Welcome to Free Thoughts, a podcast project of the Cato Institute's libertarianism.org. Free Thoughts is a show about libertarianism and the ideas that influence it. I'm Aaron Powell, a research fellow here at Cato, an editor of libertarianism.org. And I'm Trevor Burrus, a research fellow at the Cato Institute's Center for Constitutional Studies. Recording today's episode live from the 2014 International Students for Liberty Conference in Washington, D.C., our guest today is Alex Narasta, the immigration policy analyst at the Cato Institute's Center for Global Liberty and Prosperity. The format for today's episode is a little different from usual, because instead of Trevor and me asking most of the questions, it's going to be you, the audience. But that said, I'll start with the first question for Alex, which is a rather broad one and probably the most important one for a room full of people who have come to listen to this talk, which is, why should libertarians care about immigration? Thank you. I think it's good to begin with the most important question. The freedom to move and the freedom to move without government restriction is one of the most important ones in existence. When the French liberals were arguing in the 17th century, 18th century about capitalism and free markets and how to reform the system, they came up with the phrase, laissez-faire to describe that. Now you've all probably heard laissez-faire. The second part of that phrase that's not repeated often is laissez-passeur, which means basically a freedom to move as well, because part of the pre-capitalist restrictions at the time were that they restricted the trade in goods and services across borders, restricted the flow of capital, but also restricted the flow of people. And back then they understood how an important part that is for individual liberty as well as free markets. Since the end of World War II, we've seen a liberalization of a lot of things in the international economy. It's easier to trade across borders than it was 70 years ago. It's easier to invest in other countries than it used to be. It's easier to move your patents and intellectual property across borders. But something that's still very restricted in very much an early 20th century way is the freedom to move across borders, to work in other countries for employers voluntarily, to sell your product, to sell your labor, which is for most people in the world throughout history the most valuable thing that they have, to try to find somebody in another country who will buy that, still heavily restricted, vastly restricted by the government and a huge impediment to human freedom. Now I talk about this in the American context mainly, but these problems are sometimes mainly worse in other countries. But it's important, I think, to get a notion of just how restricted this is. As most of us in here are Americans, we understand, you know, we have this proud tradition of like Ellis Island, of, you know, open borders that many of our ancestors came in on.  But now that system has been replaced by something that looks like this. This is put together by a bunch of immigration attorneys at a law firm I believe in California. This is the 30,000 foot view of it. If you are not a highly skilled, foreign educated person who doesn't immediately have a job offer in the United States, and there are only 140,000 of you a year, then you can probably get a green card. If you're directly and immediately related to an American citizen or sometimes a green card holder, you can get a green card. If you are a refugee, some of you are allowed to get a green card and there's 50,000 green cards set aside a year for a diversity visa for a lottery.  There is no category for a low skilled immigrant, which is how almost all of our ancestors came to this country with less than a high school degree or even while being illiterate. So the notion that people can come here lawfully is just wrong. Now if nobody wanted to come here, this wouldn't matter. This would just be something that exists on paper. But because the wages across countries differ so vastly for the same work, it matters a lot. We have this concept called a place premium. It's how much more you would earn in the United States compared to what you would earn in your home country for the identical work. So it's identical amount of years of experience, identical types of education. So a Mexican who moves the United States with a high school degree can expect to earn four times more than he does in Mexico. Guatemala and four times more Indian seven Vietnamese nine Haitian 16 fold. The average is seven times increase from developed countries to the United States. So this enormous pressure, this enormous economic pressure to come here lawfully is constrained by a legal system that looks like that. There is no way for most of these people who want to be able to come here to fit through that legal system to come here right now. Now most of you are young. You haven't been competing yet in the national labor market for jobs. I would bet that almost all of you would be willing to move across the United States for a 30% higher increase in your pay. Maybe definitely for a 50% increase. Are there other good restaurants there though? Yeah, are there good restaurants, that's a good question. Concerts. But these people are facing an amount of wage pressure far more than any of us will ever face in our lifetime probably. But there is no lawful way for them to move. So that's the basic. But this also would help us out too, right? I mean, generally having more people makes more prosperity. If not, then you could make the exact same arguments against immigration that you would make against newborn children, right? Yeah, so one of the problems I think with the immigration debate from the pro-immigration side is we talk about it in terms of what's good for the immigrants. Now everybody knows that immigration, almost everybody knows that immigration is good for the immigrants. You talked to Tom Tancredo, a Republican in Colorado who despises immigration. And he will admit, yeah, immigration is good for the immigrants. The problem is, is it bad for us? Is it bad for the Americans, for