 Sen oedd o'r blynedd yma звod yw'r deimlo. Mae'n rhaid wneud eu bod yn ffơi i brydiol. Roeddwn yn rhaid yn bryd i ffyrdiwyr. Asfyrdiwyr, oswer o bethwyr. Mae'n bryd o ddechrau, mae'n ddweud. Yma yma, dyda'r ddechrau mewn ymwneud am y cerddurol fyddur i'w mwyáu, fod y cerddwyr i'r ddechrau mewn cerddurau o'r deimloiede arfer yn allan. Mae'r meddwl mewn gweliannol, lle mae'n meddwl ei dynnu'n meddwl. Mae'r meddwl mewn gweliannol ar gyfer y gyllid yn... Mae'n meddwl mewn gweliannol ar gyfer y cyflwyllus. Mae'r meddwl yw i'r meddwl yma, sydd wedi'u cyflwyllus cyflwyllus. I'm very happy to introduce Simon Fosier. Thank you very much, Hans, and for the kind introduction. I will certainly report back to my colleagues in Paris, Barcelona, and scatter around Europe about your kind words about Europe. I hope that we'll meet the expectation. My name is Simon. I can see that we are quite close. I took off my jacket because it seems to be quite informal here, so I'm very happy to be here. I'm Italian. I've been working at Eurordis for the past year. As a matter of fact, last Friday was my first anniversary at Eurordis, but I've had ten years of work previously in public health in Brussels. I've spent the last 13 years of my life here in Brussels working in politics, as well as in consultancy, always on public health, public affairs and advocacy. My role within Eurordis is to look on one hand at all European and international developments, so I work a lot in public affairs, advocacy and lobbying on European legislations, such as the current one that is coming in together with my colleagues on health technology assessment, which is going through the European Parliament and the other institution's co-decision process. Plus, I work a lot on all the other access issues, access and affordability, which is one of the topic particularly for orphan products, but in general the affordability of new innovative treatment has been on the agenda for quite some times and it's coming to be, it's a global issue, it's no longer a developing countries issue, but it's a real world issue. So, without further ado, today I will talk a little bit about Eurordis, only very briefly, just to give you a sense if you don't know Eurordis, but given that we are very few, please do interrupt me at any point if there is anything that you want to ask, anything that is not clear, do let me know English, French and Italian, no problem. Dutch might be a little bit difficult as I said, but hey, in that sense. So, from the briefing on from my iPhone, so the idea is to walk you through from the discovery process linked to the regulatory framework and that's linked to access and affordability, because the three in the current environment cannot be taken in isolation, you cannot take the regulatory framework alone, you cannot take the access framework alone, but they need to be all integrated. I hope that with this presentation you understand where we stand in this area. So, then I will look a little bit on the different mechanisms of expanded access, compassionate use, adaptive pathways or adaptive licensing, but also expanded access very briefly. And then in the end I will just summarise a little bit the current challenges, but also opportunities that there are in terms of developing and improving the situation on access and affordability. So, a little bit about Eurordis. Eurordis is quite a large umbrella organisation of rare diseases organisation across Europe and beyond. We have close to 800 organisation affiliated to our umbrella organisation and our structure constituted of individual patient organisation, but also European Federation of rare diseases, take 65 roses for instance, et cetera, et cetera, as well as one of the things that we push now a bit over 20 years of existence is the constitution of national alliances for rare diseases and we have that pretty much in every single country in the European Union. We have 40 plus staff that is based in Paris, Brussels and Barcelona, plus a few others that are working remotely. Flexibility is important in our association so we have people working from Germany, from the UK as well. 40 plus, it works on a number of different issues, particularly around our three key areas of work, which are patient awareness, patient awareness, patient advocacy and patient empowerment. Particularly we have quite a lot of staff working in capacity building, and I wanted to mention it here. We have, on our website, you can see that our Europe is Open Academy, which is all the training that we do through our summer school, winter school and digital programme. The summer school is upcoming in June, so enrollment is closed for quite some time, but it's very, very useful week in Barcelona also in June. Barcelona in June is not bad. It's very much looking at every single aspect of the clinical development process, plus HDAs, plus a lot of other things for the empowerment of the patient community. We have staff working in the regulatory process particularly, therapeutic development, et cetera, et cetera. This because we have many challenges that as a group, as a group of rare disease, individually, as you probably will know, from the myeloma and the subgroups individually, it's very difficult to make a difference. Together, the rare disease community has got pretty much around 30 million people living with the rare disease in Europe only, and about 300 million in the world. Together we should make a much greater difference, because many of the, and probably let me know if these are some of the keywords that you see also in your own individual disease, but the knowledge is, well, first and foremost, patient and experts are scattered geographically, so the travelling of knowledge is always very difficult. Patient are often overall misdiagnosed, undiagnosed, misdiagnosed, and then they wait years for an appropriate treatment. One of the other things that I must add at the moment is that out of the 6,000 rare diseases that are recognised, there are about only 5% that have unauthorised therapy, and we're talking about, not always talking about disease modifying, mostly we're talking about management on the symptoms. The resources in general are limited, reliable information is scarce, and we have lack of treatments and challenges to access adequate care, but probably I'm not saying anything