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Experts talked about the latest research into the development of a Coronavirus Vaccine, as well as safety concerns and the need for global participation. As of this morning, there were over 27 million global confirmed cases of covid19, and 892,000 deaths. Point 3. S. We have six million confirmed cases and we are approaching 190 thousand deaths. We have seen significant economic disruption to businesses and families, and normal daytoday activities have been vastly altered. Leadingexperts experts have said we need a vaccine, which is why the topic is so critical. We will also discuss the lessons that we are learning now in developing a covid19 vaccine, and the implications for if used future Vaccine Development. We have a short amount of time and a number of really terrific speakers, so why do we not get started . Mark, why dont we begin with you. About vaccines under development from pfizer, astrazeneca, in partnership with the university of oxford, all of which are in phase three Clinical Trials. You have been working on many fronts working to establish a viable process to fasttrack safe and effective vaccines. Can you fill us in on what that looks like and where do things stand. Mark thank you. First off, thanks for bringing us together, this is a great group and a timely topic and a reminder why Research Americas mission is important. It is important to see the amount of research and develop and progress happening on covid19 particularly in the area vaccines. We haves mentioned, been working on this for a while. You look for accelerating therapeutics or a topic like that, and a lot of the information that we have put together on what has happened this time that is so different because of the very large health and economic consequences of this pandemic. Essentially, we are moving faster, and with multiple vaccines at the same time. Seven are backed by the federal government and more are in development in china, europe, and other parts of the world because of the high burden of the pandemic, not because we are necessarily cutting corners. Fromhas changed is moving a long and linear, and uncertain , and questionably funded process to one that is hyper parallel with clarity, and every channel needs to succeed to get to a safe and effective vaccine. That includes clear guidance on what needs to be done from a regulatory standpoint, fda, and other regulatory agencies came on early on with specific guidance on what was expected for a vaccine and preclinical testing. The fda issued a detailed guidance that would recommend people who are interested in this talk it to take a look at the process. Further Clinical Development process, there is clarity on what is needed to be demonstrated in terms of an impact on reducing the severity of infections, and the number. It needs when nickel trials of a certain sample size to have safety effects and in a bigger population. The nih and others have come together to develop a Clinical Trial network that is enrolling large numbers of people in these trials, so the early trials get moderna, and pfizer, and coming soon astrazeneca. I have already started to enroll several more in the next month 30,000 orpecting more. Many of these are already up to that number. Pfizer is always in the set already in the second round for this two dose vaccine. That is the first vaccine they are developing. Clinical trials are happening at an unprecedented pace. At the same time there is a lot of early investment in manufacturing a vaccine at scale before that we know before we know that it works. The Government Agency that oversees these countermeasure and Public Health emergency activities going in jointly with many of the manufacturers to build capacity here and elsewhere and have literally tens of hundreds of millions of doses of each of these promising Vaccines Available by the time the Clinical Trials are completed. And, theres been a lot of discussion recently about whether this means corners are being cut. Based on what i have seen, the answer is no. A very substantial planning process. You get all of these critical steps done at the same time. Looking ahead, there are important decisions coming based on the evidence that is being developed in the Clinical Trial. The fda has made clear that a vaccine is not going to be approved, even for emergency use, and less there is a clear standardat meets that of effectiveness. Also, no clear data and tens of thousands of patients who have been tested of a clear safety problem. Safetyy that, drug collection will continue for a couple of years as the fda often does with vaccines to make sure that there are not any late issues. So, how fast could this be done is in the subject of a of debate s,ong scientists, political and others. It seems unlikely that we will have any trials complete where that level of a of evidence is available before the election. People should have a clear understanding that the people involved in this effort have a transparent process Going Forward. Before the fda approves the vaccine it will clear that it has a meeting of its independent advisory committing. Before that there will be data or ported from the company that they put in their application for emergency use or otherwise. It will be reviewed for the staff and what they think of the data and that will be a public discussion of what it all means for the basis of any further decisions. Emergencyhasized that use for a vaccine is very different for emergency use for a treatment like cosmo convalescent plasma, that is the treatment where we have seen it used in any other conditions and thousands of patients with serious covid infections. It is intended for people who are hospitalized and seriously ill, not a healthy population. Because they are not many safety concerns, it is a different kind of standard than what we are talking about for a vaccine. Very important developments over the coming weeks and we will see how fast the trials can go in terms of not just enrolling patients, but a declining rate of covid in many parts of the country, a good thing for Public Health. It means it might take longer for trials to complete, and we will see how effective the vaccines are in reducing the number and severity of infections. Running people who are the top the