Reimbursement Of Orphan Drugs Research Articles

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.

Analysing criteria for price and reimbursement of orphan drugs in Spain

ObjectiveThere are differences between countries regarding data requirements for orphan drug evaluation and it is also unknown which criteria might determine the price and reimbursement decision. This study aimed to identify the key criteria for price and reimbursement of orphan drugs in Spain, approved by the European Commission, between January 2012 and June 2018. MethodA descriptive analysis of the orphan drugs and its characteristics was performed. Outcomes criteria assessed were: therapeutic area, existence of alternative treatment, rarity of the disease, clinical trial outcomes and therapeutic positioning report assessment. Hypotheses for each variable regarding Spanish pricing and reimbursement were made and tested with two regression analyses. ResultsOut of 78 orphan drugs approved by the European Commission, 82.1% asked pricing and reimbursement in Spain. From this, 43.8% had pricing and reimbursement approved and 20.3% rejected. Mean time from Spanish marketing authorisation approval to pricing and reimbursement approval was 12.1 ± 5.1 months. Having a positive therapeutic positioning report and no therapeutic alternatives would be associated with a positive pricing and reimbursement in Spain. ConclusionsIt remains challenging to establish which are the driving criteria for pricing and reimbursement approval of orphan drugs in Spain. Further research should be done including other variables that might influence the pricing and reimbursement final decision in Spain.

A IMPORTANCE OF RARE DISEASES AWARENESS FOR MEDICAL AND NURSING STUDENTS AT KSA

Consequently, there is a need to increase the standards of medical education in the field of Rare Diseases and to revise the undergraduate and postgraduate training programs. However, while studies on medical education in the field of RDs has been conducted in various countries across the both Americas, Asia or the European Union, still little is known about the awareness of RDs among healthcare professionals in the kingdom of Saudi Arabia. Thus, we conducted a survey among 200 medical students and 200 nursing students from the college of applied medical sciences at aseer region. The questionnaire assessed their knowledge about the number, examples, aetiology and estimated frequency of RDs. It also evaluated respondents’ self-assessment of competence in RDs. Although the majority of respondents agreed that RDs constitute a serious public health issue both medical students and nursing students showed insufficient knowledge on the aetiology, epidemiology and prevalence of RDs, and many had problems with separating RDs from more common disorders. Moreover, they also lacked knowledge about and the central register of RD patients and reimbursement of orphan drugs in Saudi Arabia. Finally, while almost half respondents declared having had classes about RDs during their studies most perceived their knowledge about RDs as insufficient or poor and felt unprepared for caring for RD patients. Additionally, although majority of respondents in both groups believed that all physicians, regardless of their specialization, should possess knowledge on RDs many respondents did not look for such information at all. While genetics constitutes an important part of medical education, one can observe a lack of knowledge about rare diseases (RD) among medical students and healthcare professionals. Meanwhile, many RD are life threatening and chronically debilitating conditions that significantly reduce patients' quality of life. Most RD patients experience various psychiatric symptoms, behavioural changes and mental retardation. Consequently, physicians should be educated on RD. Thus, the aim of this paper is to assess the knowledge about RD among future medical professionals.

HTA65 Societal and Governmental Perspective of Orphan Drugs - Is There an Impact on Value?

As of January 2022, a new unique pathway for reimbursement of orphan drugs was opened in the Czech Republic. After one year, an evaluation of its effects is in order. We therefore set out to:

Orphan drugs' clinical uncertainty and prices: Addressing allocative and technical inefficiencies in orphan drug reimbursement.

