Association of exogenous factors with the access to innovative pharmaceutical products in Hungary.

INTRODUCTION: Access to innovative pharmaceuticals is thought to be associated with several exogenous factors related to the local legal or financial framework of pharmaceutical reimbursement. Our aim was to describe the association between the outcome of the reimbursement procedure on innovative pharmaceutical submissions in Hungary and several potential explanatory variables related to the legal or financial framework of reimbursement procedures, such as the submission implying a need for a legal act to conclude on a positive decision; having a risk-sharing agreement (RSA) in place at the time of submission; the aim of the submission and expenditure on individual funding requests. METHODS: Publicly available administrative announcements of the Hungarian National Health Insurance Fund Manager were used to construct the analysis dataset including all concluded procedures between 1 January 2018 and 7 June 2021, complemented with information on the overall aim of the submission (new compound or new indication). Logistic regression models were used to estimate odds ratios while adjusting for potential confounding. RESULTS: Needing a legislative change as a proxy of involving high-level decision makers to reimburse had a lower (OR = 0.05, CI95%:0.02-0.11), whereas having an RSA had a statistically significant higher chance of a positive decision (OR = 3.49, CI95%:1.56-7.82). In contrast, neither the overall purpose of the submission (OR = 1.32, CI95%:0.65-2.69), nor the average biennial expenditure on individual funding requests exceeding 200 million HUFs (OR = 1.04, CI95%:0.92-1.19) had a statistically significant association with the decision. CONCLUSIONS: This study quantitatively demonstrated that the need for legal acts to conclude on a positive decision decreases, whereas having an RSA for the particular product increases the likelihood of a positive reimbursement decision in Hungary. The role of other factors remain unclear. Our findings suggest that the legal requirements and RSAs play key roles in the reimbursement of innovative pharmaceuticals and can be viewed as potential areas of policy interventions in expanding access to these products, although the feasibility of such interventions need strong commitment from decision-makers, as well as implying increased autonomy to the entities involved in reimbursement procedures. Further research is needed to assess the impact of endogenous and exogenous factors in a coherent framework.

Development, testing, and implementation of a new procedure to assess the clinical added benefit of pharmaceuticals.

OBJECTIVES: The reimbursement process for innovative health technologies in Hungary lacks any formalized assessment of clinical added benefit (CAB). The aim of this research is to present the development, retrospective testing, and implementation of a local assessment framework for determining the CAB of cancer treatments at the Department of Health Technology Assessment of the National Institute of Pharmacy and Nutrition in Hungary. METHODS: The assessment framework was drafted after screening existing methods and a retrospective comparison of local reimbursement dossiers to that of German and French methods. The Magnitude of Clinical Benefit Scale of the European Society for Medical Oncology was chosen to rate the extent of CAB in oncology, as part of a conclusion complemented by the assessment of endpoint relevance and the quality of evidence. Several rounds of retrospective assessments have been conducted involving all clinical assessors, iterated with semistructured discussions to consolidate divergence between assessors. External stakeholders were consulted to provide feedback on the framework. RESULTS: Retrospective assessments resulted in average more than 75 percent concordance between assessors on each element of the conclusion. Input from ten stakeholders was also incorporated; stakeholders were generally supportive, and they mostly commented on the concept, the elements of the framework, and its implementation. CONCLUSIONS: The procedure is suitable for routine use in the decision-making process to describe the CAB of antineoplastic technologies in Hungary. Further extension of the framework is required to cover more disease areas for structured and comparable conclusions on CAB of innovative health technologies.

A critical assessment framework to identify, quantify and interpret the sources of uncertainty in cost-effectiveness analyses.

BACKGROUND: Using a standardized approach to describe the sources of uncertainty in cost-effectiveness analyses might bring added value to the local critical assessment procedure of reimbursement submissions in Hungary. The aim of this research is to present a procedural framework to identify, quantify and interpret sources of uncertainty, using the reimbursement dossier of darolutamide as an illustrative example. METHODS: In the procedural framework designed for the critical assessment of cost-effectiveness analyses, the quantifiability of an identified source of uncertainty is assessed through the input parameters of the originally submitted model, which is followed by the interpretation of its impact on estimates of costs and outcomes compared to the base case cost-effectiveness conclusion. RESULTS: Based on our experiences with the recent reimbursement dossier of darolutamide, the significant and quantifiable sources of uncertainty were the time horizon of the economic analysis; the restriction of the efficacy analysis population; long-term relative effectiveness of darolutamide; price discount on subsequent therapies. We identified resource use patterns for comparator and subsequent therapies as a quantifiable, yet non-significant source of uncertainty. The EQ-5D value set used to estimate utility values was identified as a non-quantifiable and potentially not significant source of uncertainty. CONCLUSIONS: The procedural framework, demonstrated with an example, was sufficiently flexible and coherent to document and structure the sources of uncertainty in cost-effectiveness analyses. The full-scale use of this framework is desirable during the decision-making process for reimbursement in Hungary. The further formalization of identifying sources of uncertainty is a possible subject of methodological development.

