Compliance with Pregnancy Prevention Recommendations for Isotretinoin Following the Amendment of the European Union Pregnancy Prevention Program: A Repeat Study in Estonia.

BACKGROUND: Isotretinoin, indicated for severe acne, is a potent teratogen and therefore contraindicated in pregnancy. Thus, the pregnancy prevention program (PPP) for isotretinoin has been introduced. OBJECTIVES: The aim of this study was to assess the concomitant use of isotretinoin and effective contraception and the rate of potential isotretinoin-exposed pregnancies in females of childbearing age in 2017-2020 in Estonia. In addition, we aimed to evaluate whether compliance with the PPP has improved compared with the previous study conducted in Estonia covering the period of 2012-2016. METHODS: This retrospective, nationwide study using prescription and healthcare claims data included 2575 females aged 15-45 years who started using isotretinoin between 2017 and 2020. RESULTS: For 64.7% of females of childbearing age, no concurrent use of an effective contraceptive was detected while using isotretinoin. A moderately higher contraceptive coverage (35.3%) was observed compared with the previous study (29.7%) (p < 0.001). Complete contraception coverage was highest in females aged 30-39 years with an adjusted OR of 12.8 (p < 0.001) compared with the age group 15-19 years and 2.47 (p < 0.001) compared with the age group 20-29 years. 17 pregnancies coincided with the isotretinoin treatment-related period. The risk for potential isotretinoin-exposed pregnancy was 6.6 (95% CI 3.9-10.5) per 1000 treated females of childbearing age over the 4-year observation period. The risk for potential isotretinoin-exposed pregnancies per 1000 treated females was 1.0 in females aged 15-19 years, 11.6 in females aged 20-29 years, 8.8 in females aged 30-39 years, and 7.4 in females aged 40-45 years (p = 0.009). CONCLUSION: A slight improvement in complete contraceptive coverage during isotretinoin use has not resulted in a decrease in the risk of isotretinoin-exposed pregnancies. The contraceptive usage and risk for pregnancy vary greatly across age groups, suggesting the need for a more targeted approach to improve the effectiveness of the PPP.

Corrigendum to "Utilisation Trend of Long-Acting Insulin Analogues including Biosimilars across Europe: Findings and Implications".

[This corrects the article DOI: 10.1155/2021/9996193.].

Implementation of European Cross-border Electronic Prescription and Electronic Dispensing Service: Cross-sectional Survey.

BACKGROUND: The European cross-border electronic prescription (CBeP) and cross-border electronic dispensing system was first implemented in January 2019 when it became possible to purchase medications from community pharmacies in Estonia using a Finnish ePrescription. In 2020, Estonian ePrescriptions became available to be dispensed in Finnish pharmacies. The CBeP is an important milestone in increasing access to medicines across the European Union, and it has been unstudied to date. OBJECTIVE: This study aimed to investigate Estonian and Finnish pharmacists' experiences of factors influencing access to, and dispensing of, CBePs. METHODS: A web-based survey was conducted among Estonian and Finnish pharmacists between April and May 2021. The survey was distributed to all 664 community pharmacies (n=289, 43.5% in Estonia and n=375, 56.5% in Finland) where CBePs had been dispensed in 2020. The data were analyzed using frequencies and a chi-square test. Answers to open-ended questions were categorized using content analysis and then analyzed by frequency. RESULTS: In total, 66.7% (84/126) of the responses from Estonia and 76.6% (154/201) of the responses from Finland were included in the study. The majority of Estonian (74/84, 88%) and Finnish (126/154, 81.8%) respondents agreed that CBePs have improved patients' access to medications. Problems with the availability of medications when dispensing CBePs were reported by 76% (64/84) of the Estonian respondents and 35.1% (54/154) of the Finnish respondents. In Estonia, the most commonly reported availability problem concerned the same active ingredient (49/84, 58%) of the medication not being available in the market, whereas in Finland, the most common issue was the unavailability of equivalent package size in the market (30/154, 19.5%). Encountering ambiguities or errors in the CBePs was reported by 61% (51/84) of the Estonian respondents and 42.8% (66/154) of the Finnish respondents. Mostly, the availability issues and ambiguities or errors were encountered rarely. The most commonly encountered ambiguities or errors were incorrect pharmaceutical form (23/84, 27%) in Estonia and incorrect total amount of medication (21/154, 13.6%) in Finland. Technical problems with using the CBeP system were reported by 57% (48/84) of the Estonian respondents and 40.2% (62/154) of the Finnish respondents. Most of the Estonian and Finnish respondents (53/84, 63%, and 133/154, 86.4%, respectively) had access to guidelines for dispensing CBePs. More than half of the Estonian (52/84, 62%) and Finnish (95/154, 61.7%) respondents felt that they had received sufficient training on dispensing CBePs. CONCLUSIONS: Pharmacists in both Estonia and Finland agreed that CBePs improve access to medications. However, interfering factors, such as ambiguities or errors in CBePs and technical problems in the CBeP system, can reduce access to medications. The respondents had received sufficient training and were informed of the guidelines; however, they felt that the content of the guidelines could be improved.