Legislations incentivising orphan drug development and scientific advances have made orphan drugs pharma's high-end favourite for the past two decades. Currently, around 50% of new marketing authorizations are for orphan drugs. For third-party healthcare payers ("payers") the rise of orphan drugs presents new challenges, including a high degree of uncertainty around clinical benefits and harms, a moderate effect size (for many orphan drugs), and a high price tag. The association of high clinical uncertainty and moderate effect sizes is not surprising in small target populations but in combination with high prices creates the risk of allocative and technical inefficiencies for payers. We here discuss and illustrate these risks. A combination of policies is needed for mitigation of allocative inefficiency: while there may be a rationale for higher prices for orphan than non-orphan drugs, a focus of pricing and reimbursement negotiations should include considerations of product profitability and of the consequences of orphan drug costs on the distribution inequality of medication costs for individual insured persons, coupled to knowledge generation from reimbursement contracts covering high-price orphan drugs that would benefit the wider patient community. Performance-based managed entry agreements could help to de-risk the economic consequences of clinical uncertainty and to mitigate technical inefficiency.

HPR17 Changing Landscape of Orphan Drug Reimbursement - Evidence From EU-4 and England

HPR17 Changing Landscape of Orphan Drug Reimbursement - Evidence From EU-4 and England

HPR123 CEE: Brief Overview of Orphan Drug Reimbursement and Selected Clinical Characteristics

Policymakers in different countries consider various aspects of orphan drug reimbursement. In Central and Eastern European (CEE) countries, some common characteristics can be seen when it comes to strategies for drug policy. We decided to investigate which aspects of the clinical data from orphan drugs might affect drug reimbursement in selected CEE countries.

OP90 Optimizing Health Technology Assessment And Appraisal For Orphan Drug Reimbursement: Experiences And Tools For Improvement

IntroductionThe very high costs of orphan drugs, together with the uncertainties regarding their (cost-)effectiveness raise questions regarding the efficiency and legitimacy of their health technology assessment (HTA) and appraisal process. The aim of the present, qualitative study was to investigate how experts on the reimbursement of these treatments perceive the HTA and appraisal process in their country. Moreover, it aimed to provide specific conditions and practical recommendations for their improvement.MethodsTwenty-two European experts from 19 different countries were included in a qualitative survey and semi-structured interviews. Transcripts were analyzed using the qualitative data analysis software Nvivo. A grounded theory approach was adopted to develop a set of well-defined concepts from the cyclic analysis of the empirical data.ResultsFirst, analysis of the expert interviews yielded five good practices for an efficient HTA and appraisal of orphan drugs: a high level of transparency, patient involvement, a clear decision-making structure with room for flexibility, mechanisms to minimize bias and an explicit consideration of the opportunity cost. Meanwhile, participants highlighted several barriers to the overall process, such as a lack of trust between the different stakeholders and imbalances in negotiation power. In addition, the results allowed to identify a number of ‘contextual’ determinants that may undermine the legitimacy of the final decision, such as bias and the perverse effects of the orphan drug legislation. Drawing from the experts’ experiences, a toolkit was developed that includes an extensive number of specific recommendations (and conditions) for decision-makers to improve the legitimacy and efficiency of their HTA and appraisal of orphan drugs.ConclusionsOverall, the results showed that decision-makers should focus on limiting the impact of the contextual determinants rather than improving the methods included in the HTA. This will contribute to further legitimize reimbursement choices for orphan drugs towards the wider public.

How Can We Optimize the Value Assessment and Appraisal of Orphan Drugs for Reimbursement Purposes? A Qualitative Interview Study Across European Countries.

Introduction: The expansion of orphan drug treatment at increasing prices, together with uncertainties regarding their (cost-)effectiveness raises difficulties for decision-makers to assess these drugs for reimbursement. The present qualitative study aims to gain better insight into current value assessment and appraisal frameworks for orphan drugs, and provides guidance for improvement. Methods: 22 European experts from 19 different countries were included in a qualitative survey, followed by in-depth semi-structured interviews. These experts were academics, members of reimbursement agencies or health authorities, or members of regulatory or health/social insurance institutions. Adopting a Grounded Theory approach, transcripts were analysed according to the QUAGOL method, supported by the qualitative data analysis software Nvivo. Results: Although participants indicated several good practices (e.g., the involvement of patients and the presence of structure and consistency), several barriers (e.g., the lack of transparency) lead to questions regarding the efficiency of the overall reimbursement process. In addition, the study identified a number of “contextual” determinants (e.g., bias, perverse effects of the orphan drug legislation, and an inadequate consideration of the opportunity cost), which may undermine the legitimacy of orphan drug reimbursement decisions. Conclusion: The present study provides guidance for decision-makers to improve the efficiency of orphan drug reimbursement. In particular, decision-makers can generate quick wins by limiting the impact of contextual determinants rather than improving the methods included in the HTA. When implemented into a framework that promotes “Accountability for Reasonableness” (A4R), this allows decision-makers to improve the legitimacy of reimbursement decisions concerning future orphan drugs.