trials, they will be looking along the way to see when there is a signal that meets fda standards. As long as we are following verily very clearly laid out approach and a defined that fda experts and the center have laid out to get us to this point and help us move forward, we do have a very promising outlook for vaccines. That said, we are weeks to months away from having the more definitive evidence and even then, as we may talk about during the panel, it will be sometime before the vaccine gets out to everyone. We might be starting with high risk or highpriority groups like military personnel and medical responders. And, we might go out from that as the evidence accumulates and we have more supplies available. I are at a critical time, but think we will begin this phase of uncertainty and continue to learn for a number of weeks to come. Donna that was a terrific overview, and we will pick up on a lot of the things we talked about. Paul, i wanted to get you into this conversation on the topic of the timeline. Since the early part of the year we have heard 12 to 18 months, and we are approaching some part of that and this expectation that we will have some kind of a vaccine or candidates available as early as even november or december. Can you help us understand what this timeline means for Traditional Vaccine Development . What could we expect towards the end of this year, and what could we expect in q1 or middle of next year . And is this realistic . Paul i am happy to make any prediction even though as long as you dont hold me to it. Mark covered a lot of this. The average length of time it takes to make a vaccine is 15 to 20 years. Because we do it so carefully. You go from preClinical Trials and thenredoes trials you get the big definitive placebo and control and 30,000 person trial which is the only way you will determine if it can be done safely. What has happened now is that government has taken the risk out of the pharmaceutical companies. We have been able to coalesce because the government said we will take the risk. We willpay and massproduce this vaccine without knowing whether it is safe or effective. We are willing to throw away doses if it is not effective. No company would ever do that, which is why i think that on the one hand, i am not worried about this timeline initially. We are doing big recalls. If we are doing what we are going to do which is a 30,000 person trial, that is great. Conjugate pneumococcal vaccine was a 35,000 person trial. There are two other thing standing in the way of releasing a vaccine that would be less than safe and effective, which who are charged with looking over the vaccines. That is good. And then if he was treated this true to his word if during that oped, he will speak the advisoryr the fdas committee and that is another group of independent resources researchers not associated with the government or pharmaceutical injury. He will give you their honest opinion. None of that worries me, i think it is good. One however has to be concerned about a few things. One is that this is not a standard licensure procedure. It is likely to go through emergency authorization and that is looser. The languor the language that surrounds emergency authorization includes phase phrases like maybe. The second thing you worry about is if you look at what happened with hydroxychloroquine or convalescent plasma, which were given to those who were already sick, that is different in that they are being given to billions of people who are generally going to be healthy and young people who are not likely to die. You want to hold them to a High Standard of safety, and i worry in those two cases, that you saw to donce on the fda something that should not have been done. I think neither of those should have been approved for use. So people that are worried about whether the vaccine would be approved for use under a luzern ndard, so much so that looser standard. So much so that the pharma coals the pharmaceutical industries wrote a letter saying that they will be held to a High Standard of safety. They should not have to write that letter, that is what the fda does, stands between the American Public and the pharmaceutical injury history to make sure industry to make the mayor can people feel safe. They say with that letter that the fdas unwillingness to stand up against an administration under pressure. The fact that china, russia, and the United Kingdom might come out with vaccines before we do. I think, as it stands between hiscommittees and commitments on paper to make sure that we hold these to a standard, i feel good. But you are a little worried, that is it. Nobody am a worrier, but else is, but it does worry me a little bit. Donna just a followup and i will bring others into the conversation as well. Is it a guarantee that we will have a covid19 vaccine . Many scientists have said that science are hard and you have been involved in science for many decades. Are we guaranteed to have a vaccine based that has high efficacy. Paul no. There is no guarantee. We have this elusive difficult to characterize virus. This coronavirus that made a statement to the human population and done things you have never predicted. That is an envelope virus rages through us and who wouldve produced predict that. They had it has post infectious phenomenon, i know no other virus that does this. Influenza also kills older people, but 10 deaths are in norse Nursing Homes and here it is 40 . It appears that all of the stuff all organs are at risk to a heart attack, stroke, liver disease, kidney degree kidney disease. Weeder meeting that challenge and vaccines with mrna adenoviruses that have never been used as commercial products in the United States before. Is there going to be a learning curve . I cannot imagine that there would not be. Things that we knew now we will learn. Things that we wish we knew now, we will learn. There is no guarantee, which is why we do the trials. Donna we will go back to the discussion that is needed the amount of evidence needed. I wanted to pick up with the point that paul brought up that is there is a lot of different kinds of technology right now that is in developments that has never gone all the way through to commercialization. The first, what has happened in the past has brought us to this point so we can accelerate the covid19 vaccine with these new technologies, and how do you think about that Going Forward. Are we testing things that you anticipate will have treasures for other vaccines . What led us to that point. That is a great question and very broad reaching. Let me first say very clearly that we look upon vaccines somewhat to different baskets. One are the vaccines that would be used routinely, in particular safety is very much our area of concern. Infant vaccines are typical infant vaccines are examples. Is a public vaccine Health Emergency of International Concern vaccine and it is a different ballgame and handbook. We have thought about and worried about a pandemic like we onceeeing now because before, a century ago we saw it with an influenza vaccine. And so we know that it can happen. There have been a few signals that stimulated dress rehearsals. 