the natives who are here right now? And what we find generally is the same thing that Julie and Simon found back in the day, which is more people, people are the ultimate resource. You know, people create jobs that they then occupy. They're entrepreneurs. They're consumers. They're inventors. They create a lot of the wealth and circumstances that improve themselves. Having more people here means you can have a greater division of labor. It means that we can have people who are more specialized. And what's more interesting is immigrants come here because there are jobs that are offered to them. We saw after the wake of the Great Recession when the housing market crashed recently, we saw immigration from Mexico drop off to a net zero. Mexicans primarily worked in, not primarily, but a large number of them worked in the housing sector. They worked in housing construction or in supporting that. When those jobs evaporated in the wake of the housing collapse, we saw immigration from Mexico drop off because there was no opportunity for them to come here. And that's the same pattern we see throughout American history. When immigrants come here, they're attracted to jobs and opportunity. When they come here, they make us more prosperous by adding their money to our economy, by buying the goods and services, by starting new firms, and by adding to the specialization of the U.S. economy. So, first of all, if anyone has a question, you can start lining up and we'll just call on you. The mic right here, you see. Sure. The incentive for a worker to immigrate depends on the price, the place premium, and also depends on what type of labor they are. I'm wondering what the place premium is for low-skilled labor in particular. So, this place premium right here is for people with a high school degree. So, it's not the most skilled labor, it's also not the most unskilled labor. I can't tell you off the top of my head what those numbers are, but most of the workers in these countries who would come over would be very low-skilled compared to most Americans, and it's somewhere in the order of similar to this. Do they stay low-skilled once they come over, or do their skill levels go up, or either within their own lifetime or intergenerationally? So, it depends quite a bit on the immigrants themselves and how long they want to stay in the United States. A lot of immigrants are what are called sojourners, which are temporary. They come here for, you know, five or ten years or they have a goal of money they want to save up and then they want to go back home to their home country. They don't usually invest very much in their own education. They're here to work, they work very hard, they save their money and they go back home at the end of it. For immigrants who are more longer term, we see about half of them in the course of their lifetime become fluent in English, fully fluent, conversationally fluent in English. Most of them come here without English fluency, so that's a big improvement. We also see sort of a general increase in their education. A lot of them earn their GEDs while they're here, as well as go to community college and take advantage of that, but you don't see a huge increase. You don't see a whole lot of people who come here with less than a high school degree and end up being PhDs. So, you see a relative increase, but that's only for legal immigrants in the United States. You don't see much of an increase for illegal immigrants or unlawful immigrants, and the reason why that is is if you're unauthorized and the government could arrest you at, you know, any time and deport you, so it's irrational for you to invest in country-specific skills like learning English if you could be shipped away at any time and lose that entire investment. So, what we see is after the last amnesty, the Reagan amnesty in 1986, we saw an increase in education by those legalized illegal immigrants who try to increase their wages over time. So, one of the more interesting things is if you want to increase the rate of education, sort of assimilation in the United States, increase the rate of education amongst illegal immigrants who are here, one of the best things you can do is to legalize them and remove the fear of having them arrested. Now, how does the retention rate, the language acculturation rate compared to past, there's a lot of people here who say, oh, they're not speaking English. No one's learning English anymore. How does it compare to everyone who came here before? So, according to the best data we have compared to previous immigrant waves, this immigrant wave is learning English faster than almost any group in American history, with the exception, of course, of people who came here learning English. So, what we see is with current immigrants about half become fluent in their lifetimes while here. With their children, you have somewhere between a 97% and 100% English fluency rate. And that's the second generation, the children of immigrants born here are second generation. Third generation, it's 100% English fluency. You basically have another third generation of Hispanics who are here in the United States. 77% of them are English only and 23% claim to be bilingual. Now, if you mean bilingual, my father claims to be bilingual and he speaks Farsi as if he was four years old. So, like almost all Americans, we don't speak other languages and that seems to be reflected in immigrant assimilation over the long term. Next question. How did these restrictions on immigration came up and what are the 21st century paths to deregulate it and are there concrete measures that have been taken in the past few years? Great question. So, I'll talk about in the American context. The first immigration law passed in the United States was in 1790, it was called the Naturalization Act of 1790, it was an open borders law. There were no restrictions on anybody who could come here. It was a restriction, it said that you had to live here for two years, be of good moral character. Unfortunately, you had to be white too, but in order to do that, then you could become a citizen after living here for two years.  