The Awareness of Rare Diseases Among Medical Students and Practicing Physicians in the Republic of Kazakhstan. An Exploratory Study.

Although national plans or strategies for rare diseases (RDs) have been implemented in many jurisdictions research show that one of the main barriers RD patients face during medical encounter is medical professionals' low level of knowledge and experience on the diagnosis, treatment and rehabilitation of RD patients. Consequently, there is a need to increase the standards of medical education in the field of RDs and to revise the undergraduate and postgraduate training programs. However, while studies on medical education in the field of RDs has been conducted in various countries across the both Americas, Asia or the European Union, still little is known about the awareness of RDs among healthcare professionals in the Republic of Kazakhstan. Thus, we conducted a survey among 207 medical students and 101 medical doctors from the West Kazakhstan Marat Ospanov Medical University, Aktobe, Kazakhstan. The study was conducted between March and May 2021. The questionnaire assessed their knowledge about the number, examples, etiology and estimated frequency of RDs. It also evaluated respondents self-assessment of competence in RDs. Although the majority of respondents agreed that RDs constitute a serious public health issue both medical students and medical doctors showed insufficient knowledge on the etiology, epidemiology and prevalence of RDs, and many had problems with separating RDs from more common disorders. Moreover, they also lacked knowledge about and the central register of RD patients and reimbursement of orphan drugs in Kazakhstan. Finally, while almost half respondents declared having had classes about RDs during their studies most perceived their knowledge about RDs as insufficient or poor and felt unprepared for caring for RD patients. Additionally, although majority of respondents in both groups believed that all physicians, regardless of their specialization, should possess knowledge on RDs many respondents did not look for such information at all.

An international comparative analysis of public reimbursement of orphan drugs in Canadian provinces compared to European countries

BackgroundThe Canadian government has committed to developing a national strategy for drugs for rare diseases starting in 2022. Considering this announcement, we conducted a comparative analysis to examine patient access to therapies for rare disease in Canada relative to Europe and the U.S.MethodsGiven its similarity to the Canadian health care system, we used Europe as the reference point to analyze all of the therapies with an orphan drug designation approved by the European Medicine Agency (EMA) from 1 January 2015 to 31 March 2020. We then contrasted access to these drugs in Canada (Health Canada) and the U.S. (Food and Drug Administration, FDA). We focused on: (1) the number of therapies for rare diseases entering the Canadian market; (2) the percentage of these therapies that are publicly available to Canadians; and (3) the timelines for patients to access these therapies in Canada.ResultsSixty-three approved therapies with an orphan drug designation from the EMA were identified. Fifty-three (84%) of these drugs had also been submitted to the FDA for approval, and 41 (65%) were submitted to Health Canada for approval. In Europe, Germany, Denmark, and the U.K. had the highest percentage of publicly reimbursed orphan drugs (84%, 70%, 68%, respectively). In comparison, Ontario (32%), Quebec (25%), and Alberta (25%) had the highest percentage of drugs reimbursed among the Canadian provinces. The shortest median duration (in months) from EMA approval to jurisdictional decision on reimbursement was in Austria (3.2), followed by Germany (4.1), and Finland (6.0). In Canada, the shortest median duration (in months) from regulatory approval to reimbursement was in British Columbia (17.3), Quebec (19.6) and Manitoba (19.6), while the longest duration was in P.E.I (38.5), followed by Nova Scotia (25.9), and Newfoundland (25.1).ConclusionsOur comparative analysis found that relative to the EU Canadians had less frequent and timely access to therapies for rare diseases. This highlights the need for a rare disease strategy in Canada that allows for clear identification and transparent tracking of the pathway for rare disease drugs, and ultimately optimizes the number of patients with access to these therapies.

