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.

[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.

[Adherence, methodology and studies in Hungary]. / Beteg-együttmuködés, módszertani kérdések és hazai vizsgálatok.

Adherence to therapies is a primary determinant of treatment success. Poor adherence has a negative impact on clinical benefits and therefore reduces the overall effectiveness of health care systems. Numerous methods have been used in attempts to adequately assess patient adherence. The choice of a method for measuring adherence should be based on the usefulness and reliability of the method in light of the researcher's or clinician's goals, taking into account the advantages and disadvantages of the method. The current paper aims to summarize the available measurement methods with their strengths and weaknesses and to present the published studies on adherence within the Hungarian population. The evaluated survey results suggest the importance to improve patient adherence in Hungary. Health care professionals, especially pharmacists have potential influence on adherence and patient's behaviour. It is hoped that this review will lead to help policy development and action to enhance adherence.

Proton speciation and microspeciation of serotonin and 5-hydroxytryptophan.

Protonation equilibria of the neurotransmitter serotonin and its precursor 5-hydroxytryptophan (5-HTP) are characterized at the macroscopic and microscopic levels. 1H-NMR-pH and UV-pH titrations were carried out to determine the macroconstants. Microconstants were obtained by appropriate combination of interactivity parameters and model compounds, allowing the calculation of all the twelve microconstants, the eight microspecies concentrations, and three site-interactivity parameters of 5-HTP, for which no microconstants have been reported earlier. NMR-pH Profiles, macro- and microscopic protonation schemes, and species-specific distribution diagrams are presented. The physicochemical data obtained can help to understand the steric and electronic features governing the selectivity of binding and to design new therapeutic agents.