Outpatient fluoroquinolone use in relation to European Medicines Agency's recommendation: An Estonian nationwide drug utilization study.

PURPOSE: To determine possible changes in prescribing of fluoroquinolones in relation to the European Medicines Agency's (EMA) recommendation in October 2018. METHODS: We conducted a nationwide time-series study on outpatient use of fluoroquinolones during January 2016-June 2021 in Estonia. Joinpoint regression was used to identify change points over time. Several subgroup analyses by prescriber specialty, indication group, risk factors for tendon injury, aortic aneurysm/dissection or heart valve regurgitation/incompetence and the prescribing of other antibiotics were performed. RESULTS: During the study period 236 989 prescriptions of fluoroquinolones were dispensed to 142 659 persons. The number of episodes per month declined from 3780 (2.9/1000 inhabitants) to 2570 (1.9/1000 inhabitants). We identified three change points with four different trend segments: from January 2016 to November 2018 monthly percent change (MPC) -0.4%, from November 2018 to June 2019 MPC -2.5%, from June 2019 to July 2020 MPC 1.7% and from July 2020 to June 2021 MPC -3.3%. Prescribing for indications which were removed or restricted by EMA's recommendation comprised a small proportion of all fluoroquinolone episodes -2.8% and 6.3%, respectively. The risk factors for tendon injury and for cardiac disorders (aortic aneurysm/dissection or heart valve regurgitation/incompetence) were present in 46.4% and 57.8% episodes of fluoroquinolone users, respectively. No changes in the trend of prescribing to users with risk factors was detected. CONCLUSIONS: The EMA's recommendation may have contributed to the greater decline in the use of fluoroquinolones. However, there is still a high proportion of users with predisposing factors for tendon injury and serious cardiac disorders.

Pre-pregnancy counseling for women with epilepsy: Can we do better?

OBJECTIVE: For many women with epilepsy (WWE), decision making about pregnancy is difficult, due mainly to the potential teratogenic risks of anti-seizure medications (ASMs). Pre-pregnancy counseling is essential to minimize these risks. This study was conducted to assess the rate and effectiveness of pre-pregnancy counseling for women treated with valproate (VPA) in Estonia. METHODS: We used outpatient prescription data from the national health insurance provider to identify all women treated with VPA during 2011-2018 in Estonia. The personal medical documentation of women who became pregnant while on VPA treatment was reviewed. Pre-pregnancy counseling history and VPA-treatment indications were analyzed. RESULTS: Data from 141 women who became pregnant while on VPA treatment during 2011-2018 time period were analyzed. Of these patients, 77% had epilepsy and 19% psychiatric diagnoses. Pre-pregnancy counseling was recorded for 13% (n = 19) of women who later became pregnant. VPA monotherapy and the lack of VPA treatment indication were associated with the lack of counseling before pregnancy. CONCLUSIONS: This study revealed a significant deficit in pre-pregnancy counseling for WWE treated with VPA in Estonia. Awareness of the need for such counseling should be increased among medical specialists.

