Introduction: There are increasing concerns world-wide with growing rates of antibiotic resistance necessitating urgent action. There have been a number of initiatives in the Republic of Srpska in recent years to address this and improve rational antibiotic prescribing and dispensing despite limited resources to fund multiple initiatives. Objective: Analyse antibiotic utilization patterns in the Republic of Srpska following these multiple initiatives as a basis for developing future programmes in the Republic if needed. Methods: Observational retrospective study of total outpatient antibiotic utilization from 2010 to 2015, based on data obtained from the Public Health Institute, alongside documentation of ongoing initiatives to influence utilization. The quality of antibiotic utilization principally assessed according to ESAC, ECDC, and WHO quality indicators and DU 90% (the drug utilization 90%) profile as well as vs. neighboring countries. Results: Following multiple initiatives, antibiotic utilization remained relatively stable in the Republic at 15.6 to 18.4 DIDs, with a decreasing trend in recent years, with rates comparable or lower than neighboring countries. Amoxicillin and the penicillins accounted for 29–40 and 50% of total utilization, respectively. Overall, limited utilization of co-amoxiclav (7–11%), cephalosporins, macrolides, and quinolones, as well as low use of third and fourth generation cephalosporins vs. first and second cephalosporins. However, increasing utilization of co-amoxiclav and azithromycin, as well as higher rates of quinolone utilization compared to some countries, was seen. Conclusions: Multiple interventions in the Republic of Srpska in recent years have resulted in one of the lowest utilization of antibiotics when compared with similar countries, acting as an exemplar to others. However, there are some concerns with current utilization of co-amoxiclav and azithromycin which are being addressed. This will be the subject of future research activities.

Drug shortages have been identified as a public health problem in an increasing number of countries. This can negatively impact on the quality and efficiency of patient care, as well as contribute to increases in the cost of treatment and the workload of health care providers. Shortages also raise ethical and political issues. The scientific evidence on drug shortages is still scarce, but many lessons can be drawn from cross-country analyses. The objective of this study was to characterize, compare, and evaluate the current systemic measures and legislative and organizational frameworks aimed at preventing or mitigating drug shortages within health care systems across a range of European and Western Asian countries. The study design was retrospective, cross-sectional, descriptive, and observational. Information was gathered through a survey distributed among senior personnel from ministries of health, state medicines agencies, local health authorities, other health or pharmaceutical pricing and reimbursement authorities, health insurance companies and academic institutions, with knowledge of the pharmaceutical markets in the 28 countries studied. Our study found that formal definitions of drug shortages currently exist in only a few countries. The characteristics of drug shortages, including their assortment, duration, frequency, and dynamics, were found to be variable and sometimes difficult to assess. Numerous information hubs were identified. Providing public access to information on drug shortages to the maximum possible extent is a prerequisite for performing more advanced studies on the problem and identifying solutions. Imposing public service obligations, providing the formal possibility to prescribe unlicensed medicines, and temporary bans on parallel exports are widespread measures. A positive finding of our study was the identification of numerous bottom-up initiatives and organizational frameworks aimed at preventing or mitigating drug shortages. The experiences and lessons drawn from these initiatives should be carefully evaluated, monitored, and presented to a wider international audience for careful appraisal. To be able to find solutions to the problem of drug shortages, there is an urgent need to develop a set of agreed definitions for drug shortages, as well as methodologies for their evaluation and monitoring. This is being progressed.

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.

