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An introduction to european market access

Feb 22, 2022
My background is that I'm actually Professor of General Public Health Practice at the University of Sydney, Australia, and I think I'm their newest visiting professor, having been appointed visiting professor here at Imperial in January working with Majeed for the last six years. I've been working in the UK and varying activities, reinventing myself a bit, but part of that has been working at biomed central as a medical director and continuing a research profile and he can probably tell you about that at another stage today. I want to talk to you about the work that I've been doing for the last two years and this is an area that I think is of increasing concern in primary care now that the consortium will take over some of the commissioning of pharmaceuticals as well I want to talk to you a little bit about how price reimbursement and

market

access

works in the European Union many of you have experience in this area because there is a lot of terminology and I just want to jump on the terminology no so if I catch you or you can raise your hand and I'll stop and do one I have an Australian accent which is difficult but apparently very very interesting but it gives me the opportunity to speak very fast so if I speak too fast please let me know and I'll slow down a bit too So PRM stands for price reimbursement and

market

access

, and these are the three key features for introducing any new technology. a health care market, whether it's a pharmaceutical drug, whether it's a research technique, whatever, price reimbursement and market access the three ways that these products enter the markets so we'll talk a little bit about them ok i guess the first thing to think about is what happens in a pharmaceutical company and how do the products get to market and i guess i'll tell you i've done the american thing i've also been a medical director in the industry Pharmaceutical inside and out. from academia so in my time as chief medical officer I learned a lot about how companies work what happens is you have a pharmaceutical company that has a research arm now sometimes they have the research arm inside the company and sometimes it's outside and At the moment with the banks collapsing, what is the safest industry for all the pension funds to put their money into the pharmaceutical industry?
an introduction to european market access
Consequently, the pharmaceutical industry is in a renaissance in terms of pension funds, where do people invest their money for the future? Tier 1 industries, which is the pharmaceutical industry, how does the pharmaceutical industry maintain its status? Well, you have what's called a pipeline of new drugs, just like new products sell out, you have a pipeline of new drugs coming out, and a company is just as good. like their pipeline so companies build on what they're coming out with and have particular areas of interest now sometimes some companies don't have to buy marijuana. ave pipelines and they buy companies, for example, Roche bought Gentek and that's how herceptin came about land to a receiver and how Gentek's ceptin came about, so Roche went out and bought Halas bolo company and that's how we have the best camp for their drug.
an introduction to european market access

More Interesting Facts About,

an introduction to european market access...

Herceptin so many companies have it within a pipeline or they get it without now this development pipeline from research to sales it can take how many years do you think five ten around 15 to 20 depending on the drug it's an awful long process because you start at end of research with something like each company has about 50,000 molecules and they have to whittle down the 50,000 molecules with very little proof of concept to something they're going to use now. I can tell you about MGM that and this is public knowledge that they bought a melanoma product six years ago that they've been working on at Stanford labs for ten years before it's a bit like knowing how Pasteur developed the urization paste had he had a cold and his nose fell on an agar plate and then he found out that the lysosome was very good for pasteurization well this researcher in a lab at stanford had a research student who had a cold it happened when he looked at his genetic makeup he had an aberration particularly useful genetics that produced a compound that works against melanoma it was cold so Amgen bought the company for three billion dollars based on the results of twenty patients this product is still five years three to five years from the market So, when we look at the investment costs of the pharmaceutical industry, they are huge and one in five products is c ae and we'll talk about why they go down so the industry has this has a long time frame has a high risk activity and has to have a pipeline running so it starts with research and then the medical area helps to setting up clinical trials and clinical trials essentially in the first instance if you have a molecule First you have to see if the molecule works so let's call proof of concept it doesn't do anything that we think it does but we don't know and sometimes that is He does animal models first, and they usually have a full breed. they willingly developed mice that have a particularly good genetic makeup to test these things that they called lysis knockout mice because they knock out parts and so the doctor tested and the first set of tests is, like I said, proof of concept does this do this? drugs do anything and that's called phase one and phase two is safe and if you remember what happened in northwood park with those six men who had major neurological problems that