMenB Infant Vaccination in England: A Comprehensive Valuation Considering the Broad Impact of Serogroup B Invasive Meningococcal Disease.

OBJECTIVES: This cost-effectiveness analysis (CEA) of 4CMenB infant vaccination in England comprehensively considers the broad burden of serogroup B invasive meningococcal disease (MenB IMD), which has not been considered, or was only partially considered in previous CEAs. METHODS: A review of previous MenB vaccination CEAs was conducted to identify aspects considered in the evaluation of costs and health outcomes of the disease burden of MenB IMD. To inform the model structure and comprehensive analysis, the aspects were grouped into 5 categories. A stepwise analysis was conducted to analyze the impact of each category, and the more comprehensive consideration of disease burden, on the incremental cost-effectiveness ratio (ICER). RESULTS: MenB IMD incidence decreased by 46.0% in infants and children 0-4 years old within 5 years after introduction of the program. Stepwise inclusion of the 5 disease burden categories to a conventional narrow CEA setting reduced the ICER from £360 595 to £18 645-that is, considering the impact of all 5 categories, 4CMenB infant vaccination is cost-effective at a threshold of £20 000 per QALY gained. CONCLUSIONS: When considering comprehensively the MenB IMD burden, 4CMenB infant vaccination can be cost-effective, a finding contrary to previous CEAs. This analysis allows policy decision-makers globally to infer the impact of current disease burden considerations on the cost-effectiveness and the comprehensive assessment necessary for MenB IMD. Although this comprehensive CEA can help inform decision making today, it may be limited in capturing the full disease burden and complex interactions of health and economics of MenB IMD.

Modelling the impact of 4CMenB and MenACWY meningococcal combined vaccination strategies including potential 4CMenB cross-protection: An application to England.

Invasive meningococcal disease (IMD), an uncommon but severe disease, affects mainly infants, young children and adolescents. Meningococcal B (4CMenB) and ACWY (MenACWY) vaccines targeting IMD-causing serogroups B and A, C, W and Y, respectively are available for these mostly-affected age-groups. The objective was to assess the impact of 4CMenB and/or MenACWY vaccination strategies on IMD in England, considering MenACWY carriage protection and potential cross-protection of 4CMenB against non-B serogroups. A novel dynamic transmission model was developed, accounting for vaccine characteristics, with separate variables for meningococcal carriage and IMD for three groups: B; ACWY; and 'Other' mostly non-pathogenic serogroups. A dynamic force of infection is assumed for each group. The model analysis uses data from England before 2015 (when 4CMenB and MenACWY were introduced), and accounts for existing MenC vaccination impact. Compared with no vaccination, the smallest decrease in IMD cases is observed for MenACWY strategies (toddler and/or adolescent). 4CMenB (infant or infant/adolescent), alone or with MenACWY, always results in the most rapid and steep decline in IMD cases. Combined strategies with adolescent 4CMenB result in the largest decrease in IMD cases, whereas adding MenACWY for toddlers has a minor impact. With potential 4CMenB cross-protection, 4CMenB infant strategy has a notable impact on reduction of MenW and MenY IMD cases in strategies where MenACWY toddler and/or adolescent vaccination is absent. This novel model allows for analysis of combined 4CMenB and MenACWY strategies including potential 4CMenB cross-protection. In settings comparable to England, a comprehensive meningococcal vaccination programme should include infant 4CMenB as essential building block. Decisions to include MenACWY toddler programmes should consider herd effects of MenACWY adolescent programmes and 4CMenB potential cross-protection effects. Extending 4CMenB infant and MenACWY adolescent programmes with a 4CMenB adolescent programme allows for the largest overall reduction in IMD cases.

Risk factors for cervical cancer in women in China: A meta-model.

OBJECTIVES: Cervical cancer is a leading cause of cancer-related mortality in women in China. This analysis is a quantitative evidence synthesis pooling information about each cervical cancer risk factor. METHODS: A meta-model was developed to estimate the risk of cervical cancer for a woman aged 18-85 years in Mainland China based on her risk profile at the time of assessment. The meta-model was built using findings of a systematic literature review that identified 21 case-control studies reporting data on 105 groups of cervical cancer risk factors in Chinese women. Extracted risk factors were ranked, and 17 were selected by Chinese clinical experts for inclusion in the meta-model. Risk equations were developed for each selected study. Predicted risks for each study were dependent on the risk profile under consideration and study-specific risks were pooled to an overall risk estimate using a random-effects meta-analysis. Sensitivity analysis was conducted using 100 artificial patient profiles (in the absence of patient data). RESULTS: Predicted risks for the 100 profiles suggested that the model had good face validity and could differentiate between high and non-high cervical cancer risk profiles. CONCLUSION: This innovative meta-model approach assesses cervical cancer risk in Chinese women from a holistic perspective and could be adapted for other diseases and settings.