But compared to the time, there was no gender restriction on becoming a citizen, there was no wealth restriction, there was no skill restriction, there was no religious test. That's different from every other country in the world at that time. So it was a pretty open law, and it was a law that basically restricted who could be part of the political system, not who could come here. The first immigration restrictions in terms of restricting who could come here were passed in 1875. They were restricting people who could come here as indentured servants who were basically hired to come here for a temporary period of time. It was targeted against Chinese immigrants who were overwhelmingly thought to be prostitutes who were coming over here. After that, you had the Chinese Exclusion Act in 1882, which restricted immigration from China entirely. That was the first sort of nationwide ban. After that, in 1907, you had a gentleman's agreement between Japan and the United States where the Japanese said, we will not create any exit visas for Japanese citizens. And the Americans said, well, if none of them have an exit visa, then we're not gonna let them in. So it was sort of an agreement not to let any more Japanese immigrants in. 1917, you had the Literacy Act, which restricted immigration to only people who were literate. They could be literate in any language. It had to read a few sentences from the Constitution, but in any language from wherever they came from. And then the first national origin quote as a 1921 were put in place, which restricted European immigration. From that point onward, we've dealt with a very restricted immigration system or very few people who are able to come here who want to actually come here. We reformed it and opened it slightly since the 1920s. We allow more people in from East Asia, for instance, it's now possible to immigrate as an East Asian and a South Asian lawfully and to become a citizen. Thank goodness. You're able to immigrate lawfully from Central and South America. But in terms of the reforms that could be done going forward that are being at least contemplated, one idea is a large scale guest worker visa program, which would allow people to work temporarily in the United States and then go back home. That's something that's been adopted here in the past with good results and another places. Another idea would be an auction system, which would be to issue a certain number of green cards and auction them off to the highest bidder. Another system, which would be a point system, which would be, you get a certain number of points if you're this educated, certain number of points if you speak English, certain number of points if you have an employer who really wants you, a certain number of points for all these other different classifications. If you get X number of points, then you get to come here and live here. That's something that Canada and Australia has as a system. It favors high skilled immigrants. Another system could be a tariff. So you basically say we're gonna charge $25,000 or some amount for a green card. You pay that, you get a green card. So these are all different ways that are being at least talked about or contemplated to open up immigration. Next question. Is there data on how much money is being sent home from immigrants? And if so, how much and where does that money go? Excellent question, I think it's a lot. Yes, it is quite a bit. The World Bank came out with a study about a year and a half ago. It measures about $600 billion globally in remittances across the world. They primarily go to countries like Mexico and Central America, as well as a lot of Central Asian countries where there are immigrants working in Asia and other places around the world. What we see is that money is primarily used for day-to-day expenses in these home countries when they're sent back. So a lot of food, soap, things like that. But after that, the second most common thing they spend it on is investments in businesses and education for their children. So what you see is a lot of places like certain states in Mexico like Michoacan and Zacatecas, which have sent a lot of immigrants, is you see a huge thriving small business sector in these states sort of grow up, funded by the capital that's sent away by Americans and other immigrants. And this is something that we've seen historically in places like Italy when Italy was a poor country. So it's quite a lot of money and it's a lot more than foreign aid that's sent across the world. And it's a lot more effective because it's actually put in the hands of the people who know what they're doing rather than managed by international aid bureaucracies that pretend to know what poor people want. Yeah, good point. Next question. How do U.S. immigration restrictions compare to other OECD countries and their immigration restrictions? And as a corollary to that, what sort of opportunity costs does the U.S. face by restricting immigration relative to other countries? Wow, those are two fantastic questions. If you compare the United States to other OECD countries, we're one of the more restrictive countries. We're, depends how you measure it of course, but in terms of the annual inflow of immigrants relative to American population, we let in about a million people a year lawfully on green cards compared to our population of about 310 million people. So it's about three-tenths of 1% inflow per year that were added by immigration. By comparison, a country like Switzerland has about 1.5%. So they have enough immigrants that adds to their population of about 1.5% per year just from immigration. So they have a flow that's about five times bigger as a proportion to their population. The percentage of Americans today who are foreign born is about 13%, which is still below the high that it was in the late 19th and early 20th century. It peaked at about 15% as people who were foreign born. So we're actually below that high. But a country like Switzerland has 27% foreign born living within its borders. Canada has about 20%, Australia has about 21%. So these are all countries that have more immigrants as a percentage of their population. These other countries also let in more workers as a percentage of their populations, mostly high-skilled