was because they were doing a phase two trial to see if it was safe and guess what you learned it wasn't safe awesome now let's talk about safety safety is a pretty tricky thing because a very unsafe drug that was off the market for many years is one of the best drugs we have right now to treat some hematologic malignancies alignments do you know what falooda is might hairy might cause birth defects the little eye that was used to prevent nausea during pregnancy is actually a very, very good antineoplastic agent so when you're evaluating safety one of the ways to evaluate safety is the balance of what has to be safe for now if everyone is using it as a medication for hypertension, It has to be safe across a broad spectrum, but if it's used for a particular niche of people who have very bad cancer and maybe only have months to live, they can tolerate a different level of safety the newer it is in our general days. , so the security phase then goes to phase three which is called really, this is where the health economics comes in and it's this product really, really we're going to add anything in the world that's worth they're spending money and that's what price reimbursement is all about market access is it worth spending money and how do we determine if it's worth spending m First of all what happens is companies set up and take a look at the economics of the health and outcomes research and that's the area so what happens first is we get the drug then we have to decide if we want to try it and countries decide on that in regulation and the European regulatory agency it's the European Medicines Agency and there's a drug research agency in the UK but the EMA is the agency that says it can test the drug and what the EMA says - we think it's safe enough for you to try it number one and it also tells us who you want to test it with go ahead test it on five foot two people or five foot seven people so what the company has to provide at that point is also what's called a label that has to say that you have to tell us exactly what you want to use this drug for and the dosage so the company will provide what's called a what-is-drug-use-and-dosage label and it goes to regulatory approval once it has regulatory approval in EU countries decide whether they can afford it and how they decide if they can afford it is through a health technology assessment at HTA and the agency that conducts the health technology assessment you within england are nice most US health technology assessments in england the scottish medicines agency SMC does not do it in scotland wales also has its own agency and in europe it is done in many different ways.
an introduction to european market access
We're going to talk about how each country does it a little bit differently, so the HTA does an assessment on getting a refund approved and then what happens in this country. It's going to be quite interesting because now with the startup, the level of decision on whether a product will be incorporated in any region, it will be shared among the commissioners, so the HT could say yes, we approve that drug, but you know , the imperial trust might say we can't afford it so we're not going to get it right so that's the background and then at the other end the company starts trying to ket spoil the drug make it and sell it now if we take a particular drug called Enbrel, which is a drug that rheumatoid arthritis uses and is used quite commonly right now. paracetamol molecule bill's molecule if the paracetamol molecule is the size of a tablet the enderal molecule is of size R from here to San Francisco it crosses the Atlantic four times at -4 degrees in its transportation and manufacturing of products and then there are a and purification requires albumin and we know where albumin comes from unfortunately it comes from cows and cows can have CJD so you can see even the manufacturing process every step of the way can have problems particularly for these molecules uncertain and uncertain so thinking this end of marketing, manufacturing and sales is very we think it's very simple it's also a complex part of the procedure and it's also regulated by agencies like the federation al si gives the agency federal drug that's how that's how the process of drug farm sealant products is made in drug companies okay like I said, paying for these varies from country to country and like I said the first thing that happens is the effect that's evaluated for safety, then the efficacy works, and then the cost effectiveness, so that's the order of how a drug gets to the market. market and in the process in certain countries this implies more doctors importing it more patients importing it but in other countries it really is an economic argument so there is a wide spectrum I used to be clinical myself as a doctor I could say really that drug and then I could convince the hospital to put it on the formulary but it's not that simple these days okay okay as we talk phase one phase two and phase three phase one trials and phase two usually tell you about safety and efficacy and phase three is usually about cost effectiveness and it's the large randomized control trials and what they usually compare it to they used to compare it to a placebo why don't you think that compare it more to a placebo? why shouldn't it? why shouldn't the RCT be involved with a placebo? it will be a placebo, isn't that the highest level of RCT? we say it's the gold standard if the person is going to die you don't want to test against the standard of care because there's something out there so we say test against the standard of care and if there isn't a standard of care that you can try it for example you can have a comparator there called the standard of care is the comparator