Objective: Irrational use of antimicrobials is a major driver of antimicrobial resistance, exacerbated by dispensing antibiotics without a prescription. Our previous study suggested this was a problem in the Republic of Srpska despite legislation. Since then, a number of activities have been initiated. Consequently, the study aimed to ascertain whether these multiple initiatives had reduced this. Methods: Patients visiting all community pharmacies in the Republic from October 2014 to July 2015 presenting with symptoms typical of an acute, viral and mostly uncomplicated upper respiratory tract infection, with results compared to the previous study. If an antibiotic was suggested, the maximum allowance was Euro 3/ pack. Findings: Self-medication with antibiotics significantly decreased from 58% to 18.5% of pharmacies. In both studies, most patients were offered over-the-counter medication. The most common reason for not dispensing an antibiotic was ‘antibiotics can be dispensed with a prescription only’. The penicillins were the most dispensed antibiotic. Fewer patients than the previous study were given instructions about antibiotic use and no discussion on their side-effects. Conclusion: Whilst encouraging that self-medication decreased significantly, 18.5% was disappointing given recent initiatives Fewer instructions about antibiotics if an antibiotic was dispensed was also disappointing. This suggests the need for even stronger enforcement of the laws as well as further training of pharmacy personnel to ensure future appropriate use of medicines.

Objective: Irrational use of antimicrobials is a major driver of antimicrobial resistance, exacerbated by dispensing antibiotics without a prescription. Our previous study suggested this was a problem in the Republic of Srpska despite legislation. Since then, a number of activities have been initiated. Consequently, the study aimed to ascertain whether these multiple initiatives had reduced this. Methods: Patients visiting all community pharmacies in the Republic from October 2014 to July 2015 presenting with symptoms typical of an acute, viral, and mostly uncomplicated upper respiratory tract infection, with results compared to the previous study. If an antibiotic was suggested, the maximum allowance was €3/pack. Findings: Self-medication with antibiotics significantly decreased from 58% to 18.5% of pharmacies. In both studies, most patients were offered over-the-counter medication. The most common reason for not dispensing an antibiotic was “antibiotics can be dispensed with a prescription only.” The penicillins were the most dispensed antibiotic. Fewer patients than the previous study were given instructions about antibiotic use and no discussion on their side effects. Conclusion: While encouraging that self-medication decreased significantly, 18.5% were disappointing given recent initiatives. Fewer instructions about antibiotics if an antibiotic was dispensed were also disappointing. This suggests the need for even stronger enforcement of the laws as well as further training of pharmacy personnel to ensure the future appropriate use of medicines.

Payers are a major stakeholder in any considerations and initiatives concerning adaptive licensing of new medicinal products, also referred to as Medicines Adaptive Pathways to patients (MAPPs). Firstly, the scope and necessity of MAPPs need further scrutiny, especially with regard to the definition of unmet need. Conditional approval pathways already exist for new medicines for seriously debilitating or life-threatening diseases and only a limited number of new medicines are innovative. Secondly, MAPPs will result in new medicines on the market with limited evidence about their effectiveness and safety. Additional data are to be collected after approval. Consequently, adaptive pathways may increase the risk of exposing patients to ineffective or unsafe medicines. We have already seen medicines approved conventionally that subsequently proved ineffective or unsafe amongst a wider, more co-morbid population as well as medicines that could have been considered for approval under MAPPs but subsequently proved ineffective or unsafe in Phase III trials and were never licensed. Thirdly, MAPPs also put high demands on payers. Routine collection of patient level data is difficult with high transaction costs. It is not clear who will fund these. Other challenges for payers include shifts in the risk governance framework, implications for evaluation and HTA, increased complexity of setting prices, difficulty with ensuring equity in the allocation of resources, definition of responsibility and liability and implementation of stratified use. Exit strategies also need to be agreed in advance, including price reductions, rebates, or reimbursement withdrawals when price premiums are not justified. These issues and concerns will be discussed in detail including potential ways forward.

ABSTRACT The prescribing of medicines is a fundamental component of care for the elderly; however, there is increasing concern with polypharmacy and its impact on morbidity, mortality and costs. As a result, long-term prescription-medicine use and the prevalence of polypharmacy in the elderly in the Republic of Srpska were analyzed. The findings were subsequently used to suggest potential future measures. A retrospective study of all elderly patients during 2005–2010 stratified by age group (three groups), sex and long-term medicine use was performed. Polypharmacy (five or more medicines) increased from 1.4% of the elderly taking medicines long-term to 3.6% by 2010, with 53.6% of elderly taking two or more medicines long-term. The most prevalent diseases were cardiovascular diseases and diabetes. Most prescriptions were in accordance with recent guidelines; however, there was a concern with appreciable prescribing of digoxin and aminophylline. Whilst polypharmacy rates are low in the Republic, the increasing rate is a concern. Further studies are planned.