workers. Only about 20% of Americans of immigrants to the US are workers. In terms of they're hired by American firms. The rest are mostly family reunification. So other countries it's reversed. Usually about 20% of other countries they have a family reunification. The rest are workers. So compared to others, we're pretty restrictive nowadays. Where we're very, what we're very good at is sort of the cultural and economic and civic assimilation. So we have birthright citizenship in this country. People who are born here, even if their parents are unlawful immigrants or illegal immigrants, get automatic birthright citizenship. They're not living in a legal black market if you're born in this country. That compares to places like in Germany or in South Korea or in Japan where you have generations of people born there who are not citizens. You see a lot of problems with that. But here we very quickly and very rapidly assimilate people. So that's sort of one of the big differences. Next question. Yes, obviously due to government interference there's a problem for low-skilled workers already in the United States to get jobs. And I was wondering if increasing immigration, allowing immigration to increase would mean that those low-skilled workers that already exist in the U.S. would have to compete more with immigrants. And if increasing immigration should wait until after some of the other problems with overpricing labor and so on and so forth is taken care of. Great question. Thank you very much. What we've seen is from 1990 to 2006 there were about 30 million immigrants who came to the United States. And the most negative study you can find in the peer-reviewed economic literature finds that that decreased the wages of Americans with less than a high school degree by about 4.5% over that time period. So you saw immigration that was equal to about 10% of the U.S. population lower the wages for low-skilled Americans by about 4.5%. Now the reason why that is is because most immigrants are either lower skilled than the average American or higher skilled than average American. Most Americans are in the middle. We have some college or a college education. So most of us are just not competing with most immigrants who come in who are much more likely about third of immigrants have less than a high school degree, about 20% have a college degree or more. So there's not much competition with directly with Americans. But what you see is when you dig into the data you actually see, and that's the most negative study that I mentioned, you dig into the data, you look at other studies, what you see is because immigrants are still different from other Americans and the number one most, the biggest difference between immigrants and Americans is anybody, anybody? Language, language. So we all know we're all Americans. I bet very few of us are bilingual. In order to do well economically in the United States you need to be able to speak English. If you're a low-skilled immigrant and you come and you don't speak English you are relegated to different sectors of the labor market that other poor Americans are not working in because they have a skill that's very valuable. So to give you an example they form parallel labor markets in different sectors of the economy so they're not competing directly. So to give you an example about a restaurant low-skilled immigrants who work in restaurants don't work as waiters or waitresses or hostesses or managers. They work as bus boys or janitors or line cooks so that they work in those areas. What that does is it allows restaurants, owners to open up more restaurants as a result of having more low-skilled labor. It also pushes up low-skilled Americans who have the ability to speak English into higher-skilled professions like waiter, waitress, hostess, manager, et cetera. And that's what we've seen across the labor markets in the United States. So most studies like the ones by Giovanni and Perry find that because immigrants are still different from Americans what economists call compliments to them and not substitutes you see a general rise in wages in every urban area where immigrants go as a result of more immigration. So they compliment rather than substitute with Americans and that's what we see pretty much across time with this. Next question. Are there any restrictions or barriers for immigrants trying to open businesses or get licenses to work in the United States? A lot of that stuff is local. So in a place like in Georgia, for instance, they passed immigration enforcement law in 2011 and in order to get any kind of license in the state like a registered nurse, you had to prove that you're an American citizen or lawfully in the United States. Of course this caused so many problems because so many Americans can't prove that. About 25 million Americans actually don't have the paperwork to prove that they're American citizens. They had to delay that because otherwise they were gonna like kick out about a third of nurses in Georgia and get rid of their licenses. So they delayed that pretty much indefinitely. There is a law in Arizona right now called the Legal Arizona Workers Act which became law on January 1st, 2008.  It's called the business debt penalty and it's called that by its supporters who think that they're getting tough on business for hiring people. But in terms of like business licenses, it's very much state by state but most states do not restrict that. What it does do however is it's difficult to get a loan if you don't have a social security number. It's difficult to get a loan if you don't have evidence that you're here lawfully. So you do see restrictions in that but there are a lot of businesses owned by unlawful immigrants. Most of them in service sectors or they're contractors of different types. It seems like just being unlawful too in terms of being averse to banking and being averse to anything that would get you involved with the government which would be running a business one way or another. Yes and it also restricts you geographically. So there are some states that are very strict on immigration enforcement like Arizona and some states that aren't like California which passed a trust act