Background The quality of biologicals, including biosimilars, is subject to change as a result of manufacturing process modifications following initial authorization. It is important that such product changes have no adverse impact on product efficacy or safety, including immunogenicity. Objectives The aim of this study was to investigate the number and types of manufacturing changes for originator mAbs (the reference for the comparability exercise to confirm biosimilarity) according to European Public Assessment Report (EPAR) documentation and to ascertain the level of risk these changes might impart. The extensive body of evidence contained in the EPAR documents can help support the EMA during the EC marketing authorization approval process for biosimilars, since it provides a broad base of scientific experience. Research designs and methods For EPAR-listed mAbs, details of all changes listed chronologically in the EPAR were evaluated and described. Based on these descriptions the manufacturing changes can be categorized by risk status (low, moderate or high). Results Entries for 29 mAbs with publicly available EPAR reports were reviewed. These contained details of 404 manufacturing changes authorized by the European Medicines Agency (EMA): 22 were categorized as high risk, 286 as moderate risk and 96 as low risk manufacturing changes. A limitation of this analysis is that it only summarizes publicly available data from EPAR documents. Conclusions Manufacturing change data indicate that the EMA has significant experience of process changes for originator mAbs, and the impact they may have on the efficacy and safety of biologicals. This experience will be useful in biosimilar product development to ensure adherence to sound scientific principles. Compared with the established manufacturing process for a reference product, the production of biosimilars will usually be different. Consequently, in addition to a comprehensive comparative functional and physicochemical characterization analysis, clinical data is required to confirm mAb biosimilarity.

Background We adapted the eHealth Literacy Scale (eHEALS) for Hungary and tested its psychometric properties on a large representative online sample of the general population. Methods The Hungarian version of eHEALS was developed using forward–backward translation. For the valuation study, 1000 respondents were recruited in early 2019 from a large online panel by a survey company. We tested internal consistency, test–retest reliability and construct and criterion validity using classical test theory, as well as item characteristics using an item-response theory (IRT) graded response model (GRM). Results 55% of respondents were female, and 22.1% were ≥ 65 years old. Mean eHEALS score was 29.2 (SD: 5.18). Internal consistency was good (Cronbach’s α = 0.90), and test–retest reliability was moderate (intraclass correlation r = 0.64). We identified a single-factor structure by exploratory factor analysis, explaining 85% of test variance. Essential criteria for GRM analysis were met. Items 3 and 4 (search of health resources) were the least difficult, followed by items 5 and 8 (utilisation of health information), and then items 1 and 2 (awareness of health resources). Items 6 and 7 (appraisal of health resources) were most difficult. The measurement properties of eHEALS were not affected by gender, age, education or income levels. Female gender, older age, intensity of health information seeking, formal health education and visit at the electronic health-record website were associated with higher eHEALS scores, as well as best and worst self-perceived health states, BMI < 25 and participation at health screenings over the past year. Conclusions The Hungarian eHEALS is a useful and valid tool for measuring subjective eHealth literacy. Electronic supplementary material The online version of this article (10.1007/s10198-019-01062-1) contains supplementary material, which is available to authorized users.

Background We aimed to investigate the burden of informal care in Hungary (HU), Poland (PL) and Slovenia (SI). Methods A cross-sectional online survey was performed involving representative samples of 1000 respondents per country. Caregiving situations were explored; health status of informal caregivers/care recipients and care-related quality of life were assessed using the EQ-5D-5L and CarerQol-7D. Results The proportion of caregivers was (HU/PL/SI) 14.9, 15.0 and 9.6%, respectively. Their mean age was 56.1, 45.6 and 48.0, and the average time spent on informal care was 27.6, 35.5 and 28.8 h/week. Chronic care was dominant (> 1 year: 78.5%, 72.0%, 74.0%) and care recipients were mainly (own/in-law) parents. Average EQ-5D-5L scores of care recipients were 0.53, 0.49 and 0.52. For Poland and Slovenia, EQ-5D-5L scores of informal care providers were significantly lower than of other respondents. Average CarerQol-7D scores were (HU/PL/SI) 76.0, 69.6 and 70.9, and CarerQol-VAS was 6.8, 6.4 and 6.6, respectively. Overall, 89, 87, and 84% of caregivers felt some or a lot fulfilment related to caring. Problems with combining tasks with daily activities were most important in Hungary and Slovenia. Women had a higher probability of being a caregiver in Hungary. CarerQol-7D scores were significantly associated with caregivers' EQ-5D-5L scores. In Hungary and Poland, living in a larger household was positively, while caring for patients with mental health problems was negatively associated with CarerQol-7D scores. Conclusions These first results from the Central and Eastern European region using preference-based measures for the evaluation of informal care can serve as a valuable input for health economic analyses.