where in the country you may not have a comparator then you have to once again trust the doctors or the patients to give you some information. a and what you do is you do a practice, a treatment practice survey to find out what the crashes do in terms of your practice and we have to do international surveys right now there are 30 doctors in 12 countries in four different areas looking at what the doctors do it with individual patients in different areas of oncology ok this is a tricky slide but all I wanted to show you was I'm going to go through it quickly to show you how every country is different this is what happens in the UK and particularly through Nice, so you have the license that I said was the regulatory activity, then once you have a label that tells you that this drug can be used for this particular problem, once you go to label, the company determines a price and that's the type of consulting I'm involved in how the company determines what the correct price for this product is and then goes to Ni za, Wales or Scotland to be assessed to see if it is in the redemption recommendation range and then after it comes out in this country it will go to the consortium to see if they want to buy it so the process in the UK starts with a license and a price is set within the and then Nice decides if they want it and then the consortium side if they can afford it so if we take the next one this is what happens in France France just changed their system they have what called a Transparency Commission that analyzes their medicines, which have a type ofsimilar process, they're licensed, they have a healthcare technology assessment, and then they're priced, so they don't set the price, the company doesn't set the price first, they set the price after negotiation through healthcare technology health.
an introduction to european market access
The assessment and why France is kind of interesting no it doesn't look bad in the market and don't worry it's tricky the slide is to the left side of what's really interesting they do two sets of rating . s rate the drug on its innovation and disease severity so they say it is a major disease is a major moderate minor disease what is the level of importance of the disease it is treating and after that they say so we have the disease is the important disease then is the important drug then the SMR rates the disease is a the really important disease and the ASM rates the product how important the product is compared to what is already out there and this is how France decides if the drug will be reimbursed in the country yes exactly exactly and i'll show you let me take the next one and you'll see what's the definition of importance less and less is important right?
If this is a graph showing ASMR ratings over the last three years in France, they don't define it, they just narrow it down, as if I one is of high importance and as in our five, we really don't think you should get it anywhere. premium price in the market and as you can see the number of ones is quite small and the number of fires is increasing and why is that In case most countries will have tight budgets so let's reduce but the level of importance is somehow done by committees, even with a good deal behind closed doors, but the way companies prepare a dossier to introduce the concept of level of importance is by what is called unmet need and burden of disease, so what we would be doing in our company to try to help a pharmaceutical company get reimbursed, we would say what is the unmet need, which is what is the epidemiology of the disease, cancer r of ovary is increasing in the world. it is not, the unmet need in terms of ovarian cancer prevalence is not changing; however, if we look at the unmet need in terms of the value of treatment in ovarian cancer, the treatments do not prolong life, so there is an unmet need because although the volume of disease is not changing and yet it is one of the main cancers of women, so it has an importance, although the volume is not changing, the treatments do not prolong life, so there is a burden of disease. there are people with the disease who are not receiving the treatment that can improve them, so the unmet needs first, what is the epidemiology, second, is there a burden of disease, and third in that area of ​​importance is what is the eligible patient population that should be getting the drug well that's how you determine the importance and we provide help to provide the evidence of that kind of activity on the need for this product so that's disease related so there's a need for this product in relation to other products on the market, for example, does this product provide any general advantages over other products?
I'll get to that in a minute with some of the glitches, but this is interesting because everyone is contracting the economy and France in particular. so more and more drugs are eroding to the level where they're going to be virtually non-reimbursable at a company level once we're prepared to accept and when you're thinking about the huge prices remember I just told you that companies they can pay up to 3 billion i don't know how much rosch claver gentek but it was a lot of money so you are in front of these molecules spending a lot ok so um so that's france it's alright astray alright germany just introduced three and each country does it differently germany just introduced a whole new system called em nog and i won't tell because the german words about this long each one of them but in it but you can look it up yourself but M nog and M nog is their new agency that is evaluating drugs before that it was mostly physician based Collisions thought it was a good idea and refunded, but in Germany M nod appeared and what a nog.