An algorithm to generate correlated input-parameters to be used in probabilistic sensitivity analyses.

Background: Assessment of uncertainty in cost-effectiveness analyses (CEAs) is paramount for decision-making. Probabilistic sensitivity analysis (PSA) estimates uncertainty by varying all input parameters simultaneously within predefined ranges; however, PSA often ignores correlations between parameters. Objective: To implement an efficient algorithm that integrates parameter correlation in PSA. Study design: An algorithm based on Cholesky decomposition was developed to generate multivariate non-normal parameter distributions for the age-dependent incidence of herpes zoster (HZ). The algorithm was implemented in an HZ CEA model and evaluated for gamma and beta distributions. The incremental cost-effectiveness ratio (ICER) and the probability of being cost-effective at a given ICER threshold were calculated for different levels of correlation. Five thousand Monte Carlo simulations were carried out. Results: Correlation coefficients between parameters sampled from the distribution generated by the algorithm matched the desired correlations for both distribution functions. With correlations set to 0.0, 0.5, and 0.9, 90% of the simulations showed ICERs below $25,000, $33,000, and $38,000 per quality-adjusted life-year (QALY), respectively, varying incidence only; and below $38,000, $48,000, and $58,000 per QALY, respectively, varying most parameters. Conclusion: Parameter correlation may impact the uncertainty of CEA results. We implemented an efficient method for generating correlated non-normal distributions for use in PSA.

Cost-effectiveness of the recombinant zoster vaccine in the German population aged ≥60 years old.

Each year, around 300,000 Herpes Zoster (HZ) cases are observed in the German population, resulting in costs over €182 million to society. The objective of this study was to estimate the potential public health and economic impact of the new Adjuvanted Recombinant Zoster Vaccine (RZV, Shingrix) in the German population ≥ 60 years of age (YOA) and to identify the optimal age of vaccination. We used a static, multi-cohort Markov model that followed a hypothetical cohort of 1 million people ≥ 60 YOA life-long after vaccination using German-specific inputs. Both costs and outcomes were discounted at 3%, the incremental cost-effectiveness ratio (ICER) was calculated based on the societal perspective. The coverage of RZV was set at 40% with a second-dose compliance of 70%. Vaccinating the population aged ≥ 60 YOA would result in 45,000 HZ cases avoided, 1,713 quality-adjusted life years (QALYs) gained at a total cost of approximately €63 million compared to 38,000 cases avoided, 1,545 QALYs gained at a total cost of approximately €68 million in the population ≥ 70 YOA. This would result in an ICER of approximately €37,000 and €44,000/QALY, for the age cohort ≥ 60 and ≥ 70 YOA, respectively. Scenario analyses demonstrated that vaccinating at age 60 or 65 YOA would show greater public health impact and would result in the lowest observed ICER compared to vaccinating at 70 YOA. In conclusion, starting vaccination with RZV in the German population ≥ 60 YOA would demonstrate the best value from a public health and economic standpoint.

Patient preferences for dry powder inhaler attributes in asthma and chronic obstructive pulmonary disease in France: a discrete choice experiment.

BACKGROUND: Dry powder inhalers (DPIs) are often used in asthma and chronic obstructive pulmonary disease (COPD) therapies. Using the discrete choice experiment (DCE) methodology, this study conducted in France was designed to assess patients' preferences for different attributes of DPIs. METHODS: Attributes of DPIs were defined based on a literature review, patient focus group discussions and interviews with healthcare professionals (qualitative phase of the study). An online survey was then conducted among French patients with asthma or COPD to elicit patient preferences and willingness to pay (WTP) for these attributes using the DCE methodology (quantitative phase). A fractional factorial design including three blocks of 12 choice sets was created. Each choice set comprised three alternatives: two fictitious inhalers and the patient's current inhaler. Marginal utilities were estimated using a ranked ordered logit model. Interactions between attributes and disease (asthma or COPD) were tested. RESULTS: Six DPI attributes were defined based on the qualitative phase: ease of use/fool-proof priming; accurate and easy-to-read dose counter; dose confirmation; hygiene of the mouthpiece; flexibility of the device handling; ability to use the inhaler with breathing difficulties. Overall, 201 patients with asthma and 93 with COPD were included in the online survey. Patients with asthma placed most value on an inhaler that requires one step for dose preparation (WTP €4.83 [95% CI: €3.77-€5.90], relative to an inhaler requiring four steps) and one that could be used during episodes of breathing difficulties (WTP €4.49 [95% CI: €2.95-€6.02]). Patients with COPD placed most value on an inhaler that could be used during episodes of breathing difficulties (WTP €7.70 [95% CI: €5.65-€9.76]) and on the accuracy of the dose counter (WTP €5.87 [95% CI: €3.98-€ 7.77]). CONCLUSION: This study suggests that asthma and COPD patients would be willing to change their inhaler if they were offered the option of a new inhaler with improved characteristics and they place a high value on an inhaler with ease of use during breathing difficulty episodes.