Background: The neutrophil-to-lymphocyte ratio (NLR) and the platelet-to-lymphocyte ratio (PLR) may be useful for drawing conclusions about the survival of head and neck squamous cell carcinoma (HNSCC) patients. Methods: Clinical data of 156 patients managed for HNSCC at two head and neck surgery centres were analyzed retrospectively. We studied the relationships between survival and PLR as well as NLR. Results: With regards to 5-year survival, the difference between the two groups with PLR values lower or higher than the threshold was statistically significant (p = 0.004), and we found the same for disease-free survival (p = 0.05), and tumour-specific mortality (p = 0.009). Concerning NLR, the difference in tumour-specific survival was statistically significant (p = 0.006). According to the multivariate analysis, NLR values higher than the threshold indicated an enhanced risk for overall as well as for tumour-specific mortality. Conclusion: In HNSCC patients, a high NLR may be considered as an independent risk factor for 5-year overall survival.Malignant tumours influence the number of platelets and alter their functioning. However, the mechanisms of the relationship between thrombocytosis and the tumour have not yet been fully elucidated and several hypotheses have been proposed [2].The facilitatory role of chronic inflammation in the development and progression of solid tumours have been described for malignancies of the lung, breast, and gastrointestinal tract, the prostate, and the ovaries [3-7], as well as for HNSCC [8,9].Neutrophils might, in fact, facilitate tumour growth and the formation of metastases-these cells can inhibit the activities of the lymphocytes and thereby attenuate the antitumour immune response [10]. Neutrophil cells can contribute to carcinogenesis and tumour progression in many ways [11]: (1) These cells can release genotoxic substances, which damage the DNA of epithelial cells [12]. (2) They can promote tumour growth by releasing soluble factors and proteases, such as prostaglandin E2 and neutrophil elastase [13,14]. (3) Neutrophils facilitate metastasis formation by enhancing the capabilities of the tumour cells for migration, invasive spread, and colony formation, as well as by breaking down the extracellular matrix [15]. (4) They contribute to the formation of new blood vessels by producing pro-angiogenic factors, such as matrix metalloproteinase-9, and vascular endothelial growth factor [16]. (5) Neutrophils exert immunosuppressive action by inhibiting effector T-cells along with the proliferation and the functioning of natural killer cells, as well the fact that they enhance tumour growth and metastasis formation through the modulation of macrophage activity [17].These observations suggest that neutrophil-to-lymphocyte ratio (NLR), and platelet-to-lymphocyte ratio (PLR) determined in the blood of patients with a malignancy might be related to tumour growth [18].Our study intended to ascertain whether pre-treatment NLR and PLR values determined in HNSCC patients are suitable predi...

Purpose We aimed to develop and assess the psychometric characteristics of the Hungarian language version of two well-being capability measures, the ICEpop CAPability measure for Adults/Older people (ICECAP-A/-O), and to establish population norms. Methods A cross-sectional survey was performed involving a representative sample of the Hungarian population. Socio-demographic characteristics, the use and provision of informal care were recorded. The Minimum European Health Module (MEHM), EQ-5D-5L, WHO-5 well-being index, happiness and life satisfaction visual analogue scale (VAS), Satisfaction with Life Scale (SWLS) measures were applied alongside the ICECAP-A (age-group 18–64) and ICECAP-O (age-group 65+). Results Altogether 1568 and 453 individuals completed the ICECAP-A/-O questionnaires, respectively. Cronbach’s alpha was 0.86 for both measures (internal consistency). Subgroup analyses showed positive associations between ICECAP-A/-O scores and marital status, employment, income, health status (MEHM) and informal care use (construct validity). Pearson correlations were strong (r > 0.5; p < 0.01) between ICECAP-A/-O indexes and EQ-5D-5L, WHO-5, happiness and satisfaction VAS and SWLS scores (convergent validity). The age, education, and marital status were no longer significant in the multiple regression analysis. Test–retest average (SD) scores were 0.88 (0.11) and 0.89 (0.10) for the ICECAP-A, and equally 0.86 (0.09) for the ICECAP-O (reliability). Conclusion This is the first study to provide ICECAP-A/-O population norms. Also, it is the first to explore associations with WHO-5 well-being index which, alongside the MEHM measures, enable estimates from routinely collected international health statistics. The Hungarian ICECAP-A/-O proved to be valid and reliable measurement tools. Socio-demographic characteristics had minor or no impact on ICECAP-A/-O. Other influencing factors deserve further investigation in future research.