Utilisation Trend of Long-Acting Insulin Analogues including Biosimilars across Europe: Findings and Implications.

BACKGROUND: Diabetes mellitus rates and associated costs continue to rise across Europe enhancing health authority focus on its management. The risk of complications is enhanced by poor glycaemic control, with long-acting insulin analogues developed to reduce hypoglycaemia and improve patient convenience. There are concerns though with their considerably higher costs, but moderated by reductions in complications and associated costs. Biosimilars can help further reduce costs. However, to date, price reductions for biosimilar insulin glargine appear limited. In addition, the originator company has switched promotional efforts to more concentrated patented formulations to reduce the impact of biosimilars. There are also concerns with different devices between the manufacturers. As a result, there is a need to assess current utilisation rates for insulins, especially long-acting insulin analogues and biosimilars, and the rationale for patterns seen, among multiple European countries to provide future direction. Methodology. Health authority databases are examined to assess utilisation and expenditure patterns for insulins, including biosimilar insulin glargine. Explanations for patterns seen were provided by senior-level personnel. RESULTS: Typically increasing use of long-acting insulin analogues across Europe including both Western and Central and Eastern European countries reflects perceived patient benefits despite higher prices. However, activities by the originator company to switch patients to more concentrated insulin glargine coupled with lowering prices towards biosimilars have limited biosimilar uptake, with biosimilars not currently launched in a minority of European countries. A number of activities were identified to address this. Enhancing the attractiveness of the biosimilar insulin market is essential to encourage other biosimilar manufacturers to enter the market as more long-acting insulin analogues lose their patents to benefit all key stakeholder groups. CONCLUSIONS: There are concerns with the availability and use of insulin glargine biosimilars among European countries despite lower costs. This can be addressed.

Trends in the use of hormonal contraception in Estonia 2005-2019 and the risk of arterial and venous thromboembolism: a population-based study.

PURPOSE: To describe trends in hormonal contraceptive use, incidence of thromboembolism and presence of risk factors for thromboembolism among the users in Estonia. MATERIAL AND METHODS: Data of 223 312 female patients aged 15-49 years in 2005-2019 from national health insurance databases was derived. Annual prevalence rates of hormonal contraceptive users, incidence rates of thromboembolism and prevalence rates of risk factors were calculated. RESULTS: Between 2005-2019 usage of progestogen-only contraceptives (POCs) increased steadily (from 24 to 135 users per 1000 population), whereas combined hormonal contraceptive (CHC) use declined (from 209 in 2012 to 161 users per 1000 population in 2019). During the study period, 390 cases of venous thromboembolism and 108 arterial thromboembolism coincided with hormonal contraceptive use. Incidence rate for venous thromboembolism was 5.0 (95% CI 4.5-5.5) and for arterial thromboembolism 1.4 per 10 000 person-years (95% CI 1.1-1.7) among hormonal contraceptive users. Age adjusted incidence of venous thromboembolism among CHC users was 5.8 (95% CI 4.1-8.2) times higher than in POC users. Among CHC users, 10.3% had more than one risk factor for thrombosis. CONCLUSIONS: In regards to the risk of thromboembolism, wider use of POCs and declining prevalence of CHCs in Estonia is positive trend. Still, women with history of thrombosis receiving CHC is a serious concern.

Potential approaches for the pricing of cancer medicines across Europe to enhance the sustainability of healthcare systems and the implications.