Background: Infection with the Hepatitis C Virus (HCV) is a widespread transmittable disease with a diagnosed prevalence of 2.0%. Fortunately, it is now curable in most patients. Sales of medicines to treat HCV infection grew 2.7% per year between 2004 and 2011, enhanced by the launch of the protease inhibitors (PIs) boceprevir (BCV) and telaprevir (TVR) in addition to ribavirin and pegylated interferon (pegIFN). Costs will continue to rise with new treatments including sofosbuvir, which now include interferon free regimens. Objective: Assess the uptake of BCV and TVR across Europe from a health authority perspective to offer future guidance on dealing with new high cost medicines. Methods: Cross-sectional descriptive study of medicines to treat HCV (pegIFN, ribavirin, BCV and TVR) among European countries from 2008 to 2013. Utilization measured in defined daily doses (DDDs)/1000 patients/quarter (DIQs) and expenditure in Euros/DDD. Health authority activities to influence treatments categorized using the 4E methodology (Education, Engineering, Economics and Enforcement). Results: Similar uptake of BCV and TVR among European countries and regions, ranging from 0.5 DIQ in Denmark, Netherlands and Slovenia to 1.5 DIQ in Tayside and Catalonia in 2013. However, different utilization of the new PIs vs. ribavirin indicates differences in dual vs. triple therapy, which is down to factors including physician preference and genotypes. Reimbursed prices for BCV and TVR were comparable across countries. Conclusion: There was reasonable consistency in the utilization of BCV and TVR among European countries in comparison with other high priced medicines. This may reflect the social demand to limit the transmission of HCV. However, the situation is changing with new curative medicines for HCV genotype 1 (GT1) with potentially an appreciable budget impact. These concerns have resulted in different prices across countries, with their impact on budgets and patient outcomes monitored in the future to provide additional guidance.

BACKGROUND/AIM Prescription of drugs is a fundamental care component of the elderly. Elderly patients often take multiple drugs, and it is known that polypharmacy may lead to drug interactions and adverse events. The aim of this study was to analyze the long-term drug use and the prevalence of polypharmacy among the elderly population in the Republic of Srpska, Bosnia and Herzegovina. METHODS; A retrospective study of outpatient drug use in 2005 and 2010 was conducted, analyzing prescriptions for patients aged ≥ 65 years reimbursed by the Health Insurance Fund. The study population was stratified by gender and age. Long-term drug use was defined as continuous drug dispensing for a whole year or at least two thirds of the year. Polypharmacy was defined as the use of 5 or more different reimbursed drugs. RESULTS Of all insured people aged ≥ 65 years, long-term drug use was identified in 10% (2005) and in 19% (2010), of whom 62% were women. Two to four different drugs were used by almost 49% (2005) and 54% (2010) of the elderly patients. The polypharmacy prevalence increased from 1.4% (2005) to 3.6% (2010); it increased in all the age groups of both genders. The largest increase was observed in the age group 65-74 years. Polypharmacy prevalence increase was higher in women. The most commonly used drugs were those for to treatment of cardiovascular diseases, in particular drugs for hypertension and cardiac treatment. CONCLUSION The study findings point out to the increase of elderly population with a long-term drug use. Over a half of elderly patients use 2-4 different drugs on the long-term basis. The polypharmacy prevalence was low. It increased in the period of 5 years in both genders. The increase was more prominent in women of all the age groups. The use of multiple drugs and polypharmacy increased with ageing.