Oral Health Status of Physically Disabled Inpatients - Results from a Hungarian Single-Centre Cross-Sectional Study.

PURPOSE: The aim of this study was to assess the aetiological factors having an impact on the prevalence of dental caries, missing or filled teeth in a subsample of a single-centre cross-sectional study conducted among the inpatients of the National Institute of Medical Rehabilitation in Hungary. MATERIALS AND METHODS: Data collection was carried out through the full mouth screening for dental caries according to World Health Organization (WHO) criteria and a questionnaire covering social background, oral hygiene routine, eating habits for all inpatients who underwent rehabilitation between May 2019 and March 2020. RESULTS: The mean + standard deviation (SD) DMF-T score in the study sample of 110 physically disabled patients was 18.90 + 7.85. Factors which influenced DMF-T were age, frequency of dental visits and frequency of toothbrushing. The caries prevalence was higher than in the general Hungarian non-disabled population. CONCLUSION: In the current study it was apparent that patients with physical disability had less favourable oral health with frequent occurrence of dental caries and missing teeth. Based on the results of the current study, new, targeted prevention and intervention can be developed.

[Relative frequency of urinary tract infections in patients affected by diabetes mellitus type 2 treated with metformin and SGLT2 inhibitor. Network meta-analysis]. / A húgyúti fertozések relatív gyakorisága metforminnal és SGLT2-gátlóval kezelt 2-es típusú diabetes mellitusban szenvedo betegekben. Hálózati metaanalízis.

Introduction and aim: The of this research was to conduct a network meta-analysis based on a systematic literature search to compare the relative frequency of urinary tract infections using sodium-glucose cotransporter-2 (SGLT2) inhibitors combined with metformin in the therapy of type 2 diabetes. Method: MEDLINE and EMBASE databases were searched to identify publications of randomized, controlled trials investigating SGLT2 inhibitors combined with metformin in the therapy of type 2 diabetes and providing information on the frequency of urinary tract infections. Results: 10 165 unique citations were screened to identify 10 publications to be included in the network meta-analysis. The network meta-analysis showed reduced risk of urinary tract infections for low-dose ertugliflozin compared to other SGLT2 inhibitors (ertugliflozin 5 mg vs. empagliflozin 10 mg: RR: 0.606, 95% CrI: 0.264-1.415; ertugliflozin 5 mg vs. dapagliflozin 10 mg: RR = 0.853, 95% CrI: 0.301-2.285). For high-dose comparisons, empagliflozin 25 mg showed reduced risk of urinary tract infections compared to both ertugliflozin 15 mg (RR = 0.745, 95% CrI 0.330-1.610) and dapagliflozin 10 mg (RR = 0.680, 95% CrI: 0.337-1.289). The difference between active substances and their doses was not statistically significant for the relative frequency of urinary tract infections. The meta-regression revealed a statistically significant association between baseline fasting plasma glucose level and relative frequency of urinary tract infections (ß = 0.785, 95% CrI: 0.062-1.587). Conclusion: There was no statistically significant difference between SGLT2 inhibitors investigated in this study in terms of the relative frequency of urinary tract infections. This research demonstrates the applicability of network meta-analyses when assessing the relative effectiveness and safety of interventions. Orv Hetil. 2020; 161(13): 491-501.

Atmospheric fronts as minor cardiovascular risk factors, a new approach to preventive cardiology.

BACKGROUND: Cardiovascular diseases are the number one cause of death globally and represent 31% of all global deaths. The aim of our study was to determine the influence of front effects on acute cardiovascular diseases (ACVDs). METHODS: We obtained all ACVD admissions in a Central-European region, Hungary, Budapest. A time-series analysis was applied to 6499 morbidity cases during a five-year period (2009-2013). Poisson-regression model was used and adjusted for air temperature, pressure, humidity, wind velocity, their interactions and seasonality to assess the association of fronts and ACVDs. RESULTS: There is a positive significant association between ACVDs and a cold front effect lagged by one day (p=0.018) with a relative risk (RR) of 1.095 [95% CI (1.021,1.181)]. Our findings show that among patient subgroups with major cardiovascular risk factors (hypertension, diabetes, hyperlipidemia, history of CVDs) the patterns are similar, but occluded fronts also have a significant effect. CONCLUSION: Atmospheric fronts could play an important role in the pathogenesis of ACVDs. Our findings might help to provide a better understanding about fronts as minor cardiovascular risk factors and to organize medical prevention more effectively. Our research project may become a basis of a new field of preventive cardiovascular medicine in the future.