Cost-Effectiveness of Mirabegron Compared with Antimuscarinic Agents for the Treatment of Adults with Overactive Bladder in the United Kingdom.

BACKGROUND: Mirabegron, a first-in-class selective oral ß3-adrenoceptor agonist, has similar efficacy to most antimuscarinic agents and a lower incidence of dry mouth in patients with overactive bladder (OAB). OBJECTIVES: To evaluate the cost-effectiveness of mirabegron 50 mg compared with oral antimuscarinic agents in adults with OAB from a UK National Health Service perspective. METHODS: A Markov model including health states for symptom severity, treatment status, and adverse events was developed. Cycle length was 1 month, and the time horizon was 5 years. Antimuscarinic comparators were tolterodine extended release, solifenacin, fesoterodine, oxybutynin extended release and immediate release (IR), darifenacin, and trospium chloride modified release. Transition probabilities for symptom severity levels and adverse events were estimated from a mirabegron trial and a mixed treatment comparison. Estimates for other inputs were obtained from published literature or expert opinion. Quality-adjusted life-years (QALYs) and total health care costs, including costs of drug acquisition, physician visits, incontinence pad use, and botox injections, were modeled. Deterministic and probabilistic sensitivity analyses were performed. RESULTS: Base-case incremental cost-effectiveness ratios ranged from £367 (vs. solifenacin 10 mg) to £15,593 (vs. oxybutynin IR 10 mg) per QALY gained. Probabilistic sensitivity analyses showed that at a willingness-to-pay threshold of £20,000/QALY gained, the probability of mirabegron 50 mg being cost-effective ranged from 70.2% versus oxybutynin IR 10 mg to 97.8% versus darifenacin 15 mg. A limitation of our analysis is the uncertainty due to the lack of direct comparisons of mirabegron with other agents; a mixed treatment comparison using rigorous methodology provided the data for the analysis, but the studies involved showed heterogeneity. CONCLUSIONS: Mirabegron 50 mg appears to be cost-effective compared with standard oral antimuscarinic agents for the treatment of adults with OAB from a UK National Health Service perspective.

Comparative efficacy and safety of medical treatments for the management of overactive bladder: a systematic literature review and mixed treatment comparison.

CONTEXT: Overactive bladder (OAB) treatment guidelines recommend antimuscarinics as first-line pharmacologic therapy. Mirabegron is a first-in-class ß3-adrenoceptor agonist licensed for the treatment of OAB and has shown to be well tolerated and effective in the treatment of OAB symptoms. OBJECTIVE: To assess the relative efficacy and tolerability of OAB medications, specifically mirabegron 50 mg versus antimuscarinics in patients with OAB. EVIDENCE ACQUISITION: A systematic literature search was performed on published peer-reviewed articles from 2000 to 2013. This review included randomised controlled trials (RCTs) studying changes in symptoms (micturition frequency, incontinence, and urgency urinary incontinence [UUI] episodes) and incidence of the most frequently reported adverse events (dry mouth, constipation) associated with current OAB medications. The following drugs were considered in addition to mirabegron: darifenacin, tolterodine immediate release (IR) and extended release (ER), oxybutynin IR/ER, trospium, solifenacin, and fesoterodine. Bayesian mixed treatment comparisons (MTCs) were performed for efficacy (micturition, incontinence, UUI) and tolerability (dry mouth, constipation, blurred vision). EVIDENCE SYNTHESIS: Overall, 44 RCTs involving 27,309 patients were included. The MTCs showed that mirabegron 50 mg was as efficacious as antimuscarinics in reducing the frequency of micturition incontinence and UUI episodes, with the exception of solifenacin 10 mg that was more efficacious than mirabegron 50 mg in improving micturition frequency and frequency of UUI. Mirabegron 50 mg had an incidence of dry mouth similar to placebo and significantly lower than all included antimuscarinics. CONCLUSIONS: Mirabegron 50 mg had similar efficacy to most antimuscarinics and lower incidence of dry mouth, the most common adverse event reported with antimuscarinics and one of the main causes of discontinuation of treatment. Despite being a powerful tool for evidence-based health care evaluation, the Bayesian MTC method has limitations. Further head-to-head comparisons between mirabegron and antimuscarinics should be conducted to confirm our results.