Introduction. Antimicrobial resistance is a very serious public health threat worldwide. The main cause of antimicrobial resistance is irrational use of antimicrobial drugs. The goal of the article is to analyze data on outpatient antibiotic consumption in the Republic of Srpska during the period from 2009 to 2014, to present outpatient consumption of the fi rst six antibiotics (the fi fth level of the ATC classifi cation), and, fi nally, to compare the antibiotic use in Republic of Srpska in relation to the antibiotic use in European Union countries. Materials and Methods. Collection and analysis of data on drug consumption is done using ATC/DDD methodology, established by the WHO. Data are taken from the report on drug consumption and distribution in the Republic of Srpska during the period from 2009 to 2014, which are based on submitted data from pharmacies registered in the Republic of Srpska. Results. Results on outpatient antibiotic consumption in the Republic of Srpska, during the period from 2009 to 2014, indicate a total decrease by 3.41 DDDs/1000 inhabitants/day, with the exception of 2010 and 2013, when the antibiotic consumption was increased. In 2014, total outpatient antibiotic consumption in the Republic of Srpska was 31.2% lower than the average consumption in the European Union. During the period from 2010 to 2014, the European Union had a signifi cant increase in antibiotic consumption, while antibiotic consumption in the Republic of Srpska had a tendency of falling. Conclusion. Presented results show a quantitative analysis of antibiotic consumption and provide insight into the outpatient use of antibiotics in the Republic of Srpska, and can be used for further pharmacoepidemiological analysis of antibiotic consumption, which would give a better insight into the therapeutic practice, with the aim of improving the rational pharmacotherapy in the Republic of Srpska. Keywords: antibiotics, outpatient consumption, DDD/1000 inhabitants/day (Scr Med 2016:47:47-52) + , . / 0 1 / 2 3 4 3 5 6 7 8 7 1 7 6 1 9 1 / : 1 0 2 ; < = . : / 3 1 > > ? @ A 4 1 : B 9 C D E F G H I 8 C 7 G H J K L 0 0 A 5 L 0 / @ M = N O P I I 1 B I Q P < . 3 4 0 > 4 0 @ 48 Scripta Medica Vol. 47 • No 1 • April 2016. • www.scriptamedica.com Introduction R S T U V W X Y Z T [ \ Y ] ^ _ ` V a V Y ` V X W V W Y _ T Y ] ` S T b [ T ^ ` T W ` U V W X Y Z c T [ V T W V _ ` S T S V W ` Y [ \ Y ] d S ^ [ e ^ X Y ` S T [ ^ d \ f g _ ] ^ X ` h ` S ^ _ i W ` Y ` S ^ ` U V W X Y Z T [ \ h ` S T T T X ` V Z T X Y _ ` [ Y j Y ] V _ ] T X ` V Y k W U V W T ^ W T W h l S V X S l ^ W ` S T j T ^ U V _ b X ^ k W T Y ] e Y [ a V U V ` \ ^ _ U e Y [ ` ^ j V ` \ V _ S k e ^ _ S V W ` Y [ \ h l ^ W T _ ^ a j T U f m Y l T Z T [ h ` S T U V W X Y