The first thing it does is send and this is a bit like what happens in this country, it sends the file provided by the manufacturer on whether the drug is profitable to an external university agency called Equis and in this country it is done so that there is an EMR there is an evaluation an evaluation of the agency and the universities that do that Southampton Sheffield York and anyone else who wants to go play there all three that they are doing right now for these universities to double check the evaluation that the manufacturer did so that we do Help the manufacturer provide a dossier to the company.
The file, which takes us between eighteen months and two years, and has about three hundred pages. Each particular article that we put up, because we do a systematic review, is reviewed by an independent agency and evaluated. to whether it should be in the dosia in the summary document submission for us to do all the work and then the agencies don't trust the work that was done and they do it again, which is fair enough because we do the work and they get it we deliver to the pharmaceutical industry. company and they can do whatever they want with it they can use the da C or not so there has to be some kind of regulatory test so what happens is we in Germany review the dossier and it provides advice to the regulatory authority GBA pricing in the MS nog and that's this benefit assessment with my mouth this benefit assessment here and then the Essman benefits continue and there is a decision whether the drug will be acceptable to be put on the market in Germany and set prices and then the Germans do something very interesting they say because the price is difficult to determine they say well we are going to let you have the price you want for the first year and after the first year we are going to see what is the effect of your medicine and then we are going to revise your price so you can charge whatever you want for a year but what if you charge we will revise it at the end of a year and the reason why they do it they say until a product is on the market what c ual not a bad idea, how can we evaluate its effectiveness or how it is used?
Because it takes time for a product to be released, used and tested. outside for them to say we'll give you one and hear and then come back and then we'll negotiate after a year on price well this is a new system and it's only been in operation since april of last year so not even the first few medicines under this system have come back to change the price so in Germany it's wait and see how this process works kurz Germany so we have the UK doing well with an independent assessment which is nice again we have France with a Commission of transparency that rates the important relative importance of the disease and the drug that I have Germany that says to provide the dossier we will review it you can do whatever you want for a year if we like it and then we will review your price so everyone is a little different , no, that's Spain Spain went completely bankrupt and in fact some of the poorer regions have not paid for their medicines and hospitals for the last three years, so that Spain went bankrupt, but what you have is once again a central regulatory agency that determines the renegotiations, but the point about Spain is all made at the regional level and I will compare it later, each region makes the profitability for itself and decides if it wants to the drug and as you probably know from the Mediterranean countries, the northern regions have money in the southern regions don It is not so, consequently, drugs can be accepted in the Catalonia region and they are not in the Castilian regions, so you have these situations in countries that will happen here with the regions in charge that will be able to obtain drugs and others will not. that's what's happening in spain now spain does something very interesting he says i'm not sure i really think i know what you're telling me is true so why don't we share the risk or if i spend a lot of money i want you to reimburse me, so there's a lot of deals that regions and governments do with the pharmaceutical industry to share the risk and I'm going to talk about some of them shortly because Italy does it even better so risk sharing is a way of saying if they pretend that this drug works , that's really good but we'll have you risk share if you're telling us a story or it's too expensive so let's take a look at Italy's risk share because they do it very well ok so Italy once again, it's a regional activity and the reimbursement is determined based on the classification and there is a factory price for it so again licensing whats the label second nationally is the drug rentab we'll eventually determine in a region whether we're really going to afford to get it or not so going through that just to get it right in the uk like i said nice like lead agency scottish drug agencies that it's the other agency one of the reasons people look at the scotch medicines agency internationally getting it right is because scott smc published his results very quickly he can give you a result in three to four months some from these other agencies it can take up to a year to evaluate the drug, so you're sitting for a year. without the drug being tested let alone going into production after all the regulatory activities have been done, so SMC is pretty fast, it's moderately rigorous, it gives you a clue, it takes a little bit longer, and of course the gold standard is one reason. why and of course people like an australian accent is the granddaddy of them all is