Introduction: There are growing concerns among European health authorities regarding increasing prices for new cancer medicines, prices not necessarily linked to health gain and the implications for the sustainability of their healthcare systems.Areas covered: Narrative discussion principally among payers and their advisers regarding potential approaches to the pricing of new cancer medicines.Expert opinion: A number of potential pricing approaches are discussed including minimum effectiveness levels for new cancer medicines, managed entry agreements, multicriteria decision analyses (MCDAs), differential/tiered pricing, fair pricing models, amortization models as well as de-linkage models. We are likely to see a growth in alternative pricing deliberations in view of ongoing challenges. These include the considerable number of new oncology medicines in development including new gene therapies, new oncology medicines being launched with uncertainty regarding their value, and continued high prices coupled with the extent of confidential discounts for reimbursement. However, balanced against the need for new cancer medicines. This will lead to greater scrutiny over the prices of patent oncology medicines as more standard medicines lose their patent, calls for greater transparency as well as new models including amortization models. We will be monitoring these developments.

Trends in opioid prescribing in Estonia (2011-2017).

Our objective was to examine the trends and variation in opioid prescribing in Estonia from 2011 to 2017. This retrospective cross-sectional study is based on a nationwide prescription medicines database. We stratified the analysis by treatment indication (cancer vs noncancer pain). Between 2011 and 2017, annual opioid prescribing rates increased by 67% (from 82.9 to 138.6 prescriptions per 1000 population). The annual number of prescriptions per patient did not change substantially (from 2.94 in 2011 to 2.87 in 2017), and was higher among cancer patients (5.07 vs 2.67 annual prescriptions per cancer and noncancer patients, respectively, in 2017). The use of the most potent opioids (morphine, fentanyl) was higher in noncancer than in cancer patients. The use of prescription opioids is low, and raises concern about the potential undertreatment of cancer pain, in parallel with misuse of opioids for either noncancer pain or diversion.

Valproic acid prescription trends among females of childbearing age in Estonia: A 14-year nationwide prescription database study.

PURPOSE: Valproic acid (VPA) is a widely used anticonvulsant that is effective against most seizure types. Due to its teratogenic effects, its use should be avoided among females of childbearing age, unless other treatments are ineffective or not tolerated. This study aimed to determine the prevalence of VPA use in 2005-2018 in Estonia, with special attention to females of childbearing age. METHODS: In this retrospective nationwide population-based cohort study, outpatient prescription data from the national health insurance provider were used. Annual sex- and age-specific prevalence rates were calculated, and changes therein during the study period were evaluated. RESULTS: The annual rates of VPA use among females of childbearing age increased significantly in 2005-2014. After 2014, the increasing trend stopped; in 2014-2018, the prevalence rates declined slightly [prevalence rate ratio (PRR), 0.94; P = 0.136]. In males of the same age, the increasing trend continued (PRR, 1.08: P = 0.028). Among neurologists, the rate of VPA prescription to females aged <15 and 15-44 years decreased during 2014-2018 (PRR, 0.74; P < 0.001 and PRR 0.72; P < 0.001, respectively); no change in prescription frequency was seen among psychiatrists during this period. CONCLUSIONS: The increasing trend in VPA usage among females of childbearing age in Estonia stopped after 2014, when the European Medicines Agency's strengthened restrictions on VPA use in females were communicated extensively in Estonia. The level of awareness of VPA's harmful effects during pregnancy is lower in the psychiatric community.

Comparison of psychotropic medication use in the Baltic countries.