Z T [ \ Y ] ^ _ ` V a V Y ` V X W l ^ W Z T [ \ W Y Y _ ] Y j j Y l T U a \ ` S T Y X X k [ [ T _ X T Y ] [ T W V W ` ^ _ X T Y ] W Y e T a ^ X ` T [ V ^ W ` [ ^ V _ W f n _ ] Y [ ` k _ ^ ` T j \ h U k T ` Y ` S T b T _ T ` V X e k ` ^ ` V Y _ W Y ] a ^ X ` T [ V ^ ^ _ U [ T W V W ` ^ _ ` b T _ T W ` [ ^ _ W ] T [ W h ` S T T e T [ b T _ X T ^ _ U W d [ T ^ U Y ] ^ _ ` V a V Y ` V X [ T W V W ` ^ _ X T V W [ V W V _ b T Z T _ ` Y U ^ \ f o p q r _ ` V e V X [ Y a V ^ j [ T W V W ` c ^ _ X T ` Y U ^ \ V W ^ Z T [ \ W T [ V Y k W b j Y a ^ j d k a j V X S T ^ j ` S ` S [ T ^ ` ` Y T T X ` V Z T ` [ T ^ ` e T _ ` Y ] V _ ] T X ` V Y k W U V W T ^ W T W h ^ W l T j j ^ W X Y _ U k X ` V _ b _ k e T [ Y k W Y ] ^ e Y U T [ _ e T U V X ^ j d [ Y X T U k [ T W h ^ _ U V ` [ T s k V [ T W ^ e k j ` V c U V W X V d j V _ ^ [ \ ^ X ` V Y _ V _ Y [ U T [ ` Y W k d d [ T W W Y X X k [ [ T _ X T ^ _ U W d [ T ^ U l Y [ j U l V U T f t r X X Y [ U V _ b ` Y U ^ ` ^ ] [ Y e u v v w h V ` V W T W ` V e ^ ` T U ` S ^ ` ^ a Y k ` u x v v v d T Y c d j T U V T T ^ X S \ T ^ [ V _ ` S T y n ^ W ^ [ T W k j ` Y ] V _ ] T X ` V Y _ W X ^ k W T U a \ [ T W V W ` ^ _ ` a ^ X ` T [ V ^ W ` [ ^ V _ W h l S V X S j T ^ U W ` Y ` S T U V [ T X ` ^ _ U V _ U V [ T X ` X Y W ` W Y ] ^ a Y k ` z f x e V j j V Y _ ^ _ _ k ^ j j \ h V _ X j k U V _ b ` S T X Y W ` Y ] U T X [ T ^ W T U d [ Y U k X ` V Z V ` \ ^ _ U V _ X [ T ^ W T U S T ^ j ` S X ^ [ T X Y W ` W f q { | R S T e ^ V _ X ^ k W T Y ] T e T [ b T _ X T ^ _ U W d [ T ^ U Y ] ^ _ ` V a V Y ` V X [ T W V W ` ^ _ X T V W V [ [ ^ ` V Y _ ^ j ^ _ ` V a V Y ` V X k W T f g ] l T ` ^ i T V _ ` Y X Y _ c W V U T [ ^ ` V Y _ ` S ^ ` Z T [ \ ] T l _ T l ^ _ ` V a V Y ` V X W ^ [ T U T Z T j Y d T U a \ d S ^ [ e ^ X T k ` V X ^ j V _ U k W ` [ \ ` Y U ^ \ h ^ _ U T Z T _ l S T _ l T S ^ Z T ^ _ T l ^ _ ` V a V Y ` V X h a ^ X ` T [ V ^ T Z T _ ` k ^ j j \ S ^ Z T ` S T X ^ d ^ a V j V ` \ ` Y U T Z T j Y d [ T W V W ` ^ _ X T h ` S T [ T ] Y [ T h l T X ^ _ X Y _ X j k U T ` S ^ ` ` S T W V ` k ^ ` V Y _ l T ^ [ T ] ^ X V _ b l V ` S V W Z T [ \ W T [ V Y k W h ^ _ U V ` l V j j a T T Z T _ e Y [ T W T [ V Y k W V ] l T U Y _ Y ` [ ^ ` V Y _ ^ j j \ k W T T } V W ` V _ b ^ _ ` V a V Y ` V X W V _ ` S T ] k ` k [ T f ~ g ` V W T W ` V e ^ ` T U ` S ^ ` a \ u v x v h k _ c j T W W l T S ^ Z T T T X ` V Z T ^ _ ` V a V Y ` V X W h ` S T l Y [ j U d Y d k j ^ ` V Y _ l V j j a T [ T U k X T U a \ z z ` Y    e V j j V Y _ d T Y d j T f € {  r X X Y [ U V _ b ` Y ` S T ‚ Y [ j U m T ^ j ` S ƒ [ b ^ _ V „ ^ ` V Y _ h [ ^ ` V Y _ ^ j k W T Y ] U [ k b W e T ^ _ W ` S ^ ` … d ^ ` V T _ ` W [ T X T V Z T e T U V X ^ ` V Y _ W ^ d d [ Y c d [ V ^ ` T ` Y ` S T V [ X j V _ V X ^ j _ T T U W h V _ U