Complex effects of atmospheric parameters on acute cardiovascular diseases and major cardiovascular risk factors: data from the CardiometeorologySM study.

Several studies have examined the cardiovascular effects of atmospheric parameters as separate factors; however, few have investigated atmospheric parameters' joint effects. We aim to explore the joint effects of atmospheric parameters on acute cardiovascular diseases (ACVDs) and on major cardiovascular risk factors (CRFs). We correlated all ACVD admissions with major CRFs and local atmospheric conditions during a 5-year study period. A seasonal variation was detected in a higher incidence rate during cold atmospheric conditions. There were significant incidence relative ratios, including: 1.140 (95% CI [1.020, 1.283]) for daily temperature change (≥5 °C); 0.991 (95% CI [0.988, 0.994]) for average daily temperature; and 1.290 (95% CI [1.090, 1.599]) for the interaction of daily temperature change (≥5 °C) with humidity change (≥40%). We observed a significant association between the atmospheric parameters' joint effects and hyperlipidaemia, diabetes, and previous ACVDs. Patients with diabetes had the highest significant incidence relative ratio at 2.429 (95% CI [1.088, 5.424]) for humidity-temperature interactions. Thus, the atmospheric parameters' joint effects play an important role as minor CRFs. These unfavourable atmospheric situations are predicted to increase the number of ACVDs mainly. Our study may help to organize prevention strategies more effectively and to reduce cardiovascular risks.

Implication of external price referencing and parallel trade on pharmaceutical expenditure: indirect evidence from lower-income European countries.

External price referencing (EPR) is applied more and more frequently worldwide by payers to control pharmaceutical prices. Together with the parallel trade of pharmaceuticals, EPR may result in lower pharmaceutical prices in higher-income countries and higher prices in lower-income countries, which implies that pharmaceutical expenditure grows more rapidly in the latter than in the former group. Our objective was to assess this hypothesis. We used hierarchical linear models on country-level panel data to show that-after controlling for compounding factors such as GDP, the proportion of the old-age population or life expectancy-the annual growth rate of pharmaceutical expenditure was 2.1% points larger in the lower- than in the higher-income members of the European Union between 2000 and 2008. This difference in trends became non-significant (0.6% points) after the onset of the global economic crisis. There was no significant difference between lower- and higher-income countries in the growth rate of non-pharmaceutical health expenditure in either period. Our results indirectly support the presence of price convergence of pharmaceuticals among European countries, and EPR and parallel trade may provide a reasonable explanation to the observed trend difference of pharmaceutical expenditure in the two groups of countries between 2000 and 2008. This higher growth rate of pharmaceutical expenditure put extra burden on public health care budgets in lower-income countries and resulted in disproportionately more cost-containment measures compared to higher-income countries after 2008. It remains to be seen whether the disappearance of the difference in trend growth rates due to special health policy interventions in countries with economic difficulties is temporary or permanent.

[Changing of the patient safety culture in the pilot institutes of the Hungarian accreditation program]. / A betegbiztonságot támogató szervezeti kultúra változása a hazai akkreditációs programot tesztelo intézményekben.

INTRODUCTION: The accreditation system for health care providers was developed in Hungary aiming to increase safety, efficiency, and efficacy of care and optimise its organisational operation. AIM: The aim of this study was to assess changes of organisational culture in pilot institutes of the accreditation program. METHOD: 7 volunteer pilot institutes using an internationally validated questionnaire were included. The impact study was performed in 2 rounds: the first before the introduction of the accreditation program, and the second a year later, when the standards were already known. Data were analysed using descriptive statistics and logistic regression models. RESULTS: Statistically significant (p<0.05) positive changes were detected in hospitals in three dimensions: organisational learning - continuous improvement, communication openness, teamwork within the unit while in outpatient clinics: overall perceptions of patient safety, and patient safety within the unit. CONCLUSIONS: Organisational culture in the observed institutes needs improvement, but positive changes already point to a safer care. Orv. Hetil., 2016, 157(42), 1667-1673.

Cost-effectiveness of a risk-based secondary screening programme of type 2 diabetes.