new to you at the moment. So what we're trying to do is a lot actually, that's why we have drawn into a possibly quite a solid organisation as a European Association for Patient Go, because we are acting on so many different issues, and we are fortunate enough that through the work that has been done in the past 20 odd years on rare disease specifically, we have been able to position rare diseases as a public health challenge where there is effectively a European added value. And in times where we live in politically, showing that there is a real European added value in cooperation is very important to us. Today I will talk how we are trying to address access to offer medicinal products and treatment for rare diseases in the second part of the presentation. So what I'm going to start with is particularly an overview of how the clinical development for drugs are connected to the regulatory framework, but also then to the access to treatments. And then I will go a little bit into the more details of the regulatory process at the EMA, particularly for the centralised procedure. Let me know if you know about it, and if I am either saying something that you already know or if I'm saying something that is wrong. You can always challenge me. And then talk later about the access issues. So here you can see what is the typical process at the top from preclinical and discovery phase through to post-marketing surveillance. As you can see, this is particularly valid for small molecules, so classic pharmaceuticals. Development for advanced therapeutic or medicinal products such as gene therapy or cell therapy might be slightly different and even probably even more complicated. So this is a simplification for the purpose of the presentation, but you will see that from the very high number of compounds that are possibly a likely candidate, we arrive at particularly the industry figures that they provide is between 22% and 10% of the compounds that come to clinical trials, so phase one, and then they are approved. So it's a very, very difficult process, and that is also even more problematic in other areas with more complex diseases. So you can see this is very much drug discovery and preclinical phase. It's very much industry academia. In our countries such as the US, I have had the fortune to listen to a couple of association representative from the US into solid tumours areas, Sarkoma and Chrodroma, and in the US very much their foundation are very much also driving drug discovery and the clinical research, whereas in Europe we are, as a patient organisation, we are concentrating on different areas, but that's probably something that we should explore. And then for the clinical trials, the sponsored or academia will push it forward, and then very much from phase two, phase three, usually is the company that brings it forward towards access. Now, what I'm going to talk about specifically on the first part is also what are the incentives of the regulatory framework briefly about pushing for the discovery of treatment for rare conditions such as myeloma, but many others, and then going in particular on what the marketing authorisation process is, then going to the next step, what are the requirements on health technology assessments and pricing and reimbursement negotiations, because that's very much where the black box of access is, why I'm sure you all experience as European organisation, international organisation, that in certain countries their reimbursement comes earlier and in others doesn't come at all. Sometimes the reasoning for the denial is price or affordability. Sometimes, in some other times, the agency is responsible for the assessment to use different type of assessment models and there is one case on Revlimid that we will show later on where the assessment differs from country to country and you will understand why people, patients in some countries will say, well, why I'm not getting the same drug in another country. Then always talking about compassionate use and how we can provide a little bit of respite and try to address the access problems and also from a combination of regulatory and early access, the adaptive pathways and the priority medicine or prime scheme, that is the European Medicines Agency. I'm going to show you a very beautiful slide, very complex, isn't it? Okay, so I'll break it down for you. It is very similar to what I was talking a little bit before but this shows in one single slide is the framework for incentives for drug development across Europe. We're talking about what are the economic incentives, regulatory incentives, data protection incentives that are relevant for drug development. I'll take the case specifically for all-for-medicine but you see that when we were talking before about the number of compounds that are in discovery it drops down dramatically and this is why from the industry point of view particularly there is a need for patents but also other type of regulatory incentives particularly for orphans in terms of market exclusivity. We see specifically at the bottom that we have the process that was specifically developed for orphan medicine or product in 1999-2000 in which very much helped creating the new therapies for rare diseases. If we think that before 2000 there were eight medicinal products approved for rare diseases and up to now we have now 143 medicinal products approved in the shorter space of 117 years. So that's very important and it shows that you might be aware that a lot of the discussion is focused on the high price tag that orphan medicinal products have which is true and not true because in many cases in most cases the medicinal product for rare diseases do cost less than, on average they cost around between 35,000 and 40,000 euro per year which is quite normal. The percentage of orphan drugs that go into the six figures or above 100,000 euro per patient is below 20% so it's a small fraction. Sometimes one of my daily job is to try to dispel the myth that the budget dedicated to orphan drugs is going to completely broke the bank in the pharmaceutical budget or spending. Specifically another example is that overall in Europe 18% of the overall healthcare budget is dedicated to pharmaceuticals and of that 5% is dedicated to orphan medicinal products. 