Purpose: While the pivotal role of pharmacotherapy in psychiatry is universal, significant regional differences exist in drug use patterns. Herewith we compare the use of ATC psychotropic drugs (N05, psycholeptics and N06A, antidepressants) in 2010-2015 in the three Baltic Countries with reference to the Nordic Countries.Methods: Data were obtained from the national authorities on medicines as expressed in DDD per 1000 inhabitants per day. A semi-structured questionnaire was used for expert statements on the rationale of current use of medicines.Results: During the observation period the use of antipsychotics, anxiolytics, hypnotics and sedatives, and antidepressants steadily increased, while the growth in use of anxiolytics stagnated in the more recent years. Antipsychotic use was the largest in Lithuania and the lowest in Estonia. The use on anxiolytics in Lithuania was more than twice of that in Estonia and Latvia. Conversely, the use of hypnotics and sedatives was about three times higher in Estonia than in Latvia or Lithuania. Antidepressant use was dominated by the selective serotonin reuptake inhibitors in all three countries, but overall was much lower in Latvia as compared to Lithuania and Estonia. As compared to the Nordic Countries in 2015, antidepressants are used at much lower level throughout Baltics, probably reflecting underdiagnostics of depression and anxiety disorders.Conclusion: While the health-care expenditures in Estonia, Latvia and Lithuania are largely similar, as is the cultural and recent political background of these EU member countries, the extent and the pattern of psychotropic drug use is remarkably variable.

The Expiry of Humira® Market Exclusivity and the Entry of Adalimumab Biosimilars in Europe: An Overview of Pricing and National Policy Measures.

Background: From October 2018, adalimumab biosimilars could enter the European market. However, in some countries, such as Netherlands, high discounts reported for the originator product may have influenced biosimilar entry. Objectives: The aim of this paper is to provide a European overview of (list) prices of originator adalimumab, before and after loss of exclusivity; to report changes in the reimbursement status of adalimumab products; and discuss relevant policy measures. Methods: Experts in European countries received a survey consisting of three parts: 1) general financing/co-payment of medicines, 2) reimbursement status and prices of originator adalimumab, and availability of biosimilars, and 3) policy measures related to the use of adalimumab. Results: In May 2019, adalimumab biosimilars were available in 24 of the 30 countries surveyed. Following introduction of adalimumab biosimilars, a number of countries have made changes in relation to the reimbursement status of adalimumab products. Originator adalimumab list prices varied between countries by a factor of 2.8 before and 4.1 after loss of exclusivity. Overall, list prices of originator adalimumab decreased after loss of exclusivity, although for 13 countries list prices were unchanged. When reported, discounts/rebates on originator adalimumab after loss of exclusivity ranged from 0% to approximately 26% (Romania), 60% (Poland), 80% (Denmark, Italy, Norway), and 80-90% (Netherlands), leading to actual prices per pen or syringe between €412 (Finland) and €50 - €99 (Netherlands). To leverage competition following entry of biosimilar adalimumab, only a few countries adopted measures specifically for adalimumab in addition to general policies regarding biosimilars. In some countries, a strategy was implemented even before loss of exclusivity (Denmark, Scotland), while others did not report specific measures. Conclusion: Even though originator adalimumab is the highest selling product in the world, few countries have implemented specific policies and practices for (biosimilar) adalimumab. Countries with biosimilars on the market seem to have competition lowering list or actual prices. Reported discounts varied widely between countries.

Proposal for a regulation on health technology assessment in Europe - opinions of policy makers, payers and academics from the field of HTA.

INTRODUCTION: In January 2018 the European Commission published a Proposal for a Regulation on Health Technology Assessment (HTA): 'Proposal for a Regulation on health technology assessment and amending Directive 2011/24/EU'. A number of stakeholders, including some Member States, welcomed this initiative as it was considered to improve collaboration, reduce duplication and improve efficiency. There were however a number of concerns including its legal basis, the establishment of a single managing authority, the preservation of national jurisdiction over HTA decision-making and the voluntary/mandatory uptake of joint assessments by Member States. Areas covered: This paper presents the consolidated views and considerations on the original Proposal as set by the European Commission of a number of policy makers, payers, experts from pricing and reimbursement authorities and academics from across Europe. Expert commentary: The Proposal has since been extensively discussed at Council and while good progress has been achieved, there are still divergent positions. The European Parliament gave a number of recommendations for amendments. If the Proposal is approved, it is important that a balanced, improved outcome is achieved for all stakeholders. If not approved, the extensive contribution and progress attained should be sustained and preserved, and the best alternative solutions found.