OBJECTIVE: The objective of this study was to develop a long-term economic model for type 2 diabetes to describe the entire spectrum of the disease over a wide range of healthcare programmes. The model evaluates a public health, risk-based screening programme in a country specific setting. METHODS: The lifespan of persons and important phases of the disease and related interventions are recorded in a Markov model, which first simulates the effect of screening, then replicates important complications of diabetes, follows the progression of individuals through physiological variables and finally calculates outcomes in monetary and naturalistic units. RESULTS: The introduction of the screening programme nearly doubled the proportion of diagnosed patients at the age of 50 and prolonged life expectancy. Three-yearly screening gained 0.0229 quality adjusted life years for an additional €83 per person compared with no screening and resulted an incremental cost-effectiveness ratio of €3630/quality adjusted life years. CONCLUSION: From the economic perspective introduction of the 3-yearly screening programme is justifiable and it provides a good value for money. Copyright © 2016 John Wiley & Sons, Ltd.

The cost-effectiveness of ulipristal acetate tablets in treating patients with moderate to severe symptoms of uterine fibroids.

OBJECTIVES: Ulipristal acetate is a selective progesterone receptor modulator that has been demonstrated to be an effective 3-month pre-operative treatment for moderate to severe symptoms of uterine fibroids in adult women of reproductive age. The aim of this analysis was to assess the cost-effectiveness of 5mg ulipristal as an add-on therapy to standard pre-surgical observation and treatment in Hungary. STUDY DESIGN: A Markov model was developed using a 10-year time horizon. Ulipristal was compared with pre-surgical observation and immediate hysterectomy. The model comprised the following mutually exclusive health states: mild, moderate, severe, or persistent severe excessive bleeding disorder; myomectomy; post-myomectomy with mildly to moderately excessive bleeding disorder; post-myomectomy with severely excessive bleeding disorder; hysterectomy; post-hysterectomy; post-menopause; and death. Transition probabilities and utility values were obtained from clinical trials and the scientific literature. Resource utilisation and unit costs were derived from a consensus panel of clinical experts, National Health Insurance Fund tariffs, and publications. RESULTS: Adding a 3-month course of ulipristal to pre-operative observation was predicted to achieve an additional 0.021 quality-adjusted life years (QALYs) at an estimated incremental cost of €397, which would result in an incremental cost of €19,200/QALY. When 3 months of ulipristal therapy was compared with immediate hysterectomy, the incremental cost-effectiveness ratio was reduced to €3575/QALY. The results were most sensitive to the utility value of the post-hysterectomy health state but responsive to changes in other model parameters. CONCLUSIONS: The results of this analysis suggest that adding ulipristal treatment to standard pre-surgical therapy represents a good value for money in Hungary. The inclusion of societal benefits may considerably reduce the cost-effectiveness ratio.

[Assessment of the pharmaceutical expenditure in Hungary]. / A magyar gyógyszerkiadások nagyságának értékelése.

Scarcity of health care resources draws attention to the expenditure on pharmaceuticals, as drugs are considered to be one of the major growth drivers of health care spending. This article assesses the Hungarian expenditure on pharmaceuticals by taking into account the economic status of the country and benchmarks from other OECD countries with special focus on indicators of Visegrad V4 countries (Czech Republic, Slovakia, Poland and Hungary). Our results highlight the heterogeneity of pharmaceutical expenditure data derived from different indicators among observed countries. Pharmaceutical spending is relatively higher in middle-income countries, mainly due the price convergence of innovative drug's, on contrary manpower cost of health care services are adjusted to local price levels, therefore the price differential of health care services between middle income and developed countries is greater. International trends of the global pharmaceutical market are also valid in Hungary. Increased private funding, mainly out of pocket payments above the average of V4 countries, has been the major growth driver of pharmaceutical expenditure recently in Hungary. Increased private pharmaceutical expenditure was mainly derived from the severe cost-containment measures in 2006. The annual growth rate of the National Health Insurance Fund's pharmaceutical budget for drug reimbursement was 1.37% in real terms between 1994 and 2009. This is much beneath the expansion of global pharmaceutical market. Consequently, cost-containment of public pharmaceutical spending was very successful in the last fifteen years, and the burden of market growth has been shifted to households. Public health programmes, investment into preventive care, with consideration on unfavourable Hungarian morbidity and mortality indicators, however, necessitate the increase of public pharmaceutical budget. In order to improve the allocative efficiency of health care spending, available resources should be spent only on effective, cost-effective, economically affordable medicines.