How to Value Orphan Drugs? A Review of European Value Assessment Frameworks.

Background: Decision-makers have implemented a variety of value assessment frameworks (VAFs) for orphan drugs in European jurisdictions, which has contributed to variations in access for rare disease patients. This review provides an overview of the strengths and limitations of VAFs for the reimbursement of orphan drugs in Europe, and may serve as a guide for decision-makers. Methods: A narrative literature review was conducted using the databases Pubmed, Scopus and Web of Science. Only publications in English were included. Publications known to the authors were added, as well as conference or research papers, or information published on the website of reimbursement and health technology assessment (HTA) agencies. Additionally, publications were included through snowballing or focused searches. Results: Although a VAF that applies a standard economic evaluation treats both orphan drugs and non-orphan drugs equally, its focus on cost-effectiveness discards the impact of disease rarity on data uncertainty, which influences an accurate estimation of an orphan drug’s health benefit in terms of quality-adjusted life-years (QALYs). A VAF that weighs QALYs or applies a variable incremental cost-effectiveness (ICER) threshold, allows the inclusion of value factors beyond the QALY, although their methodologies are flawed. Multi-criteria decision analysis (MCDA) incorporates a flexible set of value factors and involves multiple stakeholders’ perspectives. Nevertheless, its successful implementation relies on decision-makers’ openness toward transparency and a pragmatic approach, while allowing the flexibility for continuous improvement. Conclusion: The frameworks listed above each have multiple strengths and weaknesses. We advocate that decision-makers apply the concept of accountability for reasonableness (A4R) to justify their choice for a specific VAF for orphan drugs and to strive for maximum transparency concerning the decision-making process. Also, in order to manage uncertainty and feasibility of funding, decision-makers may consider using managed-entry agreements rather than implementing a separate VAF for orphan drugs.

A multi-stakeholder multicriteria decision analysis for the reimbursement of orphan drugs (FinMHU-MCDA study)

BackgroundPatient access to orphan medicinal products (OMPs) is limited and varies between countries, reimbursement decisions on OMPs are complex, and there is a need for more transparent processes to know which criteria should be considered to inform these decisions. This study aimed to determine the most relevant criteria for the reimbursement of OMPs in Spain, from a multi-stakeholder perspective, and using multicriteria decision analysis (MCDA).MethodsAn MCDA was developed in 3 phases and included 28 stakeholders closely related to the field of rare diseases (6 physicians, 5 hospital pharmacists, 7 health economists, 4 patient representatives and 6 members from national and regional health authorities). Initially [phase A], a bibliographic review was conducted to identify the potential reimbursement criteria. Then, a reduced advisory board (8 members) proposed, selected, and defined the final list of criteria that could be relevant for reimbursement. A discrete choice experiment (DCE) [phase B] was developed to determine the relevance and relative importance weight of such criteria according to the stakeholders’ preferences by choosing between pairs of hypothetical financing scenarios. A multinomial logit model was fitted to analyze the DCE responses. Finally [phase C], the advisory board review the results using a deliberative process.ResultsThirteen criteria were selected, related to 4 dimensions: patient population, disease, treatment, and economic evaluation. Nine criteria were deemed relevant for decision-making and associated with a higher relative importance: Health-related quality of life (HRQL) (23.53%), treatment efficacy (14.64%), availability of treatment alternatives (13.51%), disease severity (12.62%), avoided costs (11.21%), age of target population (7.75%), safety (seriousness of adverse events) (4.72%), quality of evidence (3.82%) and size of target population (3.12%). The remaining criteria had a < 3% relative importance: economic burden of disease (2.50%), cost of treatment (1.73%), cost-effectiveness (0.83%) and safety (frequency of adverse events) (0.03%).ConclusionThe reimbursement of OMPs in Spain should be determined by its effect on patient’s HRQL, the extent of its therapeutic benefit from efficacy and the availability of other therapeutic options. Furthermore, the severity of the rare disease should also influence the decision along with the potential of the treatment to avoid associated costs.