pom skittle benefits advisory committee in australia driving profitability programs they are still leading the way in this type of work starting in australia to ppac so you have good SMC and wales business agency now what they do is assess how much a life is worth how much do you think a life is worth per year ok that would be nice thats true and that extends to the other thats quality of life is tight but on average how much do you think you're worth to this government to have in this world what's up here that's worth thirty thousand pounds a year the government assesses you're worth thirty thousand pounds a year so to keep you in march they're going to spend thirty thousand pounds a year on a product to keep you alive and that's the cost, that's the level, okay, for every quality of life you adjust they get for you is has to be thirty thousand pounds if you keep you got your dope under thirty thousand pounds well he says it's worth it to my people if it's over thirty thousand you're in trouble and if it's over fifty thousand you can forget it no one is worth more than fifty thousand countries looking at profitability of course I'm not talking about the US here I come back and do it another time that's a minefield but here in the EU and most other countries that have some sort of national healthcare the scheme working is worth around thirty thousand so that's the profitability in the UK as I said France has the Transparency Commission the Transparency Commission has the components that the query says so we said if there is an unmet need a disease is there is a benefit therapeutic interpenal that sets, determines and then houses the final agency that says what the price is Germany we talk about free prices for the first year GB a fast free price o Italy and Spain in a similar way is in the regional activity and this is what it will be in your network so that I don't waste my time doing it because you can read that everything is very complicated, but I just want you to understand the concept so that we can talk a little to the So if we're looking across countries in the EU at what is the level of influence in terms of determining whether pharmaceuticals get to market nationally is there a national agency through this is the top five of the EU now if we are thinking about which market in terms of markets sorry in terms of markets what is the largest branded farmers market in the world where do you want to sell your medicines tell us why you brand in the world what is what is the size of the australian market just throw it in 1% now i did because i want you to tell me what you think the size of the uk market is the trick question it's only 3% because they are very checks stringent and what's coming here so if we're thinking EU top five you need to think top five if you're thinking of going into the European market not just the UK although populations here on the life side standard here are not high in the market so when you think in terms of bringing products here you think top five so you know UK Germany France Spain in Italy and quite often they are they include a couple of other markets because they have activities ofgood profitability and they're recognized by that guy from Sweden and the Netherlands because they really have a good regulatory system, so they're often thrown into the mix as well.
Canada has a very good testing system, but they don't buy any drugs, so no one can try to find more. You can completely ruin your market. for example Canada and for example New Zealand have blown up their market for new drugs because they couldn't afford them so there's no market there's not even a price for drugs in these countries this particular technology assessment process of health can cost a company between 50 and 60 million. per country is an expensive activity this assessment activity so you have to decide what is the risk benefit remember smell of fortune ya buying the drug yes they bought it trying the drug and here we are at 10 years since i first got the product, there are five years left for the final evaluation, so we have a regional evaluation in all of them, the regional evaluation in France has very little interest and one of the reasons is that they are still quite unified to determine their activity for example, in the area of ​​things like Herceptin which is called a companion diagnostic well you have to test to see if you have the genetic marker so you can have the drug Frances nominated 20 centers will be the only testing centers for acceptance so they can regulate the market very strictly at the federal level so there is not much but it happens in France at the local regional level whereas in Germany there is something that happens in the local form. but quite strongly at the national level and as you can see initially the regional levels are very important and the region that people pass through and I show the last ones, it has a region of Veneto, the richest region in Italy, so any decisions that are made in Italy are actually made in the Veneto region and are made regionally not locally and in Spain a similar regional region as I said Catalonia around Barcelona the richest region so the primary decisions on drugs and Spain are innate in that region and in the UK as you can see there is no region I've got very good regional activities your trust you know each revision has removed a regional level they say chaise have gone now the PCTs are going to be a very local consortium accessed n ice or determinant and then the local authority will say if they pay for it, so remember how they make decisions.