1976 when i was a young assistant professor and there was a worry about a swine flu virus pandemic. Rehearsals inss my view began seriously with the Ebola Outbreak in west africa, which devastated the health care infrastructure, destroy the economy, and when cases started to appear in europe and north america, it became very clear that all of the consequences and we began to worry more. , 2014 through 2015 epidemic came the birth of the coalition for epidemic. This innovations. And why its moments was kurt it was created, first science to make vaccines rev up. Ly we have seen a number of milestones put to use. And, technology is we call them plant farms, where one can take the sequence of a virus, key, andthe antigen use that sequence to either express in live virus vectors or to make a purified protein, or vaccines,cleic acid all become possibilities. Each one of those is potential each one of those has potential. There has been a lot of background work on these platforms. Part of what we and other groups have been doing is monitoring and looking at what might be the next dangerous organism. In 20022004reak was a harbinger. The mers is the harbinger. Those are both other beta coronavirus is. And hero comes this and here along comes this beast of the virus in east asia. Very quickly the sequence of that virus was made public, very byckly that was utilized various vaccine developers. On the way, one of the things that was done was a modification of the virus. So, this is work done at the surf center, modification so that the prefusion configuration becomes stabilized, which, theoretically enhances the stimulation of neutralizing antibodies. s moment, because they are ways to quickly make vaccines. The mrna has a theoretical advantage. And it has been shown from the sequence to first inoculation and in just about two months, and also, the possibility of a largescale manufacturer. But, these are not from the , superc perspective perfect vaccines, even if they are faced and highly protected. They require two doses, a special cold chain, these are not showstoppers. Aree are solvable, but we so far along where we are very close to having very good vaccines. Last point i would make is that this is truly a global problem. Vaccine not only for the u. S. And europe, but we have to have vaccines for the entire world, because as long as there is a reservoir of continuing transmission, the homeland, the u. S. Homeland, the rest of the industrialized countries are at risk. Donna yes. Ruth, i want to bring you into job, and mike today nice laying out the potential for these different technologies, how quickly you can develop the vaccine. We have the mrna platform as he described. What this means is that we need a robust profit process for ed evidence generation and Clinical Trials where we can determine wicks vaccine is the most which vaccine is the most effective. I know you think a lot about these kinds of issues. When we are looking at enrolling different patients, pregnant elderly,ildren, the right now for covid19, this highly impacted patient populations like minority communities. How important is it that these trials are representative if we can get the answers that we need . Either for office authorization and insurance . Ruth, and you are on mute before you start to speak. Ruth thank you for the reminder. I think you bring up a really important point, and i think that all of these considerations are not the same, and i think we should start care and say that pregnant women, children, racial and ethnic minorities, and there are overlaps in those categories. Those are not all the same and i do not think we should treat it and lump those together as we think about Clinical Development. In thinking about this panel, i have been thinking a lot about Lessons Learned for the future and how we can think in this time do will inform our future Vaccine Development, and one one of the Critical Issues will be around inclusion, and one of the legacies is going to be around inclusion. Certainly, this is not a new problem. Speakinge problem particularly about racial and ethnic minorities having a disproportionate burden of Infectious Diseases and nonInfectious Diseases is not a new problem. And lack of inclusion is not a new problem. Are our focus on this, and efforts to make this right and our efforts to make this right because this is Critical Data for us to think about how we deploy vaccines, because we do have a number of vaccines. I think i am by nature an optimist, and i actually think we will have vaccines and we will have more than one. But, you think about how to best use these vaccines. We really need to know how they work and populations, and we really need to be able to build trust as we are doing the trials, which is abridged to having trust when we deploy vaccines. Would say that for all of the populations that we consider, we want to think about risk, benefit, different platforms, what we are trying to prevent in terms of vaccination, are we trying to prevent acute disease, or severe disease. Are we trying to prevent transmission, which i would remind everybody, we are not looking at in any of our u. S. Trials for certain, that is a bit of a jump in our thinking, although certainly we have many pediatric vaccines for example that have prevented transmission to others. So, i think those are all issues that will need we will need to think about as we continue with the evaluation of these vaccines, and