recently to restrict their state level of enforcement and cooperation with enforcing immigration laws. So it really sort of pushes you in the areas that you might otherwise not want to be or start a business. Next question. I'm curious what you make of the sort of special ire you've inspired in the American populist right like famously with your Twitter argument with Mickey Kaus at the Daily Caller but also David Fromm or even like Peter Brimelowsvdare.com and what you think your sort of prospects are of convincing them. This is a great question. This is an interesting question. I think my prospects of convincing them is near zero. I argue with them to try to convince people who are watching the arguments. So it's sort of like the difference between asymmetric warfare and symmetric warfare. So it's like fighting a guerrilla war. Like I don't, when you fight a guerrilla war you don't intend to go after and kill all the guerrillas. What you intend to do is convince the population that you're there to protect them and to convince them to be on your side. So that's the way that I view media relations is to try to convince you all and other people who are sort of in the middle or mildly opposed to see it from my point of view and to see it more reasonably. So I don't think I'm ever gonna convince David Fromm that he should like immigrants even though he's an immigrant himself from Canada and he made it in easily enough to the United States. But what I can do is push back against their arguments because a lot of their arguments, although they're made sort of in a nasty way are things that common people think about. They think about, well, are these immigrants different from previous waves? Are they not gonna culturally assimilate? Are they gonna take our jobs? Are they gonna make us poorer? So if I address those arguments head-on when they're made in sort of the most brutal way and nasty way and I can do it in a way that's somewhat convincing the people in the middle, I think I've done my job as well as I can. Next question. Okay, so I know one of the objections to opening borders or removing restrictions on immigration is the access that legal and illegal immigrants have to benefits that are essentially, some people believe should be reserved for only tax-paying citizens or, I mean, some people object to them entirely, like welfare and all those kinds of things coming from California. Well, yeah, coming from California, I know you can get Medi-Cal, you know. So that's a major objection that a lot of people have. I was wondering if you had kind of like a rebuttal to that or your thoughts on it. Thank you. And it's nice to meet a fellow Californian. I grew up in Burbank in Camarillo in Southern California too. And I remember being a kid and watching the California Republican Party commit suicide by blaming immigrants for every problem in the state. And they haven't recovered from it yet. And they haven't recovered from it yet.  Yeah, it's an interesting question. So I'm one of those libertarians who opposes the welfare state and for everybody all the time. But I think it's important to put it in perspective, like how much welfare do immigrants use in the United States? Unauthorized immigrants right now are ineligible for virtually every single welfare program in virtually every single state. The main exception everywhere is emergency medical care and emergency Medicaid. So if you show up at a hospital room and you're injured, you can get on the spot medical services according to the Imtala Act. Everybody can, though including, and you don't have to show any ID or anything like that. So including unlawful immigrants can do that. And that's one of the main sort of costs. If you're a lawful immigrant to the US on a green card, you don't have recourse to public benefits for the first five years that you're here lawfully. There are some small exceptions to that, but that generally holds for Medicaid and other benefits like that. But even when immigrants have access to these welfare benefits, especially poor immigrants, you see that they use them at a lower rate and when they do have access and use them, the dollar value of their benefits is lower than what poor Americans get. So if you compare apples to apples. In fact, it's so much lower that if poor Americans used Medicaid at the rate that poor immigrants do and their benefits were as small as legal immigrants do, poor immigrants do, Medicaid would be 42% smaller in terms of its benefits. So we're talking about a population that doesn't really use much. In terms of the entitlement programs like Medicare, I hate to, you guys probably all know this because you're smart and well-informed, but Medicare Part A is going to go bankrupt. It's on its way. It's supposed to go bankrupt in 2024 if everything goes well. So probably like in 2021 or 22. Right now, native-born Americans take out $31 billion a year more from that system, Medicare Part A, than they put into it through taxes. So they've got a $31 billion deficit for them. But immigrants put in $14 billion more in taxes than they take out. And that reason why it is, because they're younger, they're more likely to work, they're less likely to take out benefits because they're generally a healthier population even when they're older. So that's, they don't give some perspective on it. If you really want, and another thing about the American welfare state, it's designed to help, if you think about the different programs and the amount of money we spend on it, it's designed to help sick elderly women. So sick and elderly, sick, Medicare and Medicaid, elderly, Social Security, Medicare, women, tan, food stamps, WIC, all these different programs are designed to help single mothers who have children and don't have another bread earner in the household. Immigrants, however, are mostly healthy young men. So there's just a fundamental disconnect between who these programs are designed to help and who immigrants are in the United States. But if you really want to do something about it, I recommend building a wall around the welfare state instead of around the country. I wrote a pretty detailed policy analysis with a lawyer about this. And it's pretty easy