I have told you what they do and why they do it. importance, how do we give it importance? Do you have a test that compares apples to apples? It's the right comparator and one of the problems with comparators is that if you set up a test four years ago, you don't know what your competitors might be because a new product may enter the market all the time, so if you're a competitor against an old drug for example in the melanoma area there is a big Renaissance now there are a number of completely new drugs coming out for melanoma and in the old world the drugs that were tried with drugs that killed DNA drugs poisons that killed DNA which is the old treatment for oncology the newer drugs have much more to do with immunology and changing protein expression within cells if you care compared yourself to a killer dacarbazine of DNA that is not the appropriate comparator now and it would be said that you have not done the correct test to verify reimbursement because there are newer medicines It's in the market that you have to keep here so it's very important for pharmaceutical companies to think about what is the active comparator and if they don't have an active comparator they have to do a lot of economic analysis which is called indirect comparisons of treatments, going through research studies through systematic reviews to see if you can see that if A was compared to B and B was compared to C, then I can compare A to C and those of you who know the logic of data, that's a real mismatch in terms of logical epidemiological data, but acceptable in economic data, so your comparator is fine. the second thing is that he wants this to work on everyone and we said earlier about how important the age of 6 is ok maybe that's not good maybe his medication is really toxic to the elderly and d maybe he shouldn't be allow prescribing it to those over 70 because they all died from lack of white blood cells so I'm not good with you prescribing it to them I'm going to limit it or maybe the simplest thing is it hasn't been tested in children.
I'm not going to let you prescribe it in children with leukemia because we know it's different, so tell us about your subpopulation biomarkers otherwise, if yours is positive then you should be able to get something. melanoma is BRAF wild type so there are subpopulations you have the right population and you can see why countries want to get to a subpopulation because they have to pay for less people the smaller the subpopulation the less people have to pay the corollary it's also true: if a pharmaceutical company manages to get you accepted in a subpopulation, they can add rackets to an X of the population X subpopulation and create a larger population, so it works both ways, what is the subpopulation? as we have talked about you you know how much this drug is worth in terms of the importance of the drug and the profitability in terms of what life is what life is worth now remember how you said safety and then we said efficacy well safety is pretty important so quality of life becomes important here although it really only helps in the UK and a little bit in Australia quality of life is important because if you're not improving the person's quality of life then what is what the drug does?
Extends life or improves quality of life now where it is important to demonstrate quality of life is it important to demonstrate quality of life for older people or younger people? later on, I know David Cameron, old people, young people, yes, but if you're thinking economically, what do you want to keep part of the workforce, so the argument often is what's the benefit if we can keep people in the workforce, so we're going to look at health-reported outcomes and patient-reported outcomes. or look at how it keeps younger people in the workforce, that's a driver for quality-adjusted life years, that's an extension of overall survival, but the idea in the younger population is do we really have a population that we're really going to keep in the workforce and where this becomes important is in diseases like multiple sclerosis, it's a younger population that wants to make sure that they can continue to work through their emissions and exacerbations, okay, the Next things we talked about a little bit like I said risk sharing and I will talk about that a little bit in a moment and the importance of regional stakeholders in some of these countries now these drugs only have a certain life cycle and a certain patent durability which is larger in the US than other countries so there is regular review of this and there is post-market surveillance in a Some countries to see what is the projection on what are the projections that were determined in the first place t a correct product, are you really selling more or less medicine than you said you were going to sell because if you are selling more, you promised us not to I would because we base our budget impact process on you telling us the right number ok so that happens pretty well but mostly on some quality UK and Australian bit so these are the types of sets of data that can help you make the decision therapeutic benefit we have talked about the profitability model that we are talking about really only for the time set right now in the UK very strongly in Spain and regions budgetary impact meddling each country wants to know what the impact of this on the country's budget quality of life as we said mix things qualities they have I was around, but actually I said what I do e in terms of performance status in terms of patient reported outcomes eq-5d and LRT i see that is starting to become important and as i said direct trials aga Install the correct comparator and if you don't have it go out and see what's going on in the real world and take a survey of treatment patents or something.