Barriers for Access to New Medicines: Searching for the Balance Between Rising Costs and Limited Budgets.

Introduction: There is continued unmet medical need for new medicines across countries especially for cancer, immunological diseases, and orphan diseases. However, there are growing challenges with funding new medicines at ever increasing prices along with funding increased medicine volumes with the growth in both infectious diseases and non-communicable diseases across countries. This has resulted in the development of new models to better manage the entry of new medicines, new financial models being postulated to finance new medicines as well as strategies to improve prescribing efficiency. However, more needs to be done. Consequently, the primary aim of this paper is to consider potential ways to optimize the use of new medicines balancing rising costs with increasing budgetary pressures to stimulate debate especially from a payer perspective. Methods: A narrative review of pharmaceutical policies and implications, as well as possible developments, based on key publications and initiatives known to the co-authors principally from a health authority perspective. Results: A number of initiatives and approaches have been identified including new models to better manage the entry of new medicines based on three pillars (pre-, peri-, and post-launch activities). Within this, we see the growing role of horizon scanning activities starting up to 36 months before launch, managed entry agreements and post launch follow-up. It is also likely there will be greater scrutiny over the effectiveness and value of new cancer medicines given ever increasing prices. This could include establishing minimum effectiveness targets for premium pricing along with re-evaluating prices as more medicines for cancer lose their patent. There will also be a greater involvement of patients especially with orphan diseases. New initiatives could include a greater role of multicriteria decision analysis, as well as looking at the potential for de-linking research and development from commercial activities to enhance affordability. Conclusion: There are a number of ongoing activities across countries to try and fund new valued medicines whilst attaining or maintaining universal healthcare. Such activities will grow with increasing resource pressures and continued unmet need.

Compliance with Pregnancy Prevention Recommendations for Isotretinoin in Estonia in 2012-2016.

BACKGROUND: Isotretinoin is an effective treatment for severe acne; no alternative treatment has an equal therapeutic effect. The teratogenic effects of isotretinoin can be avoided, and numerous recommendations and regulations are in force to minimize the risk of pregnancy during treatment. OBJECTIVES: To describe isotretinoin prescription patterns for women aged 15-45 years, assess the concomitancy of isotretinoin and contraceptive use, and determine the rate of potential isotretinoin-exposed pregnancies in Estonia. METHODS: This retrospective, nationwide, population-based, cohort study derived data from national health insurance databases and included female patients aged 15-45 years in Estonia for whom one or more prescriptions for isotretinoin were dispensed between 2012 and 2016. The main outcome was the proportion of women who used systemic isotretinoin and had a concomitant record of (hormonal or intrauterine) contraception use covering the isotretinoin treatment period when pregnancy is contraindicated. RESULTS: Of the 2792 women aged 15-45 years filling an isotretinoin prescription, 15.7% (95% CI 14.4-17.1) had full and 13.9% (95% CI 12.7-15.3) partial (not covering the whole period during which pregnancy is contraindicated) contraceptive coverage. The risk for potential isotretinoin-exposed pregnancy was 3.6 (95% CI 2.0-7.0) per 1000 treated women over the 5-year observation period. The odds for full coverage with effective contraception increased with the age of the patient, with the duration of isotretinoin treatment and over the period of observation. CONCLUSION: Our study adds to the existing literature documenting limited compliance with pregnancy prevention programs for isotretinoin-containing products, and calls for program assessment to identify whether new measures should be taken or whether weaknesses in policy or implementation can be corrected.

Use of a national database as a tool to identify primary medication non-adherence: The Estonian ePrescription system.