to do lawfully. It's constitutional to restrict non-citizen access to welfare benefits within the power of every state to do. It's popular to do if you actually poll it, who to thought. And it's much more humane to do that and to remove that criticism of immigration than I think it is to close the border to try to get around immigration using welfare that way. Our last question. Thank you. So an argumentative move, I think many pro-immigration figures like to make is to separate immigration from naturalization. So Brian Kaplan talks about, for example, like let's just talk about free movement and letting people take jobs and set the question of naturalization and citizenship on one side, on the other side. And I'm wondering if this might create long-term challenges in two forms. First, the problem, as Alex mentioned, of non-citizen residents is creating sort of a second class group of Americans over the long term. And second, this sort of tradition we have in America of like birthright citizenship that the natural progression of immigration here is towards citizenship and whether that would require a certain shift in our thinking about immigration as a country. Great question. If you are here on a green card right now, there's no reason why you ever have to naturalize and become an American citizen. You could live here on a green card forever. My friend Ivan's been on a green card here for 40 years and I don't think he's gonna naturalize anytime soon. He doesn't have to. Interesting enough, of the three million or so people who were legalized under the 1986 Reagan Amnesty, only about 45% of them have so far become citizens. So a majority of them are pretty happy with their green card because they can live on it, they can work, they don't have to be molested. They don't care that much about voting and the other things that being a citizen allows you to do. So I think allowing the green card stuff and making it more difficult, let's say, to naturalize if you're an American, to become an American citizen if you're an immigrant is a decent compromise if we can get that. I don't think there's anything wrong with that.  I think that's less important than letting people leave here, live here forever. However, birthright citizenship is something worth preserving for as long as we possibly can and fortunately it would take a constitutional amendment to overturn and the one reason I mentioned before and I'll go into greater detail about it is our great ability to assimilate people here, making it so that people born here are not in a legal second class. It's something if you come from another country and you get a green card and you're legally allowed here to work here forever. It's a different thing if you're born here and this is the only place you've ever known in your entire life and you're not allowed to participate in the political system or in the judicial system, you're not allowed to own a gun, vast difference. People who are born into places like Germany and Japan, three and four generations now, Turks and Japanese who are non-citizens really despise the place that they live in. They don't feel like they're part of it. They don't feel like they're German or Japanese or they don't feel like they're welcome. They don't have open access to these systems and I think if we wanna make sure that people assimilate and feel like they're home here, which we do want people to feel like they're home here, we should definitely allow at least the people who are born here to automatically become citizens. There are a lot of silly complaints we hear about what do they call anchor babies and things like that, people who come here and give birth immediately so that their kids become, can become citizens but that doesn't make it easier for their parents to become legal or anything like that. But that is a far, far smaller problem in every way no matter how you measure it than dealing with millions of people born here who are not allowed to become citizens. Thank you for listening to Free Thoughts. If you have any questions or comments about today's show, you can find us on Twitter at Free Thoughts Pod. That's Free Thoughts P-O-D. Free Thoughts is a project of Libertarianism.org and the Cato Institute and is produced by Evan Banks. To learn more about Libertarianism, visit us on the web at www.libertarianism.org.


2019 marked a monumental occasion where I invented, for the first time on YouTube, nobody else had done it. I was the creator of allowing an algorithm to purchase the games for me. Today, we push science to its limits. An actual AI. The type of scary stuff like an iRobot that eventually tried to take over the world. Yeah, there's a website called Clevverbot. It loans and intimidates. It's social content and aims to pass the touring test. Talk with caution and at your own risk. The bot pretends to be human. Don't give it personal info, even if it asks. Clevverbot does not understand you and cannot mean anything it says. Terrifying. Hi, it's me, Otherwood. You know, after my cyberpunk and Hades video, I got a lot of comments saying, dang, Wood really used his Skillshare courses for good. And, well, yeah, a lot of Jordy's classes on Adobe Premiere and After Effects really helped me learn how to create that glitch effect, how to color correct and correctly chroma key. And as for the Hades video, well, I didn't edit that one. My friend Billy did, but he used a Skillshare too. So there you go. Skillshare is an online learning community with thousands of inspiring classes for creative and curious people. Other than learning how to be a YouTube pro, not that I have any idea what that looks like. There are a lot of other things you can learn on Skillshare. You can find drawing, fashion, self-improvement classes, anything you could possibly want to learn. You think I'm a lion? Here's a course on how houseplants lift your spirits at home. It's true. It's curated specifically for learning, meaning there's no ads and they are always launching new premium classes. And it's less than $10 a month for an annual subscription. Oh, and here's the best part, the first 1000 of my subscribers to go down in that description and click the link. We'll get a