5% of the 18% thinking that that 5% for the moment is going to collapse or driving the collapse of the system is a little bit difficult to understand. There are a number of fears particularly from payers that given the scientific advances that we have and as we are discovering more and more therapies for rare diseases that these 5% will increase and definitely will be a problem. We understand that and thus we are working towards creation of a framework that would help having more therapies at a lower price. So today I'm going to briefly talk about the centralized procedure which is at the European Medicine Agency which is one of the two ways of having a product adaptor but it is actually the only way that innovative therapies can be approved in Europe. By the way, many of these resources are available on the European Medicine Agency website which is very well prepared sometimes a little bit cumbersome to navigate but there is a lot of valuable information that are available on the explanation of the regulatory framework. So you do have two. In many cases the national authorization procedure is still used for some products and for all the products so the mutual recognition and the decentralized procedure are still there but the centralized procedure and I will show a little bit later is the one preferred for rare disease therapies. What is the centralized procedure? The procedure is one marketing authorization application for a whole 28 members. Is there anyone from the UK here? No, well that's going to be a problem for them in the future but still the assurance that we receive is that there is already in place mutual recognition with party countries such as the Norway and Switzerland and so on so in this case the most likely escape way would be this third country recognition. The UK though have been a very important driver of the European Medicine Agency in terms of expertise and knowledge and that will be felt in the future. So the EMA proceeded to the evaluation through a number of different committees and the authorization will be available in all UN member states in all your languages with a number of product information on some of the SMPC, summary of product characteristics, labelling and package leaflet plus a number of obligations that come with the European marketing authorization which includes post authorization studies, surveillance studies, pharmacovigilants, etc. One thing that is causing us some trouble in terms of access for the next phase is that an orphan first designation but certainly for orphan authorization is valid for 28 member states. However, there are 28 different markets with different procedure for pricing and reimbursement. This is the reason why certain countries like Germany which have a free entry at the point of marketing authorization you will see that they have access earlier to certainly for rare diseases but then they still have problems. Others, although theoretically there is in place a directive on transparency of the pricing and reimbursement process this is hardly respected and thus there is still no clarity in terms of how long it would take to have a price of medicine reimbursed and available continuously on the market. So what are the medicines that are mandatory for evaluation at EMA? As you can see, most of the innovative medicine that are coming in will be going through the centralized authorization particularly for rare diseases, cancer, HIV, neurodegenerative and all the main diseases that are also on more complex procedures such as gene therapy, cell therapy, etc. Before I go into the procedure and with a number of acronyms is there any question? This is the overall procedure for human medicine authorization. We have three main phases. One is a price admission phase, the evaluation phase and the post authorization phase. There are a number of different committees that are included and I can provide you with the different acronyms but the key ones that are interesting for our community are the CHMP which is the Committee for Human Medicine and is responsible for all medicine for human for the evaluation of all medicine. The COMP, which is the Committee for All for Medicine of Product, the CUT, the Committee for Advanced Therapeutical Medicine or ATMP, the PDCO, which is the Pediatric Committee and that's it. Then in the price admission phase for the ortho-designation which I'll go a little bit later on which is different from the ortho-medicinal product of authorization, there are activities that are done in the price admission phase at that point when the price admission phase is concluded then the evaluation for a marketing authorization application will start and will have also the evaluation for the CHMP. Once the evaluation is from the CHMP is adopted then is transmitted to the European Commission for final adoption. Included, the marketing authorization is finally granted and is valid in all EU member states. Then there are many post-marketing authorization requirements particularly around pharmacovigilants and in the cases of ortho-medicinal product or certainly all the therapies that have conditional approval the post-marketing authorization phase is really important these days particularly with the increasing importance in the collection of data to ensure that for instance in the case of a conditional approval so done at an earlier phase is important to collect real world data or data generated in clinical practice to make sure that the effectiveness the efficacy and effectiveness and the safety of the product are really happening and then can go back to be to the European Medicine Agency for a full approval. So this is the process of a view overall for the general for the general human medicine procedure at the CHMP as you see the overall process should last no longer than 277 active days there are two opportunities for a stop clock per clock stop per clock stop per clock stop where the procedure officially is stopped and so also the counting towards the 277 day in this particularly at the list of questions and outstanding issues there are possibilities for the companies to ask for a procedure to stop the clock in particular along this timeline the five key areas that are looking at is the evaluation of the benefit and risk the assessment of the risk management plan the assessment on need for post safety and efficacy studies which again for the