Objectives Previous network meta-analysis (NMA) demonstrated advantageous or similar efficacy of baloxavir marboxil (baloxavir) over neuraminidase inhibitors in otherwise healthy (OwH) influenza patients. This analysis assessed the efficacy and safety of baloxavir in the subgroup of high-risk (HR) patients and in the population of uncomplicated influenza consisting of OwH and HR patients with influenza. Methods A systematic literature review (SLR) was performed in Medline, Embase, CENTRAL and ICHUSHI up to August 8th, 2018. A Bayesian NMA was conducted to compare baloxavir with oseltamivir, zanamivir, laninamivir and peramivir in HR patients and all uncomplicated patients. Results Based on the SLR, a total of 32 studies were identified as pertinent for the analysis, including 7 studies on HR patients, 13 trials on OwH patients and 14 studies on OwH?+?HR population. NMA of 10 trials assessing HR patients demonstrated comparable time to alleviation of symptoms for all treatments. Mean decline in virus titer from baseline at 24h after treatment was significantly greater for baloxavir compared with oseltamivir and peramivir. The risks of total complications and drug-related adverse events were comparable between baloxavir and zanamivir, oseltamivir and laninamivir. These findings were highly consistent with results of the NMA using pooled evidence on the uncomplicated population of OwH and HR patients. Conclusions Baloxavir was significantly more effective than placebo regarding all outcomes except for the risk of pneumonia. Besides, baloxavir was associated with similar clinical efficacy and safety, and superior antiviral activity compared to other antivirals in HR patients, as well as in the entire population of uncomplicated patients with influenza.

OBJECTIVE: The objective was to assess the real-world cost-effectiveness of rivaroxaban, versus vitamin K antagonists (VKAs), for stroke prevention in patients with atrial fibrillation (AF) from a French national health insurance perspective. METHODS: A Markov model was developed with a lifetime horizon and cycle length of 3 months. All inputs were drawn from real-world evidence (RWE) studies: data on baseline patient characteristics at model entry were obtained from a French RWE study, clinical event rates as well as persistence rates for the VKA treatment arm were estimated from a variety of RWE studies, and a meta-analysis provided comparative effectiveness for rivaroxaban compared to VKA. Model outcomes included costs (drug costs, clinical event costs, and VKA monitoring costs), quality-adjusted life-years (QALY) and life-years (LY) gained, incremental cost per QALY, and incremental cost per LY. Sensitivity analyses were performed to test the robustness of the model and to better understand the results drivers. RESULTS: In the base-case analysis, the incremental total cost was euro714 and the total incremental QALYs and LYs were 0.12 and 0.16, respectively. The resulting incremental cost/QALY and incremental cost/LY were euro6,006 and euro4,586, respectively. The results were more sensitive to the inclusion of treatment-specific utility decrements and clinical event rates. CONCLUSIONS: Although there is no official willingness-to-pay threshold in France, these results suggest that rivaroxaban is likely to be cost-effective compared to VKA in French patients with AF from a national insurance perspective.

ABSTRACT Objective: To provide recommendations for addressing previously identified key challenges in health economic evaluations of Gene Replacement Therapies (GRTs), including: 1) the assessment of clinical effectiveness; 2) the valuation of health outcomes; 3) the time horizon and extrapolation of effects beyond trial duration; 4) the estimation of costs; 5) the selection of appropriate discount rates; 6) the incorporation of broader elements of value; and 7) affordability. Methods: A literature review on economic evaluations of GRT was performed. Interviews were conducted with 8 European and US health economic experts with experience in evaluations of GRT. Targeted literature reviews were conducted to investigate further potential solutions to specific challenges. Recommendations: Experts agreed on factors to be considered to ensure the acceptability of historical cohorts by HTA bodies. Existing prospective registries or, if not available, retrospective registries, may be used to analyse different disease trajectories and inform extrapolations. The importance of expert opinion due to limited data was acknowledged. Expert opinion should be obtained using structured elicitation techniques. Broader elements of value, beyond health gains directly related to treatment, can be considered through the application of a factor to inflate the quality-adjusted life years (QALYs) or a higher cost-effectiveness threshold. Additionally, the use of cost-benefit analysis and saved young life equivalents (SAVE) were proposed as alternatives to QALYs for the valuations of outcomes of GRT as they can incorporate broader elements of value and avoid problems of eliciting utilities for paediatric diseases. Conclusions: While some of the limitations of economic evaluations of GRT are inherent to limited clinical data and lack of experience with these treatments, others may be addressed by methodological research to be conducted by health economists.

ABSTRACT Background Ischaemic stroke (IS) is a major cause of death and disability and affects the quality of life of patients. Previous studies focused on urban populations. Objective To evaluate the health-related quality of life (QoL) of patients with history of IS and living in a rural area in Poland. Patients Rural population of 172 patients discharged from a district hospital in Zakopane, Poland with a diagnosis of IS in the period from 01.01.2005 to 31.10.2006. Intervention QoL was evaluated using the European Quality of Life Scale-5 Dimensions EQ-5D-3 L (EQ-5D) and the Short Form Health Survey ? 12 version 2 (SF-12). Results In the EQ-5D survey, 57.3% of patients had only some problems with mobility, 40.3% with usual activities, 63.2% with pain/discomfort, 59% with anxiety/depression, and 32.2% with self-care. In the SF-12 survey, both summary components (physical and psychological) were reduced compared to the population norm. Conclusion The quality of life in IS survivors is clearly reduced in the majority of domains assessed by the EQ-5D and SF-12 questionnaires. The most important factors affecting QoL were the functional state, depression and anxiety. A significant difference as compared to to urban and mixed populations was observed for a reduced SF-12 mental health component and for the EQ-5D visual analogue scale. We found no effect of gender, age or cognitive disorders on the outcomes of SF-12.