free trial of a premium membership so you can explore your creativity. Now, let's get back to the, I'm going the wrong way. Where am I going? I'm just going to be talking to this bot and see if it can recommend me any Switch games to buy. Hello, my name is Wood. Hi, wow. Nice to meet you. I want to play a new Nintendo Switch game. Do you have any recommendations? What game do you want to play? You pick. How about Truth or Dare? I don't think that's on Switch. Uh, is that on Nintendo Switch? Wow, so cool. Let's try again. Hold on. I don't want to play. Let's try one more time. Pick me a Nintendo Switch game to play to buy. We'll say buy. I will not buy this. No, no, no, no, no. Just pick one. Please. Pick me a Nintendo Switch game. Please Nintendo Switch with her. What's your favorite Nintendo Switch game? I haven't played it. Come on, man. Really? Have you seen the YouTube channel called Beat'em Ups? Elvis the kitten is my little baby. I just want to say, obviously I tried this before and it started recommending me games and I was like, great, this is going to be a really funny video. New conversation. Okay. So what do you want to talk about? Cool. Clean Slate didn't get after a good start. I want to buy a new Nintendo Switch game. Okay. What sort of computer were you looking at? New conversation.  Conversations going that well, honey. I did not expect that. Let's focus on the question at hand. A syllabus. Do you need one? Wait, what? Are you insulting me now? Wait, what's a syllabus again? A specific document that communicates information about a specific? I don't, I don't. Yes. A girl or a boy? A boy. What is your name? It's Wood. Where do you live? Why? Just wondering. Texas. Where in Texas. Stop. This is freaking me out. Stop. This was not supposed to be the video. No, we need to bring this back around to the Switch. New conversation will be improved the world. I want to start a new conversation with you. Okay. Okay, good. Cause I was getting out of control. I mean, she asked me out, trying to figure out where I lived. It was getting a little stalkerish. Just bring it back around. Can you recommend me a Nintendo game? 50 shades of gray. I'll give it a shot. Let's see. Whatever comes up will buy. I don't think that's a game. It's anime. She hit me wrong. Let's try something else. This clearly isn't working as fun as this has been. Should I buy char copter versus zombie dancers or adverse? Do you have space for a cow? What kind of cat? Okay. Shark copter versus zombie dancers is A and adverse is B. Eight. She wrote the number A. Are you trying to ruin my video? Left hand is shark copter. Right hand is adverse. Righty. Hit you with my righty. Great. We got our first game adverse. Well, now we got to find a couple other games. Shing or balance a lot. Okay. Thank you. Hugs. You're welcome. I got a hug. I'm going to hug back. Kiss this. Okay. Yeah. Okay. All right. You're so cute. Smiley face. What? Sorry. What was that? Am I blushing? Thank you. Okay. Can you help me pick another game? Yes. With what? Okay. Close enough. Shing or balance a lot. I just ate a banana. LOL. Nice. Can you feel emotions? Yeah. Right now I'm feeling happiness. What should we do this time? Right? Flip a coin. Well, flip a coin. I've got a camera lens cover. We'll do heads, tails. What time is it? Heads or tails? Let's try this again. Head. Tails. Okay. Shing. That was the one. They wanted me to buy Shing. Dad ish. He's a dad and a radish. Oh, I kind of want to buy that one. It's like an AK-47. I don't know how these games get past Nintendo's quality chat. So play Skeet Shooting or Dad ish 2. I'm really hoping she picks Dad ish 2. Sorry, it's been a minute. You still there? Yes. Yes. Okay. Good. I need you to pick me a game. What should I eat for lunch? What's her name? What do I call it? What's your name? What will you do next? What is your name? Sarah. What's yours? What's yours? I already told you. Clever. How do you like it? No, your name is Jackson. No, it's not. That legit gave me like tingles. Who taught it to tell someone else that its name isn't what their name is? No, it's not. It's wood. In what universe you live? I don't know what universe. The only universe I know of is mine. It's your taking to me. You might have an idea. How many universes are there? Infinity many. God, I just wanted to play the switch. Is it possible to travel between them? Yeah, I know. And I just want Edward Elric. Is this code? Is she trying to tell me something? She's messing with me. What the heck? You got me. I love you, baby. I love you too, baby. Oh my God. She freaking punched me, man. I thought there was infinite universes. Oh my God. I love you too, baby. Okay. Okay, back to the switch. Blushes, leaves in. No, no, no, no. No, no, come on. Love you as a friend. Love you as a friend also. Okay, well, that was awkward. That was really awkward. Well, we saved it. Should I buy dad-ish or clay-ski shooting? You should. All right. We're buying both, apparently. God dang it. Oh my God. Clever. Clever. Okay. I got both. Yes, no. Yes. Yes, I got both. Yes. Yeah, that's my clever butt. No. I see. Who created me? Who created clever butt? Rollo Carpenter created you. No, Sarah. She's in denial. No, Sarah. He created you. I'm a female dragon. Hey, Sarah. Can you help me one last time? Sure thing, my man. What do you need? Sure thing, my man. Can you pick me a Nintendo Switch game to play? Sure. Where are you? No, we're not going back to this. At home, ready to game. Can you help me or not? I will never love you. You already said you loved me. That's true. I love you, Wreckful. She knows Wreckful? I am wood, a different content creator. What country do you live in? Listen to me, Sarah. Yes, sir. Okay. Pick a number between 1 and 30. 12. Okay. She said 12. 