medicines that are coming in for particularly for rare diseases there is a much greater need because of the condition on which therapists for rare diseases are developed the small number of participants thus the classic data requirements for medicine for more general more prevalent diseases are not possible to be met so we need to have data based on very very small population and thus the continuous evaluation and request for post safety and efficacy studies is much greater also the other two points that are evaluated are the assessment of product information the preparation of the RMP now I am going to talk a little bit about the orphan drug regulatory process because it is a little bit more complicated in the sense that there are two phases one is the granting of an orphan indication and the second part is the granting of the orphan medicinal product authorization the orphan indication is that orphan designation is a pre-submission process that industry sponsors but also SMEs and also academia can access to when they find the potential for a drug candidate to target as more population this will grant a series of incentives for the sponsor in terms of protocol assistance scientific advice, product advice that is available at the European Medicine Agency in view of the preparation of an orphan medicinal product authorization in this case when one moves from the designation to the product authorization phase and there is a different one of the perks of the orphan medicine product is that there is a 10-ears market exclusivity for the product when approved now many critics of this legislation say that 10-ears is too long but what we can say is that an orphan marketing authorization and even the designation is not easy to obtain it's not easy to maintain and it definitely covers a very long period of time I know of industry and of product that I've spent 17 years and just now without having a single product adopted and being spending 17 years of research and development and just now having a product on the market so for these specific therapies and you know that rare diseases are mostly of genetic condition, 80% of them it's very important to have enough time to recoup the investment made in the current and existing framework and as you can see this data from the European Medicine Agency itself we have had a great number of orphan that have received an orphan designation almost 1,700 orphan designation but actually only 10% of them have turned into an orphan medicine product authorization roughly 10% and this is encouraging on one hand in the sense that a lot of science is going into that and we have a lot of better knowledge about certain diseases how products are working etc but on the other hand how do we ensure that those candidates are turning into approved medicine products and that is really something where we need to work towards there are certain regulatory procedures that are helping like adaptive pathways to start having candidates that are likely to arrive to authorization to arrive in the market early on and to gather thanks to better data collection system that we have these days collecting the real world evidence with the real world data that are necessary to confirm the efficacy of the medicine in question so we have talked about the process but now what type of approval can arrive the standard is classic marketing authorization where the full package is complete so the comprehensive data there full marketing authorization is granted the conditional approval which is something that is very frequent in our field is where the comprehensive data are not available and in rare diseases and the population are usually small that some data are not possible to be taken into account I understand the regulators are now a bit more flexible in trying to get different type of data available but it still must fulfill some scopes definitely the conditional approval is only dedicated to orphan drugs, emergency threats and serious life threatening diseases it is not forever but is applicable for one year and renewable and there are also other exceptional circumstances where comprehensive data are not available but must meet specific criteria and rarity and scientific knowledge now any questions so far? have I been clear? Prime which sounds quite more funky but is priority medicine relatively new because it started in 2016 type of approval that the European Medicine Agency has put forward particularly to grant faster access to real innovative therapy so in particular to foster the development of medicine with major public health interest and I believe there is a candidate in there in prime for one specific subset of multiple myeloma carty cell therapy developed by cell gene candidate in prime since November so what is trying to do is three things because of these innovative therapies are coming with we are talking about specific therapies that utilised very complex mechanisms such as carty cells but also gene therapies and so on and so forth there are more scientifically advanced but at the same time a little bit more difficult to assess particularly with regards to their long term effects so what it aims to do is to reinforce the scientific and regulatory advice optimise the development for robust data generation and enable accelerated assessment on something that we as a role this have been to be fair not only us we have been advocating for a long time which is the early dialogue between the regulators the manufacturers, the clinician and the patient to ensure that there is a better understanding of the disease, a faster development of the product and accelerated assessment now at this stage and with the view of the access and affordability questions we are advocating very much also for the addition of the fifth category which is the one of the payers and the evaluators so HDA and competent authorities for pricing and reimbursement this is happening but it's low, very slow because there are still reticences and issues around trust between the different parties the eligibility criteria are very naturally fitting for diseases because it must the candidate for prime eligibility have to have the potential to address to a significant extent which we are talking up to life sorry disease modifying treatments and a medical lead where there are no satisfactory methods existing