Y W T W ` S ^ ` e T T ` ` S T V [ Y l _ V _ U V Z V U k ^ j [ T s k V [ T e T _ ` W h ] Y [ ^ _ ^ U T s k ^ ` T d T [ V Y U Y ] ` V e T h ^ _ U ^ ` ` S T j Y l T W ` X Y W ` ` Y ` S T e ^ _ U ` S T V [ X Y e e k _ V ` \ † ‡ ‚ m ƒ h z w ˆ x ‰ f Š Objectives: z f R Y ^ _ ^ j \ „ T ` S T U ^ ` ^ Y _ Y k ` d ^ ` V T _ ` X Y _ W k e d ` V Y _ Y ] ^ _ ` V V _ ] T X ` V Z T W ] Y [ W \ W ` T e V X k W T ‡ ‹ b [ Y k d ‰ ^ _ U ^ _ ` V a V c Y ` V X W ‡ ‹ v z b [ Y k d ‰ V _ ` S T Œ T d k a j V X Y ]  [ d W i ^ U k [ V _ b ` S T d T [ V Y U ] [ Y e u v v w ` Y u v z  Ž u f R Y W S Y l Y k ` d ^ ` V T _ ` X Y _ W k e d ` V Y _ Y ] ` S T  [ W ` W V } ^ _ ` V c a V Y ` V X W ^ ` ` S T  ] ` S r R  j T Z T j ‡ g ‘ ‘ ‰ d T [ \ T ^ [ Ž ’ f R Y X Y e d ^ [ T Y k ` d ^ ` V T _ ` ^ _ ` V a V Y ` V X X Y _ W k e d ` V Y _ V _ ` S T Œ T d k a j V X Y ]  [ d W i ^ V _ [ T j ^ ` V Y _ ` Y X Y _ W k e d ` V Y _ V _ ` S T y k [ Y d T ^ _ n _ V Y _ f Materials and Methods  Y j j T X ` V Y _ ^ _ U ^ _ ^ j \ W V W Y ] U ^ ` ^ Y _ U [ k b X Y _ W k e d ` V Y _ V W U Y _ T k W V _ b r R  “ ” ” ” e T ` S Y U Y j Y b \ T W ` ^ a j V W S T U a \ ` S T ‚ m ƒ  Y j j ^ a Y [ ^ ` V _ b  T _ ` [ T ] Y [ ” [ k b  ` ^ ` V W ` V X • T ` S Y U Y j c Y b \ V _ ƒ W j Y f R S T ‚ m ƒ b k V U T j V _ T W ^ [ T k W T U ` Y V e d j T e T _ ` ` S T r R  U [ k b X j ^ W W V  X ^ ` V Y _ ‡ r _ ^ ` Y e V X ^ j R S T [ ^ d T k ` V X  S T e V X ^ j  j ^ W W V  X ^ ` V Y _ ‰ ^ _ U ” ” ” W ‡ ” T  _ T U ” ^ V j \ ” Y W c T W ‰ h ^ _ U ` Y e Y _ V ` Y [ ` S T ^ _ _ k ^ j U [ k b X Y _ W k e d ` V Y _ f w h z v • Y _ V ` Y [ V _ b Y ] ^ _ _ k ^ j X Y _ W k e d ` V Y _ V _ ` S T Œ T d k a j V X Y ]  [ d W i ^ V W [ T b k j ^ ` T U a \ _ ^ ` V Y _ ^ j j T b V W j ^ ` V Y _ f o o p o q r R  “ ” ” ” W \ W ` T e V _ X j k U T W ` S T r _ ^ ` Y e V X ^ j R S T [ ^ d T k ` V X  S T e V X ^ j ‡ r R  ‰  j ^ W W V  X ^ ` V Y _ Y ] U [ k b W ^ _ U U T  _ T U U ^ V j \ U Y W T W ‡ ” ” ” W ‰ ^ W ` S T k _ V ` ] Y [ e Y _ V ` Y [ V _ b ` S T k W T Y ] e T U V c X V _ T W V _ ^ b V Z T _ d Y d k j ^ ` V Y _ Y [ S T ^ j ` S V _ W ` V ` k ` V Y _ f r R  V _ X j k U T W X j ^ W W V  X ^ ` V Y _ Y ] ^ X ` V Z T W k a W ` ^ _ X T W V _ U V T [ c T _ ` b [ Y k d W h U T d T _ U V _ b Y _ ` S T Y [ b ^ _ W Y [ W \ W ` T e W Y ] Y [ c b ^ _ W ` Y l S V X S ` S T \ ^ [ T T T X ` V Z T Y _ h ^ _ U ^ X X Y [ U V _ b ` Y ` S T V [ ` S T [ ^ d T k ` V X ^ j h d S ^ [ e ^ X Y j Y b V X ^ j ^ _ U X S T e V X ^ j d [ Y d T [ ` V T W f ” ” ” V W U T  _ T U ^ W ^ W ` ^ ` V W ` V X ^ j k _ V ` Y ] ^ b [ T T U ^ _ U U T ` T [ c e V _ T U ^ e Y k _ ` Y ] ` S T U [ k b ` S ^ ` V W e Y W ` X Y e e Y _ j \ k W T U ] Y [ ` S T e Y W ` X Y e e Y _ V _ U V X ^ ` V Y _ ] Y [ e T ^ W k [ V _ b T } d Y W k [ T Y ] b V Z T _ d Y d k j ^ ` V Y _ ` Y X T [ ` ^ V _ U [ k b W Y [ b [ Y k d W Y ] U [ k b W f ” ” ” V W e Y W ` j \ T } d [ T W W T U ^ W l T V b S ` k _ V ` W ‡ b h e b h b ‰ h ^ _ U V ] ` S V W V W _ Y ` d Y W W V a j T U k T ` Y Z ^ [ V Y k W [ T ^ W Y _ W ‡ ] Y [ T } ^ e c d j T h ` S T X Y e a V _ T U d [ T d ^ [ ^ ` V Y _ W h Z ^ [ V ^ a j \ U Y W ^ b T h T ` X f ‰ h ` S T k _ V ` U Y W T ‡ n ” ‰ Y ] ^ b V Z T _ d S ^ [ e ^ X T k ` V X ^ j U Y W ^ b T k _ V ` ‡ ` ^ a j T ` h X ^ d W k j T h ^ e d Y k j T ‰ V W k W T U f ” ” ” e T ` S Y U Y j Y b \ V W V _ U T d T _ U T _ ` Y ] d [ V X T ^ _ U _ k e a T [ Y ] V _ S ^ a V ` ^ _ ` W h W Y V ` V W W k V ` ^ a j T ] Y [ U T W X [ V a V _ b ^ _ U X Y e d ^ [ V _ b U [ k b k W T Y Z T [ ` V e T h X Y e d ^ [ V W Y _ Y ] d [ T W X [ V a V _ b a T ` l T T _ U V T [ T _ ` b T Y c b [ ^ d S V X ^ j ^ [ T ^ W ^ _ U U V T [ T _ ` S T ^ j ` S ] ^ X V j V ` V T W f R S T [ T ] Y [ T h ` S V W e T ` S Y U V W W k V ` ^ a j T ] Y [ e Y _ V ` Y [ V _ b d S ^ [ e ^ X Y ` S T [ ^ d \ ^ _ U [ ^ ` V Y _ ^ j V „ ^ ` V Y _ Y ] ` S T [ ^ d \ f ” [ k b X Y _ W k e d ` V Y _ V W T } d [ T W W T U ^ W ` S T _ k e a T [ Y ] ” ” ” W d T [ z v v v V _ S ^ a V ` ^ _ ` W d [ T W X [ V a T U ] Y [ Y _ T U ^ \ ‡ ” ” ” W “ z v v v V _ S ^ a V ` ^ _ ` W “ U ^ \ ‰ h ^ _ U V _ S Y W d V ` ^ j W T ` ` V _ b W ^ W ` S T _ k e a T [ Y ] U T  _ T U U ^ V j \ U Y W T W d T [ z v v d ^ ` V T _ ` c U ^ \ W ‡ ” ” ” W “ z v v d ^ ` V T _ ` c U ^ \ W ‰ f – Results R S T ^ _ ^ j \ W V W Y _ U [ k b X Y _ W k e d ` V Y _ V W a ^ W T U Y _ U ^ ` ^ W k a c e V ` ` T U ] [ Y e w ’ f — ˜ Y ] d S ^ [ e ^ X V T W [ T b V W ` T [ T U V _ ` S T Œ T c d k a j V X Y ]  [ d W

The manufacturer of pregabalin has a second use patent covering prescribing for neuropathic pain: its principal indication. The manufacturer has threatened legal action in the UK if generic pregabalin rather than Lyrica is prescribed for this indication. No problems exist for practitioners who prescribe pregabalin for epilepsy or generalized anxiety disorder. This has serious implications for health authorities. In Germany, however, generics could be legally prescribed for any approved indication once one indication loses its patent. We aim to establish the current situation with pregabalin among principally European countries. Personnel from 33 regional and national health authorities mainly from Europe, and nine from universities across Europe working as advisers to health authorities or with insight into their activities, were surveyed regarding four specific questions via email to shed light on the current situation with Lyrica and pregabalin in their country. The information collated from each country was subsequently checked for