There is some interest emerging in innovation and value-based pricing. in this country there is a fraction that is going to be included to talk about innovation, but the innovation that they are talking about is not innovation and a new smart drug, the innovation that they are talking about is innovation in terms of price and cost-effectiveness , it can make the product in the right price range for us, so let's take a look at what's going on in the EU, see what's going on with some of these newer drugs and how they've been tested and how different sets can be can be used for different different determinants can be used in different situations Avastin or bev isuzu map can never be pronounced half of them is a drug now used for many areas its moments are being tested in ovarian cancer but d was used in the metastatic colorectal cancer that was the first presentation, so M CRC is metastatic colorectal cancer and provided a median benefit improvement of 4.7 months in survival.
Overall about your comparator, so people who had metastatic colorectal cancer are at a median of median length of life and it was 28 out of six from 15 months to 20 months not recommended by NASA MSMC got a refund very high remember we said that with an SMI it was but as it was good it was the best French I really liked it so there you already got a different same drug same indication Scotland and England say no France is quite nice thank you very much lo we'll have good so we're going neck for renal RCC renal cell carcinoma so remember you offered a three now that's also used in hepatocellular carcinoma so you can see that's next we're going to do renal and then we were doing hepatocellular same drug different indication again three months acceptable median improvement over placebo PF S is and yet is what PSS stands for progression free survival and some d In these cancer areas where you can't see overall survival, what you're looking at is the time between treatment and progression because the survival history is too long to see in the analysis that progression-free and anti-progression survival placebo they got to 24 weeks 24 weeks versus 12 I mean if you talk to outsiders that you're just extending someone's life by three months or four months and it's going to cost you I know £40,000 a year this is the area where the one we are working on ok once again SMC said no and France said again we like this one too it is enough for us and also in Italy it was refunded but look what the Italian said we have to give ourselves a 50% discount on the first two cycles, so cancer drugs are given in cycles and some of these areas have up to six cycles.
The cycle usually depends on the drug in treatment, but the cycle can run somewhere. like three weeks with a break and then run again so what is happening in Italy they said you can have the first two cycles you would have it but you are going to pay half for the first two cycles the company in those cuts in these countries not much if i come back you are absolutely right and that is oh sorry just backwards. If I go back let's take a look as you can see there is nothing to be expected in quality of life except in the UK.
It's only expected anywhere in the UK, the other agencies will see it as not having a significant impact on decision making and some of the reasons are because some of the indicators are misleading and difficult to map to others, e.g. what has advice and takes into account the quality of the license the indicators takes into account an individual called eq-5d and the EO RTC 30 are the two indicators they use as PR OS the problem with those is they are very generic instruments and there is no a lot of mapping for example they could map the quality of life of someone with melanoma either stigma skin or someone would say posey sarcoma and hiv so one of the problems with some of these PR instruments or is their The accepted mapping instrument is quite complicated and not always accurate.
Am I getting to where you want me to go by answering the question? Yeah, so for example, if I'm this for melanoma, there's a new instrument called, actually, melanoma that looks at skin disfigurement from ovarian cancer, there's one. for ovary, but the mapping is absolutely rudimentary and what happens is that each company is trying to validate their own PR instrument. Oh. I mean, I'd be surprised if some company at work asked you to start validating a PR instrument Oh every company and The classic example, the one that really worked in the first place, was when SSRIs came along and Pfizer did Prime MD. depression scalewell, then you know that Pfizer decided that it could be set up very well.