BACKGROUND: Medication adherence can be divided into primary and secondary adherence. Primary medication non-adherence (PMN) occurs when a patient does not obtain medicine with their initial prescription. Secondary non-adherence measures prescription refills among patients who previously filled their first prescription. While secondary non-adherence has been studied thoroughly, PMN has been assessed less extensively, due to lack of available data. Estonian ePrescription system might prove a valuable tool for this. OBJECTIVES: The aim of this study was to evaluate PMN and the interval between prescribing and dispensing of medicines using the Estonian ePrescriptions database to establish its potential use for this purpose and for other qualitative drug utilization research measures. Osteoporosis medicines were used as an example. METHODS: The Estonian Prescription Centre was used to evaluate if patients purchase medicines after initial prescription of osteoporosis medicine. Prescriptions from 2012 to 2015 of all patients over 18 were included. PMN was defined as the first prescription not being dispensed before it expired (60 days). The rate of PMN was calculated. RESULTS: Estonian ePrescription System enabled fast evaluation of PMN of osteoporosis patients based on data about prescribing, dispensing and time intervals in-between. Of patients who started osteoporosis treatment 13.1% were primary non-adherent. Of primary non-adherent patients 42% still started treatment at some point during the study. Of patients who did purchase their first prescription 80.4% did so within a week and 95% within 25 days. CONCLUSION: The Estonian ePrescription system is a useful tool for monitoring PMN. The PMN of osteoporosis medicines was identified as lower than previously reported. More similar type of studies about other groups of medicines would be needed to understand the pattern of PMN and give valuable information to healthcare specialists about how to increase initiation of treatment.

Policies for biosimilar uptake in Europe: An overview.

BACKGROUND: Across European countries, differences exist in biosimilar policies, leading to variations in uptake of biosimilars and divergences in savings all over Europe. OBJECTIVES: The aim of this article is to provide an overview of different initiatives and policies that may influence the uptake of biosimilars in different European countries. Recommendations will be formulated on how to create sustainable uptake. METHODS: An overview of policies on biosimilars was obtained via a questionnaire, supplemented with relevant articles. Topics were organized in five themes: availability, pricing, reimbursement, demand-side policies, and recommendations to enhance uptake. RESULTS: In all countries studied, biological medicines are available. Restrictions are mainly dependent on local organization of the healthcare system. Countries are willing to include biosimilars for reimbursement, but for commercial reasons they are not always marketed. In two thirds of countries, originator and biosimilar products may be subjected to internal reference pricing systems. Few countries have implemented specific incentives targeting physicians. Several countries are implementing pharmacist substitution; however, the scope and rules governing such substitution tend to vary between these countries. Reported educational policies tend to target primarily physicians, whereas fewer initiatives were reported for patients. Recommendations as proposed by the different country experts ranged from the need for information and communication on biosimilars to competitive pricing, more support for switching and guidance on substitution. CONCLUSIONS: Most countries have put in place specific supply-side policies for promoting access to biosimilars. To supplement these measures, we propose that investments should be made to clearly communicate on biosimilars and educate stakeholders. Especially physicians need to be informed on the entry and use of biosimilars in order to create trust. When physicians are well-informed on the treatment options, further incentives should be offered to prescribe biosimilars. Gainsharing can be used as an incentive to prescribe, dispense or use biosimilars. This approach, in combination with binding quota, may support a sustainable biosimilar market.

Adaptive Pathways: Possible Next Steps for Payers in Preparation for Their Potential Implementation.

Medicines receiving a conditional marketing authorization through Medicines Adaptive Pathways to Patients (MAPPs) will be a challenge for payers. The "introduction" of MAPPs is already seen by the European Medicines Agency (EMA) as a fait accompli, with payers not consulted or involved. However, once medicines are approved through MAPPs, they will be evaluated for funding by payers through different activities. These include Health Technology Assessment (HTA) with often immature clinical data and high uncertainty, financial considerations, and negotiations through different types of agreements, which can require monitoring post launch. Payers have experience with new medicines approved through conditional approval, and the fact that MAPPs present additional challenges is a concern from their perspective. There may be some activities where payers can collaborate. The final decisions on whether to reimburse a new medicine via MAPPs will have more variation than for medicines licensed via conventional processes. This is due not only to increasing uncertainty associated with medicines authorized through MAPPs but also differences in legal frameworks between member states. Moreover, if the financial and side-effect burden from the period of conditional approval until granting full marketing authorization is shifted to the post-authorization phase, payers may have to bear such burdens. Collection of robust data during routine clinical use is challenging along with high prices for new medicines during data collection. This paper presents the concept of MAPPs and possible challenges. Concerns and potential ways forward are discussed and a number of recommendations are presented from the perspective of payers.