RO4 Comparison of Health Technology Assessments and Time to Reimbursement for Orphan Drugs from FOUR HTA Agencies: Opportunities and Challenges in France, Germany, England and Scotland

RO4 Comparison of Health Technology Assessments and Time to Reimbursement for Orphan Drugs from FOUR HTA Agencies: Opportunities and Challenges in France, Germany, England and Scotland

PRO65 Time to Reimbursement for Orphan Drugs in EU5 in the Last FIVE YEARS

The primary objective of this analysis was to compare the time to reimbursement (TTR) of orphan drugs (ODs) in five European countries: France, Germany, Italy, Spain and the United Kingdom (UK). A panel of 54 ODs with new active substances was created by selecting those approved by the EMA in the last 5 years. The dates of national reimbursement for these were also collected in each country from respective national authorities. TTR was defined as a difference between the date of the national approval/commercialization and the EC decision. The mean difference time to reimbursement varied considerably across countries, ranging in Germany from immediate reimbursement available after launch, “real time launch” 99 days (median 37) to 559 days (median 552) in Spain, passing through 281 days (median 227) in France, 463 days (median 350) in UK and 458 days (median 417) in Italy. Even within each single country ranges between min and max time to reimbursement were highly heterogeneous: 72-902 days for France; 67-1078 days for Italy; 132-1390 days for Spain; 135 - 1168 days for UK. Although drug's launch in Germany is possible immediately after the EC decision, ODs were commercialized within a timeframe of 7-826 days. The overall percentage of reimbursed drugs ranged from 51% in Spain to 95% in Germany; 68% in UK, 72% in Italy and 91% in France. Our analysis demonstrates a wide difference in TTR timelines, related to a great heterogeneity of assessment procedures applied across Europe. Current data also show that patients in Germany and France, compared to Italy, Spain and UK, have a faster access to ODs.

PRO81 Is EU Orphan Medicine Status Working? a Retrospective Analysis of Orphan Drug Reimbursement in England

PRO81 Is EU Orphan Medicine Status Working? a Retrospective Analysis of Orphan Drug Reimbursement in England

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

BackgroundThe 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.ResultsA 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]).ConclusionsIn 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.

Share your rare with care: a patient corner for the European Reference Networks on Rare Disease

Abstract Background The European Reference Network on Rare Disease (ERN) is focused on providing more equitable care across Europe and creates a network of both medical specialists and patient experts. One relevant objective of the activities planned into the ERNs is to address the economic dimensions of rare diseases in order to develop strategies to improve research and patients' access to orphan drugs (ODs) and highly specialized health technologies. The themes built in these preliminary years were directed toward guidelines and policies concerning reimbursement of ODs and direct provision by the healthcare system. Methods to proceed further in humanization of care we establish involvement of patients' associations in decision making and implementation of clinical practice guidelines. We built in Federico II University Hospital where 12 ERN were aligned a front office corner shared between patients association and hospital direction in order to face the patient difficulties along the pathway. The corner is open three times a week on the morning, with a dedicated phone number. Results Main issues regarded the understanding of the disease and the diagnosis (ie, lack of familiarity with the rare disease, disease heterogeneity, lack of established diagnostic criteria, misdiagnosis,) the development of effective treatments and the need for efficacy along the path way of care (ie, geographical limitations, disease coding systems, ethical and privacy issues). Fewer concerns were about the equity of access and other social pressures. Conclusions In general, in ERN context, few people declared to work in human and social issues, including research on patient's quality of life, patient's awareness, or methods for social support. Our findings demonstrated that Patients were positively affected from the corner initiative: this may ameliorate the use of infrastructures offering services, also that rarely known as national and international biobanking platforms, registries and networks. Key messages Humanization of care issues and strategies are nowadays mandatory in rare diseases. Patients are positively affected from shared initiatives.

