Clinical aspects of reimbursement policies for orphan drugs in Central and Eastern European countries.

Objectives: The aim of this study was to characterize the reimbursement policy for orphan drugs (ODs) in Central and Eastern European (CEE) countries in relation to the availability and impact of clinical evidence, health technology assessment (HTA) procedure, selected economic indicators, and the drug type according to indications. Materials and methods: A list of authorized medicines with orphan designation and information about active substance, Anatomical Therapeutic Chemical (ATC) classification, and therapeutic area was extracted from the web-based register of the European Medicines Agency (EMA). A country-based questionnaire survey was performed between September 2021 and January 2022 in a group of selected experts from nine CEE countries (an invitation was sent to 11 countries). A descriptive and statistical analysis was conducted to determine statistical significance, correlations, between the drug or country characteristic and the positive recommendation or reimbursement of ODs. Results: The proportion of reimbursed orphan drugs differed between countries, ranging from 17.7% in Estonia to 49.6% in Hungary (p < 0.001). The odds that ODs were reimbursed were reduced in countries with a "strong" level of impact of drug safety and efficacy on reimbursement decisions (p=0.018), the presence of other additional specific clinical aspects (e.g., genomic data) considered in the reimbursement decision (p < 0.001) and mandatory (without exception) safety assessments (p=0.004). The probability that ODs were reimbursed was increased in countries with a "moderate" level of impact of drug safety and efficacy on reimbursement decisions (p=0.018), when reimbursement decisions are dependent on the EMA registration status and orphan drug designation (p < 0.001), the presence of the "positive HTA recommendation guarantees reimbursement" policy (p < 0.001), higher GDP per inhabitant (p=0.003), and higher healthcare expenditure (p < 0.001). Conclusion: We found that there are differences among CEE countries in the reimbursement of orphan drugs, and we identified aspects that may influence these differences. Safety, efficacy, and specific clinical aspect issues significantly influenced reimbursement decisions. Antineoplastic and immunomodulating agents drugs were the largest group of ODs and increased the chance of getting a positive recommendation. The higher GDP per inhabitant and healthcare expenditures per inhabitant were positively linked to the chance that an OD receives reimbursement.

EQ-5D-5L: a value set for Romania.

OBJECTIVE: We aimed to develop an EQ-5D-5L value set for Romania. METHODS: In line with the EuroQoL standardized valuation protocol, computer-assisted interviews were conducted face-to-face in a representative sample in Romania (November 2018-November 2019). Valuation methods included composite time trade-off and discrete choice experiment tasks. Several models were tested, including models that accounted for data censoring, panel structure of the data, heteroscedasticity, conditional logit, and hybrid models. The final model was selected based on logical consistency, theoretical considerations, and use of all available data. We compared our value set with other value sets from Central and Eastern Europe region. RESULTS: Data from 1493 respondents was used to estimate the value set. A censored hybrid model corrected for heteroscedasticity was selected to represent the value set. The highest decrements in utility were observed for the pain/discomfort dimension (0.375), followed by the mobility dimension (0.293). Health utilities ranged from 1.000 to - 0.323 and 1.3% of the values were negative. The model was corrected with survey weights to better reflect the representativeness of the sample, but the first two coefficients of the self-care dimension stopped being logically consistent. Differences were found between the Romanian, Hungarian and Polish EQ-5D-5L value sets. Good agreement was noted with the Romanian EQ-5D-3L value set, with a swap between pain/discomfort and mobility in ranking of dimensions. CONCLUSION: A value set for EQ-5D-5L is now available for Romania. This will push one-step further the development of health technology assessment and encourage more health-related quality-of-life research to be conducted locally.

Estimating an EQ-5D-3L Value Set for Romania Using Time Trade-Off.

OBJECTIVE: To provide health-related quality of life (HRQoL) data to support health technology assessment (HTA) and reimbursement decisions in Romania, by developing a country-specific value set for the EQ-5D-3L questionnaire. METHODS: We used the cTTO method to elicit health state values using a computer-assisted personal interviewing approach. Interviews were standardized following the most recent version of the EQ-VT protocol developed by the EuroQoL Foundation. Thirty EQ-5D-3L health states were randomly assigned to respondents in blocks of three. Econometric modeling was used to estimate values for all 243 states described by the EQ-5D-3L. RESULTS: Data from 1556 non-institutionalized adults aged 18 years and older, selected from a national representative sample, were used to build the value set. All tested models were logically consistent; the final model chosen to generate the value set was an interval regression model. The predicted EQ-5D-3L values ranged from 0.969 to 0.399, and the relative importance of EQ-5D-3L dimensions was in the following order: mobility, pain/discomfort, self-care, anxiety/depression, and usual activities. CONCLUSIONS: These results can support reimbursement decisions and allow regional cross-country comparisons between health technologies. This study lays a stepping stone in the development of a health technology assessment process more driven by locally relevant data in Romania.