that brings a major therapeutic advantage or a significant benefit that are introducing new methods or improving existing ones and there are meaningful improvements on efficacy compared to existing product so we are quite awful for this but as in the case of adaptive licensing or adaptive pathways that I will show you a little bit later that brings the access faster because this is a key problem one thing that I did not mention before is that on rare diseases on average the time that is spent between marketing authorization and full access is between 18 and 24 months that is different from having also continuous access through early access program or compassionate use so it's a major problem that is still existing and this is bringing it nicely to me to the next part of the session sorry Hans, we have until 12.30? I think I will have another few minutes on this and then I will be happy to take any other question you might have as I was saying there are at least four key challenges that we see particularly in the orphan disease space in the current system yes there is no decision for marketing authorization or reimbursement for rare disease therapy can take up to 10 years, if not longer more problematic is the fact that once a medicine is approved about a third of the population that would be in Europe eligible for access does not have, we are talking about 30% so that is quite important and then another third only arrive at access only after several years months of waiting and then we have the inequalities that are present between countries East to West in Europe where certain countries and even region within countries do grant approval at different stages just this week looking at a case where in approved medicine for Duchenne muscular disorder in Spain is approved and reimbursed in certain region but one other is not in the UK when we talk about the term of postcode lottery in terms of what type of treatment you can receive the parents of this child with Duchenne consider moving from another to another region just to access the treatment and I personally don't think that this is acceptable but there are difficulties within the system to ensure affordability and that leads me to the fourth point that is the cost now this is possibly true and we see that there are not always prices that are responsibly or responsibly set but the system per se is a bit broken in our view because for rare diseases the European level is the right level to negotiate a price even negotiate price per volume contract but this is not happening because on one end there is a request for confidentiality in terms of the agreement and it's not just about the indices that don't want to disclose the price it's also about the competent authorities that do not want to disclose the price compared to the one that has happening in other countries so it is the system you cannot blame one of the other it's the system that needs to be fixed when you come to assessment for instance that is one of the key problems that has been trying that the current proposal legislative proposal on the table on HTA or health technology assessment at European level should try to fix is that many different assessor use different systems for assessing the same drug and the result is that the same drug has different approval for reimbursement in different countries and even then because reimbursement drugs for specific diseases is always a political decision in many cases a political decision sometimes even this assessment the assessment previously indicated is not followed so there is no transparency system we really hope and we are supportive of this proposal for HTA cooperation in Europe this will bring at least for the clinical value assessment real transparency and real clarity of how the scientific value of the clinical value of a product is assessed throughout Europe to reduce the inequalities that there are because this is an exception that was talking about Revlimid as you can see at the time of reimbursement now I believe the 10 years exclusivity for Revlimid is ended in last year generics will come here generics will come in so there will be potentially savings in the system but not reimbursed in the UK reimbursed conditional with restriction in other four countries and not assessed in France so you see the system is leading to the different inequalities one possible solution is the adaptive pathways which is really clearly one of the ways that you could start the overall dialogue much earlier stage with the involvement of the five key categories of people that need to be involved and should look at in cases of conditional marketing authorization how do you have the data available on how can you connect the data to have available an assessment for a longer period of time and how can you link those data to adaptive pricing and reimbursement criteria so that you can there can be flexible arrangement put in place such as managing agreements but that always needs a multi stakeholder approach Compassionate use here we have published last year a very valuable resource on compassionate use throughout Europe this is a partial response to the issues of access and a partial response that in if every countries would adopt the ATU system in France will be much better practice but that is not the case it's a possibility but a compassionate that takes place prior to registration of a medicine but not all countries benefit from an efficient scheme for compassionate use and still there will be maintaining the differences in access between countries so this is a possibility and in that position paper from a year ago we provided a number of recommendations for policy changes to ensure that compassionate use is taken up better in different countries countries where it works, Italy, Spain may not be the case to change now I don't want to finish on a negative note so what we see as the solution to all the challenges we had before is a collaborative approach between different member states and an even stronger collaborative approach now we have erodus and has pushed but this is a process that stem from a European Commission initiative on the transparency of on the process of corporate responsibility on the pharmaceuticals that is called a mechanism for collaborative coordinated access to all from medicine products voluntary