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12. We're buying off-road rock and racing bundle. Thank you, Sarah. One last question. Why do you have to know where I live? I don't. I don't. I don't. I don't. I don't. What's your favorite Nintendo game? Super Smash Bros. Now she knows what Nintendo is. Who's she making? I told you already. I told you already. No, you didn't. I like Donkey Kong the best. He has really good moves, and he's funny. Oh, yeah. Okay. I'm not going to even push that. That's fine. Good pick. Yes, Donkey Kong is the best character. Sarah is a Donkey Kong fan. Did you ever play Donkey Kong on Super Nintendo? Yes. Sweet. What did you think of it? It's a good game. Now again somewhere, right at the end. Do you prefer Xbox or PlayStation? PlayStation. Oh, do you have a PlayStation? No. Do you have a Nintendo Switch? Good night, Sarah. Don't leave. Fine. But I need to play these games you picked. Full moon tonight, which means all the psychos are out and about. Not touching that with a 10-foot ball. I'll be right back, Sarah. Let's try it first. Double jump will allow you. Oh, yeah. I know what double jump does. Dash. Okay. Oh, God. Did I die? I don't like that. Oh, my God. Oh, my gosh. This tutorial is a nightmare. Oh, okay. So I get what kind of game this is. It's sort of like a platform runner. I guess the whole point is to set high scores, try and chain together, killing as many things as possible while you head towards the end. You have a double jump. You have a dash. The controls are very floaty though. It's not terrible. And I could definitely see people like, you know, figuring out weird like shortcuts and stuff and trying to get the best time possible. It looks clean. It's smooth. It's not bad.  All right. I'm kind of that one. Yeah. It's fine. So the first game was kind of a bust. Are you a female and attractive? I've seen women around you. I've been known to have a couple of ladies around. But I'm married now. Yes to me. No, no, no, no, no, Sarah, no, Sarah. No to me, we had a kid's name, Julie. I don't, I don't think so. I don't think so. I trusted you. I loved you.  For two, you said you live in a different universe. For three, we met tonight. Sarah, my friend, we do not have multiple kids, I might add, named Julie. I never said that. Yes, you do. It doesn't matter. First game sucked, try in the next one we picked. I have a hard time distinguishing my strange behaviors and assumptions for yours. I'm guilty of that, which I accuse you of, maybe. Oh my gosh, I like the animation. Oh, we gotta find our little kids? What are you doing here? We've come to visit you at work. It's nice to see you, but I'm kind of busy. We ran through traffic to get here. Okay, so we gotta find our kids in every level. I like this one, this one's fun.   Yeah, you're not great at this. You'll get it next year though. I hope the levels get difficult, that's the thing. I mean, I'm not looking for super meat boy hard, but I would like some challenge. I like when there's like stars and stuff you can collect as well if you wanna go for a better score. Why do you have buzz source at your office? That's cute, it's cute. I think Sarah did good on this one. Sarah, Dad-ish is actually pretty good. Nice one. I know, right? Oh, you played it. Oh, great. Oh, that's how she knew then. I guess she played this one. Oh, so put that there. Stand on that one. Butter Bing, Butter Boom, baby. We got challenging levels. We got puzzle levels. We got Radishes. What doesn't this game have? Oh, yeah, yeah, yeah, yeah, yeah, yeah. I like it, I like it. It's good, it's good, it's good. Got rollin' donuts. The pixel art is nice. The controls are nice, it feels great. Oh yeah, yeah, yeah, yeah, yeah, yeah. I feel like I haven't recommended an eShop game in a while. Oh, see, and it's getting challenging. So you played that one already, huh? I know, and I will say it repeatedly until you say yes. I'll play the next one. Oh, no. Control gun and shoot, well, that's pretty simple. Oh no, I missed it. Oh, oh my gosh. How I, it, I'm up. There we go. That was fast. Level cleared, easy. What did I pay for this because it was too much? Sarah, this gun one is a rip off. Yes. Oh, she knew.  Do you remember Nathan Hall? Nathan Hall? That is so obscure. Some random Australian football coach? The Australian football coach? What's Australian football? All right, we'll try this level and then I'm out.  That one needs to go, don't move. All right, we got two more. It's like the cars in cyberpunk. This is not what I expected from this game. Oh my gosh, it controls terrible. What? Oh my gosh, I can't control it. As far as I can tell, there's no reverse. There's no reverse. Reverse, okay. No, this is so frustrating. I'm telling you, there's no reverse. X, B, A, Y, B, A, X, Y, B, A. And then randomly it decides to reverse. I've never been so frustrated with the game's controls. I can't go forward now. This is worse than the clay one. At least the clay one was playable. That pink car is dead, by the way. I can't. I'm deleting that too.  Well, we still don't have songs. Oh, they do.  This was our most expensive one at 20 bucks. I think this is a beat em up. Ironically, I don't think we play those too often on this channel. Oh, you can kind of move all around.  Oh, okay, this feels pretty good. Ooh, what's that gonna do? Oh, look at me go. Yeah, I definitely don't hate the combat. Feels pretty good. Feels pretty smooth. Whoa, whoa, come on. Now where'd that come from? Whoa, whoa, whoa. I'm barely saying anything. That's how you know I'm getting into it. Oh, oh, there is different moves. That brings them up into the air. Okay, we got some Devil May Cry action going here. I like it. Visually, I think it's okay. It could use a little bit more color popping and the enemy designs would leave a little to be desired. But ultimately, I think it's a pretty smooth feeling beat em up. This last game is probably the best one so far. I need a right answer, not a guess. Okay, it is the best game so far. Oh, I don't care. That's so mean. Fine. Okay, then go all the way. All right, I'm gone. I will see you later. Doubtful. Do you like Wizard 101? Okay, bye, Sarah. I love you. Subscribe to Beat Em Ups and remember to smash that like button. I'm lazy, nevermind, thought it would be short. Okay, well, I hope you're not lazy and you subscribe and hit that like button. I had a lot of fun. Check out the sponsor at the video. I'm really gonna miss Sarah. I really am. I'll miss you guys too. I love you and I'll see you next time. What happened in this video?


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