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.

Objectives: While several authors have suggested using a multi-criteria approach for orphan drug assessment and proposed lists of determinants of orphan drug value, studies on social preferences regarding these determinants remain limited. The current study aimed to identify preferences of the French general population regarding attributes characterizing the value of orphan drugs in a discrete choice experiment.Methods: The list of attributes was formed based on a literature search and was refined through expert interviews, a focus group, and a pilot study. The final list included nine attributes: disease-associated disability, disease-associated mortality, number of patients, availability of alternative treatments, treatment impact on disease disability, treatment impact on mortality, treatment safety, uncertainty around therapeutic effect, and annual treatment cost per patient. Members of the General Public were presented with 12 choice sets containing two drug profiles described according to the attributes and an option to fund neither of these treatments. The questionnaire was disseminated online. A conditional logit model with random effects was used to estimate the weight of each attribute.Results: A total of 958 persons participated in the study (48.7% male, mean age: 47.5 years). All attributes except for disease-associated disability had a statistically significant influence on the choices made by participants. The attribute with the highest weight was treatment impact on mortality (p < 0.0001), followed by uncertainty around therapeutic effect (p < 0.0001). The direction of results was generally consistent with intuition: patients preferred a drug with a larger impact on mortality, a larger impact on disability, with mild or no adverse events, with less uncertainty. Although patients appeared to prefer drugs with a lower budget impact, the relationship between patient preferences and costs was more complex.Conclusions: Preferences of the general public between orphan drugs are mostly driven by the impact on mortality and the degree of certainty regarding the available evidence.

Health state utility values (HSUVs) identified from utility elicitation studies are widely used in pharmacoeconomic evaluations for chronic hepatitis C (CHC) and are particularly instrumental in health technology assessment (HTA) evaluations such as those from the National Institute for Health and Care Excellence (NICE).

BACKGROUND: In recent years there is a growing interest in public beliefs about mental disorders. Numerous representative population-based studies have been conducted around the globe, also in European countries bordering on the Mediterranean Sea. However, relatively little is known about public beliefs in countries in Northern Africa. OBJECTIVE: To fill this gap by comparing public beliefs about mental disorders in Tunisia and Germany, focusing on causal beliefs, help-seeking recommendations and treatment preferences. METHODS: Representative national population-based surveys have been conducted in Tunisia in 2012 (N = 811) and in Germany in 2011 (N = 1852), using the same interview mode and the same fully structured interview starting with a vignette depicting a person suffering from either schizophrenia or depression. RESULTS: In Tunisia, the public was more likely to adopt psychosocial and to reject biogenetic explanations than in Germany. Correspondingly, psychological treatments were more frequently recommended and biological ones more frequently advised against. There was also a strong inclination to share religious beliefs and to recommend seeking religious advice. Tunisians tended much more than Germans to hold moralistic views and to blame the afflicted person for his or her illness. In Tunisia, the public tended less to differentiate between schizophrenia and depression than in Germany. CONCLUSION: Marked differences between Tunisia and Germany exist in public beliefs about the causes of mental disorders and their treatment, which correspond to differences in cultural orientations prevailing in these countries. Mental health professionals need to be sensitive to the particular cultural context in which they operate, in order to be able to reach those they intend to care for.

Real-world evidence (RWE) provides external validity, supplementing and enhancing the randomized controlled trial (RCT) data with valuable information on patient behaviours and outcomes, turning efficacy and safety results into real-world effectiveness and risks, but the use of RWE is associated with challenges.The objectives of this communication were to (1) summarise all guidance on how to conduct an RWE meta-analysis (MA) and how to develop an RWE cost-effectiveness model, (2) to describe our experience, challenges faced and solutions identified, (3) to provide recommendations on how to conduct such analyses.No formal guidelines on how to conduct an RWE MA or to develop an RWE cost-effectiveness model were identified. Using the context of non-vitamin K antagonist oral anticoagulants (NOACs) in stroke prevention in atrial fibrillation, we conducted an RWE MA, after having identified sources of uncertainty. We then implemented the results in an RWE cost-effectiveness model, defined as a model where all inputs come from RWE, including all parameters related to treatment effect. Based on challenges faced, our first recommendation relates to the necessity of conducting sensitivity analyses, either based on clinical or methodological considerations. Our second recommendation is the need for extensive collaboration with a wide range of experts, during the development of the analyses protocols, the implementation of the analyses and the interpretation of the results.RWE may address a number of gaps related to the treatment effect, and RWE economic evaluations for the treatment effect can provide extremely valuable insights into real-world economic value of interventions. As the increased recognition of the value of RWE could influence health technology assessment decision, and current practices, this communication supports the urgent need of more formal guidelines.