Adherence to osteoporosis medicines in Estonia-a comprehensive 15-year retrospective prescriptions database study.

Some patients do not take medicines as they are supposed to. Our research showed that in Estonia, one fifth of patients did not start treatment with osteoporosis medicines and only 20% used the medicines for at least 3 years as they should. This induces unnecessary costs to the healthcare system. PURPOSE: Medication non-adherence is the number one reason for not obtaining the expected clinical effect of medicines. With osteoporosis treatment, it has been shown that both implementation of treatment and persistence influence the risk of fractures significantly. Long-term adherence to medication in Estonia is to be determined with this study. METHODS: A 15-year retrospective study was carried out in order to establish initiation, implementation, and persistence of Estonian patients. All new users of osteoporosis medicines were analyzed for all prescriptions they received during the study period. Sufficient adherence to treatment was defined as a patient being dispensed 80% or more prescribed doses for at least 1 year. RESULTS: The study period was from 2001 to 2015. Patients (24,652) were included in the study. Of the patients, 93.7% (n = 23,091) were women and 6.3% (n = 1564) were men. Eighteen percent (4636) were dispensed only one prescription. Of the patients, 44.2% included in the study had medication possession ratio (MPR) ≥80% over follow-up period; 8922 (36.2%) who were prescribed from 2001 to 2015 persisted for 1 year with MPR ≥80% and 19.8% persisted for 3 years. Forty percent of expenditure on osteoporosis medication was made for treatment courses with insufficient adherence. CONCLUSIONS: There is room for improvement in Estonia with medication adherence relating to all three aspects that determine adherence-initiation, implementation, and persistence. This means further efforts are to be made to educate patients and healthcare professionals on realizing the importance of good adherence.

Trends in and relation between hip fracture incidence and osteoporosis medication utilization and prices in Estonia in 2004-2015.

Osteoporosis medicines reduce osteoporotic fractures. There is a very strong negative correlation between the consumption of medicines and the price of an average daily dose indicating that affordability is a key factor that could increase consumption of antiosteoporotic medicines and, through that, reduce fractures. PURPOSE: Osteoporosis is a major cause of morbidity and mortality in the modern world. Our study aims to describe the trends in incidence of hip fractures in relation to drug utilization patterns and the average price of antiosteoporotic medicines in Estonia. METHODS: Data on hip fractures was obtained from the medical claims database of Estonian Health Insurance Fund (EHIF). Consumption and price data was obtained from the Estonian State Agency of Medicines (SAM).Consumption is presented using WHO defined daily doses methodology, and the prices reflect the average wholesale price of medicines. RESULTS: From 2004 to 2010 there was a non-significant increasing trend in standardized hip fracture incidence in Estonia, but from 2010 to 2015, the trend turned to a significant decrease of 4.5% per year. The consumption of osteoporosis medication increased significantly from 2004 to 2009 by yearly average of 41.2%. After 2009, the consumption levelled. On contrast, the average price of one daily dose of osteoporosis medication decreased significantly from 2004 to 2009 by 16.9% per year and the decrease also levelled after 2009. This gives a very strong negative correlation of -0.93 (p < 0.001) between the consumption of antiosteoporotic medication and the average price of a daily dose of medication during the study period. CONCLUSIONS: The statistically significant decline of standardized incidence of hip fractures from 2010 onward could at least in part be the result of the high increase in consumption of antiosteoporotic medicines which in turn is strongly negatively correlated with the average price of osteoporosis medicines.