I think it's Pfizer, one of them, forgive me, fires. They're going to sue me on YouTube. weirder than the primary care instrument that differentiated between drug use and CBT so they developed the variant of the instrument called primary and that started it and you can see each market now trying to develop their own pierrot instruments but like I said well it's going to say map for me because I have to compare a drug for oncology for renal cell carcinoma with a açelya fat carcinoma and I need some kind of mapping activity more and more is happening and then the other way that what can happen is that different companies put different presentations some companies are better to get a presentation and mapping of a couple or set them up eg Herceptin established some PR ORs in the area of ​​breast cancer which are now accepted as a fact breast by what these different indicators are accepted the real problem George good most of paris the real problem with PR o--'s in fas trials e three is that patients usually do not complete them, so the data is always not very clean, you know that when you test on hospital patients, you must complete the patient-reported result, and clinical departments do not follow up very strict because it's run by medical departments who are really just looking at safety and efficacy so their data is often not very good in that area either i shouldn't go on i mean i could go on i stick together ok so let's talk i remember i said a little bit about risk sharing there are three different types of risk sharing that can go you know we said the last if I take you back to where we were the last remember we said that in the bottlenecks of our around me in Italy there was a joint venture agreement that the company had to assume 50% of the cost of the first two cycles is, so that is what we are going to risk share now ok so the first one is we don't want to pay for those people who you shouldn't be putting the drug in the first place we're not paying for the non-responders so if you use avastin or but bev the soup Suzy map for three cycles and they don't respond we want our money back because why should we treat people who don't respond?
So that's the very difficult first tier of risk sharing, the second is when we saw that this is a risky activity that we want you to share risk in real world data for this drug, you pay 50% for the first two cycles and the third is the foot for the first cycle of the non-responder, not just for everyone, but just for the first cycle and there are three examples of where that happened the joint ventures you know, Avastin like I said where the service loved three cycles and that was as we said before that it can be in three different areas Bevis susan has a very interesting new drug it is a drug that does what is called angiogenesis it is a belief now that the VAT, there is a debate, but there is the belief that that the vasculature going to the tumors is inadequate and so some of the new drugs actually create a good vasculature for the tumors so other drugs can get in there and kill them because the vasculature it's erratic so the tumor grows which causes the bad vessels to speed up so you want the railway to be good so the poison can get in so Bev assumes F is one of those drugs and so So Weston angiogenesis agent is fine take a look remember how we said and this is back. to the point of utility data, the areas that look at, certainly SMC and well, we'll look at the pyrotechnic utility data. how this drug really improves your life and if you want to try and quite often it is done with compensating activity would you trade this for that?
Would I trade a scar for being able to walk two feet each? headache in the morning from being able to go to bed is a fairly frequent trade-off situation and they are kind of vignettes that are made for them and we talked about the population of eligible patients who should be given the survival data that we talked about as i showed you in oncology the survival data is pretty tricky because everyone dies and you really only extend life for a short period so what you really want to do is really give them you know progression free survival is what you're looking for how long. until their next episode where they are going to need some treatment or something and if we say what is the population that is the end of the formal bed I can go I can expand on any of the parts that people might be interested in are focused on ecology because that is one of the main areas in which we work.
Rheumatology is quite similar and any knowledge is quite similar. The area in terms of pricing, what we call small molecules, which are the cheapest drugs, is really like a pharmacy because there's not a lot of innovation there, I usually tend to be priced like what is generic paracetamol versus panadol, that's why I haven't focused on that area because that's not the high-cost end of the market, the other thing is Aldo. I was aware of the two new things that are probably interesting, what's known as orphan drugs in orphan conditions because the FDA decided in small areas and in this country as well that if there were too few people you could risk a very expensive one. drug, so if you have less than a certain number of people in the country with the disease, the thresholds go up, for example, acute lymphoblastic B-cell lymphoma, and drugs relative to the new system coming up, which is Called value-based pricing, the problem in terms of value-based pricing is a bit more complex, but that will mean that they're going to set price weights for different diseases. you have a particular weight and nice will set them up and you're negotiating to set them up your drug has to fit within the weight of the price for this particular disease and that's the basis of the new value based pricing that's coming in so I'm NOT happy For stopping there as you can see I could probably go on for quite some time but I'll stop there if there are any particular questions or anything that isn't clear or I'll clap my hands thank you.

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