accuracy with each co-author by email and face-to-face contact and collated into five tables. The scenarios ranged from extending the patent life of Lyrica (e.g. France), endorsing the prescribing of Lyrica for neuropathic pain (e.g. Catalonia and South Korea), and current prescribing of pregabablin for all indications (e.g. Serbia and Germany). Little activity has taken place in European countries in which generic pregabalin is not yet reimbursed. The availability of generic pregabalin has prompted a number of different activities to be undertaken among the 33 countries and regions surveyed. The situation in Serbia and the historic situation in Germany provide examples of ways to maximize savings once a product loses its patent for at least one indication.

Background: There are potential conflicts between authorities and companies to fund new premium priced drugs especially where there are effectiveness, safety and/or budget concerns. Dabigatran, a new oral anticoagulant for the prevention of stroke in patients with non-valvular atrial fibrillation (AF), exemplifies this issue. Whilst new effective treatments are needed, there are issues in the elderly with dabigatran due to variable drug concentrations, no known antidote and dependence on renal elimination. Published studies showed dabigatran to be cost-effective but there are budget concerns given the prevalence of AF. These concerns resulted in extensive activities pre- to post-launch to manage its introduction. Objective: To (i) review authority activities across countries, (ii) use the findings to develop new models to better manage the entry of new drugs, and (iii) review the implications based on post-launch activities. Methodology: (i) Descriptive review and appraisal of activities regarding dabigatran, (ii) development of guidance for key stakeholder groups through an iterative process, (iii) refining guidance following post launch studies. Results: Plethora of activities to manage dabigatran including extensive pre-launch activities, risk sharing arrangements, prescribing restrictions and monitoring of prescribing post launch. Reimbursement has been denied in some countries due to concerns with its budget impact and/or excessive bleeding. Development of a new model and future guidance is proposed to better manage the entry of new drugs, centering on three pillars of pre-, peri-, and post-launch activities. Post-launch activities include increasing use of patient registries to monitor the safety and effectiveness of new drugs in clinical practice. Conclusion: Models for introducing new drugs are essential to optimize their prescribing especially where concerns. Without such models, new drugs may be withdrawn prematurely and/or struggle for funding.