Affordability of in vivo gene therapy. Problems and potential solutions

Aim. To review foreign approaches to the evaluation and financing of in vivo gene therapy drugs. Materials and Methods. The first stage of the review included the systematic search for publications of clinical-economic studies (CES) on in vivo gene therapy drugs registered on the international pharmaceutical market. The analysis of the methodology used in the found CESs was performed based on the given criteria. The second and third stages of the review included the search for the information on the approaches and results of the evaluation of in vivo gene therapy drugs by foreign agencies on the assessment of healthcare technologies (AHT) and the implemented approaches to the financing of expensive medical technologies. Results. Totally, four in vivo gene therapy drugs registered on the foreign markets were found: talimogene laherparepvec (Imlygic), voretigene neparvovec (Luxturna), onasemnogene abeparvovec (Zolgensma), and alipogene tiparvove (Glybera). The analysis of the methodology of CES on in vivo gene therapy drugs did not reveal general methodological peculiarities. The analysis of the approaches to the reimbursement for the cost of these four drugs in the European countries showed that there were no special procedures intended for gene drugs. However, in the majority of countries, there are some mechanisms of reimbursement for orphan drugs and the majority of the above-mentioned in vivo gene therapy drugs are orphan. It was revealed that the most perspective methods of payment for in vivo gene therapy drugs were installment payments, risk-sharing agreements, and their combinations. Still, none of these payment methods are implemented in Russia because of the lack of regulatory and legal framework. Conclusion. The design and methodological peculiarities of CES on in vivo gene therapy drugs are similar to orphan drugs (in some countries, there is a special flexible procedure). In the Russian Federation, there is no special procedure of ATH for orphan drugs, which can provide difficulties in the reimbursement for these drugs. Besides, in the Russian Federation, the issue of the implementation of innovative models for drugs provision (risk-sharing, installment payments is acute). The changes in this area would also lead to the optimization of the influence of expensive healthcare technologies on the budget of the system of healthcare.

Access and Unmet Needs of Orphan Drugs in 194 Countries and 6 Areas: A Global Policy Review With Content Analysis.

Three hundred million people living with rare diseases worldwide are disproportionately deprived of in-time diagnosis and treatment compared with other patients. This review provides an overview of global policies that optimize development, licensing, pricing, and reimbursement of orphan drugs. Pharmaceutical legislation and policies related to access and regulation of orphan drugs were examined from 194 World Health Organization member countries and 6 areas. Orphan drug policies (ODPs) were identified through internet search, emails to national pharmacovigilance centers, and systematic academic literature search. Texts from selected publications were extracted for content analysis. One hundred seventy-two drug regulation documents and 77 academic publications from 162 countries/areas were included. Ninety-two of 200 countries/areas (46.0%) had documentation on ODPs. Thirty-four subthemes from content analysis were categorized into 6 policy themes, namely, orphan drug designation, marketing authorization, safety and efficacy requirements, price regulation, incentives that encourage market availability, and incentives that encourage research and development. Countries/areas with ODPs were statistically wealthier (gross national income per capita= $10 875 vs $3950, P < .001). Country/area income was also positively correlated with the scope of the respective ODP (correlation coefficient= 0.57, P < .001). Globally, the number of countries with an ODP has grown rapidly since 2013. Nevertheless, disparities in geographical distribution and income levels affect the establishment of ODPs. Furthermore, identified policy gaps in price regulation, incentives that encourage market availability, and incentives that encourage research and development should be addressed to improve access to available and affordable orphan drugs.