Introduction: Early biological treatment of rheumatoid arthritis (RA) may reverse the autoimmune response in some patients resulting in favorable long-term outcomes. Although the cost-effectiveness of this strategy has been questioned, biosimilar entries warrant the revision of clinical and pharmaco-economic evidence. Areas covered: We conducted a systematic review of randomized controlled trials (RCTs) published up to 24 May 2018 in Pubmed, EMBASE and Cochrane CENTRAL, comparing infliximab with non-biological therapy in patients with RA naïve to methotrexate. We performed meta-analyses for efficacy outcomes at month 6 and years 1 and 2. Six RCTs were identified, involving 1832 patients. At month 6 ACR70 response and remission, and at year 1 ACR20/ACR70 responses and remission were improved significantly with first-line infliximab versus control. The differences were not significant at year 2. We reviewed cost-utility studies, up to 31 October 2018 in PubMed, Cochrane CENTRAL and the CRD HTA databases. Four studies indicated that first-line use of originator infliximab calculated at 2005-2008 prices was not cost-effective. Expert opinion: We demonstrated the efficacy benefits of first-line infliximab therapy up to 1 year in methotrexate-naïve RA. We highlighted the need for standardized reporting of outcomes and conducting cost-effectiveness analyses of first-line biosimilar therapy in RA.

Background In the Central and Eastern European region, the British EQ-5D-3L value set is used commonly in quality of life (QoL) studies. Only Poland and Slovenia have country-specific weights. Our study aimed to investigate the impact of value set choice on the evaluation of 18 chronic conditions in Hungary. Methods Patients’ EQ-5D-3L index scores were calculated using the VAS-based Slovenian and European and the time-trade-off-based Polish and British value sets. We performed pairwise comparisons of mean index values by dimensions, diagnoses and age groups. We evaluated disease burden by comparing index values matched by age and gender in each condition with those of the general population of the CEE region in all four value sets. Results Altogether, 2421 patients (55% female) were included in our sample with the average age of 55.87 years (SD = 17.75). The average Slovenian, European, Polish and British EQ-5D-3L scores were 0.598 (SD = 0.279), 0.661 (SD = 0.257), 0.770 (SD = 0.261) and 0.644 (SD = 0.279), respectively. We found highly significant differences in most diagnoses, with the greatest difference between the Polish and Slovenian index values in Parkinson’s disease (0.265). Systematic pairwise comparison across all conditions and value sets revealed greatest differences between the time-trade-off (TTO) and VAS-based value sets as well as varying sensitivity of the disease burden evaluations of chronic disease conditions to the choice of value sets. Conclusions Our results suggest that the choice of value set largely influences the health state utility results in chronic diseases, and might have a significant impact on health policy decisions.

Background During the COVID-19 pandemic, contact tracing apps have received a lot of public attention. The ongoing debate highlights the challenges of the adoption of data-driven innovation. We reflect on how to ensure an appropriate level of protection of individual data and how to maximize public health benefits that can be derived from the collected data. Objective The aim of the study was to analyze available COVID-19 contact tracing apps and verify to what extent public health interests and data privacy standards can be fulfilled simultaneously in the process of the adoption of digital health technologies. Methods A systematic review of PubMed and MEDLINE databases, as well as grey literature, was performed to identify available contact tracing apps. Two checklists were developed to evaluate (1) the apps’ compliance with data privacy standards and (2) their fulfillment of public health interests. Based on both checklists, a scorecard with a selected set of minimum requirements was created with the goal of estimating whether the balance between the objective of data privacy and public health interests can be achieved in order to ensure the broad adoption of digital technologies. Results Overall, 21 contact tracing apps were reviewed. In total, 11 criteria were defined to assess the usefulness of each digital technology for public health interests. The most frequently installed features related to contact alerting and governmental accountability. The least frequently installed feature was the availability of a system of medical or organizational support. Only 1 app out of 21 (5%) provided a threshold for the population coverage needed for the digital solution to be effective. In total, 12 criteria were used to assess the compliance of contact tracing apps with data privacy regulations. Explicit user consent, voluntary use, and anonymization techniques were among the most frequently fulfilled criteria. The least often implemented criteria were provisions of information about personal data breaches and data gathered from children. The balance between standards of data protection and public health benefits was achieved best by the COVIDSafe app and worst by the Alipay Health Code app. Conclusions Contact tracing apps with high levels of compliance with standards of data privacy tend to fulfill public health interests to a limited extent. Simultaneously, digital technologies with a lower level of data privacy protection allow for the collection of more data. Overall, this review shows that a consistent number of apps appear to comply with standards of data privacy, while their usefulness from a public health perspective can still be maximized.