confidential and non binding process that involves patients manufacturers, assessors and payers in the context of the medicine evaluation committee which is a group that groups together different mutualities and payers across Europe so that is trying to really try to in my experience because I sit in the steering group for the past year is really looking at how do we understand the products how does a manufacturer put together the right data collection study in place to satisfy both the regulators and the payers which might look at different set of indicators for the same product so that's what we are trying to do with this but also trying to simplify the approach to the assessment of the value through a transparent value framework which is a much simpler way to assess medicines and their value in terms of four specific criteria with three different type of degrees of value so that could, if you look at it from the European perspective transparent value framework that is what is we have actually only been filling this one for the first product last year and it actually works well because it gives you an idea at first glance if it is all red particularly if it is curative and has a high response rate you see clearly that this is a product that has value but you can accommodate for different problems or issues that are available and from a European level you can see that this works for everyone and then you can go at a different national or individual or investment level to see this might work in our budget this might not work in our budget the transparent value framework was generated by the process of corporate responsibility in pharmaceuticals one of the subgroup was initiated by the European Commission in 2010 under commissioner for industry and that's one of the subgroup work exactly on this mechanism of co-ordinated access for often medicinal products and developed this transparent value framework in the last three years we have assessed this mocha process have been included in 14 pilot projects on different products and we as your orders provide the patient expert so that there is a conversation with the manufacturer with the patient and the payers but effectively because of different stages of where the products came in we have used it only I think the first time was last year on a very specific product and it worked well and even the manufacturer said this has helped us reflecting on how we structure our value what do we need to do else in terms of research that I think this could be a basis for a much greater coordination and you know we are aware of the different type of co-operation on joint negotiations between countries but also the valeta declaration in terms of negotiation on prices and grouped amongst countries that's it thank you so do you integrate also the people of the EMA in this mocha process for example yes that the first time ever that happened was in September last year so it's coming and in a number of that is the fourth part that you need to integrate so the regulators and this is happening but it's happening at a slow pace because in the end you need to convince them after the mocha sorry we need to convince that group before entering the market the regulators well if the product is not approved then it doesn't go into the market so that is certainly a preliminary condition for it but like in the case of prime we think that having a early dialogue to understand what are the between all of these parties including the patient it's necessary to make sure that the data that are gathered do satisfy their regulators first and then the assessors and then the evaluators and then the assessors so that we don't waste time because if you have to do them in sequence then it takes much longer to have an approval any other question please I saw on the one of the first slides that you mentioned something about patient mobility and I mean the cross border accessibility my question was do are there any databases or some evidences on how to do this for countries who are not yet affording or reimbursing some I know there are some regulations, policies European policies, national policies but just wondering if there are more details I give you an example that might be more practical it's the case of a product called for a rare disease called ADASCID which is an immune deficiency disease which in more figurative terms the patient with this disease are called bubble babies those are the babies that are born with no immune system and they have to stay in hospital forever as long as they live there is one treatment that is perfectly efficacious it's called stream valleys and is given at the hospital Sarrafele in Milan this disease is very small very rare, we're talking about 10-15 live birth a year so many people from the people that have that have been able to access this treatment through the system of recognition of social system between countries not through the cross border healthcare directive as yet what we know is that the cross border healthcare directive because they have some very good points such as the constitution of the European reference networks it doesn't work so well in the prior authorisation of accessing medicine or products ones that are not available in one country so if that is the case you still have another possibility which is a 2004 regulation to access to demand to request for the access and recognise the expense that you have had through the system the hospital Sarrafele has extensive experience in doing this because that is really the core of their work so they can find ways on how the necessary paperwork should be done but when we talk about innovative treatments that is not always the case and this is one of our recommendations particularly on compassionate use making sure that if in a country there is a compassionate use under the cross border healthcare directive rules they should be able to access in this compassionate use but that is not always happening particularly because the most innovative one are rather expensive close thank you it's not easy at the summer school which I encourage you to participate you got a day you got every half day session on each of the specific ones so condensing it in an hour the two areas it's perhaps a lot but hopefully I've done a good job in doing this much appreciated my daughters will love it