Health technology assessment and reimbursement policy for oncology orphan drugs in Central and Eastern Europe.

BACKGROUND: The reimbursement of orphan drugs (OD) is an increasingly important for country policymakers, and still insufficiently understood, especially in Central and Eastern Europe. The aim of this research was to provide a comprehensive description of country-specific health technology assessment (HTA) policies as well as evaluate the percentage of HTA recommendations and reimbursement decisions for oncology OD. In addition, the study was designed to elucidate the impact of reimbursement of these drugs on the public budget and the agreement between HTA recommendations and reimbursement decisions in the analysed countries. A questionnaire survey was used to collect data on the reimbursement status, HTA recommendation, marketing authorisation, and public expenses on reimbursement in 2014, 2015, and 2016 for all oncology drugs with an orphan designation by the European Medicine Agency in 2017 in Bulgaria, Croatia, Czechia, Estonia, Hungary, Latvia, Lithuania, Poland, Romania, and Slovakia. The agreement between the HTA recommendation and reimbursement status was assessed using the kappa coefficient. The Pearson's correlation was used to analyse the relationship between gross domestic product (GDP) and GDP per capita and reimbursement expenses. RESULTS: A total of 36 drugs were analysed (25% conditionally approved; 5.56% approved under exceptional circumstances). The share of reimbursed drugs ranged from 11.11% in Latvia to 41.67% in Poland. The highest share of positive recommendations was observed for Bulgaria and Estonia (36.11%), and the lowest, for Latvia (11.11%). The agreement varied from 0.4 for Poland to 1 for Latvia, Hungary, and Slovakia. Expenses were correlated with GDP (0.95 [0.81-0.99]), and not with GDP per capita (0.54 [- 0.136 to 0.873]). Expenses per capita were not correlated with GDP per capita (0.52 [- 0.15 to 0.87]). CONCLUSIONS: In Hungary, Latvia, and Slovakia, a positive recommendation was associated with a reimbursement, and a negative one, with the lack of reimbursement. The reimbursement of oncology OD is associated with a growing burden for public budget, and the expenses are correlated with the total GDP. The highest share of drugs with any recommendation was observed in Poland, and the lowest, in Latvia and Romania. The share of reimbursed drugs was the lowest in Latvia and the highest in Poland.

Measuring health-related quality of life in the general population and Roma communities in Romania: study protocol for two cross-sectional studies.

INTRODUCTION: The importance of health-related quality of life (HRQoL) is increasing and many healthcare authorities recommend the use of measures that account for both mortality and morbidity. This study will determine, for the first time in Romania, value sets for EuroQoL-five-dimensions-3-level (EQ-5D-3L) and EQ-5D-5L questionnaires and their population norms (study 1). It will also compare the HRQoL (measured with EQ-5D-5L) of Roma communities in Romania with that of the general population (study 2). METHODS AND ANALYSIS: Cross-sectional studies of face-to-face interviews conducted in representative samples of the Romanian general population and Romanian Roma communities. 1614 non-institutionalised adults older than 18 years will be interviewed using a computer-assisted interview for study 1. Participants will complete EQ-5D-3L and 5L, 13 composite time trade-off tasks (cTTO), 7 discrete choice experiment questions (DCE) and sociodemographic questions. For study 2, 606 non-institutionalised self-identified Roma people older than 18 years will be interviewed using a pencil-and-paper interview. Participants will complete EQ-5D-5L and the same sociodemographic questions as for study 1. The 3L value set will be estimated using econometric models and the cTTO data. cTTO and DCE data will be used for the 5L value set. Population norms will be reported by age and gender. The ORs for reporting different levels of problems and the most common health states in the population will be estimated. For study 2, t-tests and analysis of variance will be used to explore differences between groups in HRQoL and for each EQ-5D. ETHICS AND DISSEMINATION: Ethics approval was given by the National Bioethics Committee of Medicines and Medical Devices Romania and Newcastle University's Research Ethics Committee. Results will be published in peer-reviewed journals, presented at scientific conferences and on the project's website. The EQ-5D-5L anonymised datasets will be deposited in a centralised repository. Two public workshops with local authorities, physicians and patients' associations will be held.

Analysis of the Indirect Costs of Rheumatoid Arthritis in Romania.

Rheumatoid arthritis (RA) is associated with increased costs generated by resource utilization and loss of work productivity. We have studied 206 RA patients and analyzed indirect costs of RA in Romania (estimated using the human capital approach) in comparison with reported data for other countries. Data were collected using self-reported questionnaires. The average age at inclusion was 55 years, with mean disease duration of 9.4 years; 55 patients had permanent work disability due to RA; 6.35 days of sick leave per patient were reported for the entire year of follow-up; the cost of permanent work disability was 1256€ per patient. From a societal perspective, the average indirect costs for a patient with RA were 1506€, significantly lower than the ones reported by other countries, especially due to the low monetary value of paid work.