i would also say , as clinical investigators and policymakers, we have to walk the talk. Everybody, everyone has embraced the notion that we have to have diversity in trials, but we actually have to continually monitor and think about if we are not hitting our target or doing what we want to do, what are the barriers and how do we overcome them . Saying,rom what you are just a followup, are you comfortable with the level enrollment of enrollment you have seen around diverse population . What do you think needs to be done . L i think ruth i think there are the practical issues, and i think there are the trust issues, to be honest. I think around the practical issues, we have to remove barriers. And ie of the things, think all of my colleagues have highlighted, this is not business as usual. Two, we have resources for Vaccine Development the likes of which none of us have ever seen. We need to use those resources for good. So, if there are barriers to enrollment that are around access, somebody does not have a car or transportation to get to a vaccine center. By all means, there should be mobile vans that can go to where the people are. If there are populations that and have and rural different ways of doing things, one of the things that i think is really important is that we need to listen both to the population and actually to some of the really experienced clinical investigators who have with their careers working disadvantaged populations, to ask them both the populations themselves and the investigators, what do they need. That is a very sort of pragmatic answer. On the others there is building trust, and that has to do with quite frankly having members of the study team who racial and ethnic minorities so that people can feel comfortable that there are people on the team that looked like them and are part of their community, and it also has to do with going to Community Leaders to engage and support. Donna absolutely. I think building that trust in an ongoing way is really important with local communities. Will if i could turn to you, for many of the programs that are well underway, the government has borne the full risk, which is why we are able to accelerate so quickly, and we know it takes a tremendous amount of resources to bring any vaccine to the we talk about how it takes 1 billion, 1015 years to develop a drug. In a pandemic, we rally around significant disruption, it is solved, and we move on to other issues. You recently coauthored a paper in Science Magazine along with gary and others around the topic of how do we provide the right incentives, not just in the middle of a pandemic, but post pandemic so that when we are confronted with another pathogen we are prepared . Do you see those incentives happening now . What do you think about them Going Forward . Thank you and good afternoon. Thank you, everybody else. It is an honor to be here with you. Mentioned, and my father, and i authored this paper together. Think a little bit about the regime we have in this country and how it is applied to the current efforts to develop and disseminate a vaccine, and the opportunities it provides for future crises. In this country, our innovation regime comes out of the constitution. Eight isight, clause for copyright and that covers one part to develop vaccines, the innovation incentive. You need to create an incentive for people to develop and transmit and manufacture all of these different vaccines and therapeutics. The other part of the problem is that patents create that incentive by creating a 20 year monopoly to the owner of the patent. While you have reduced it to practice and given public disclosure, which is the tradeoff for that monopoly, we get to an issue dr. Karen braved inclusion. Once you have received the innovation and exchanged it for a monopoly there is no inclusion because you are going to get monopoly prices. The problem in a crisis like this one where anybody can get infected, where there are huge issues toward vaccinating everybody, we are at a disadvantage if we rely on the patent system. I, naval, my father and talked about what alternatives we could use. These alternatives should not be unfamiliar to people in pharma. It is an alternative they use every day. It is a reward system. Where you want to create an incentive to develop, innovate, and disseminate, on the other hand you want to create pricing as close to margin profit as possible. Government acting ideally through the g20 could create phaseof reward for poo one, phase two, and phase 3 distribution. We could have the best of both worlds. We could have the incentive to innovate as well as pricing close to marginal cost. In infectious disease, where you have Huge Positive externality whenever you treat your marginal patient, that is a surprising mechanism that is superior to the patent mechanism we have now. Si something dr. E something dr. Levine said. We are, in the United States, a reservoir of continuing transmission. If you look at it, we need to collaborate internationally so that we can create a regime of incentive and apply it internationally. You can do it with the wealthiest countries creating a reward pot for the innovators, and then we need to have international distribution. What are we doing now . I think there are certain things we are doing now that are the wrong way to go. For example, trying to pick winners and losers through Government Brands to specific manufacturers. I do not think that is the right way to go. There used to be a time with an r next to their name did not pick winners and losers. I do nothing we should pick winners and losers, but the strategy we have proposed does not do that. I think what we do is let the cream rise to the top, incentivize via reward system, and get as close to marginal price as positive so everyone can benefit from the innovations the public funded. Well, i think you raise an important point. What do we need in a Sustainable Way to continue innovation well past the peak of the pandemic . What we have seen, and i will turn to gary, is we have seen tremendous collaboration. We have seen Companies Come together in different ways, potentially that will continue Going Forward in the future. We have seen philanthropy in the private sector come to bear on Clinical Development in ways we have not seen before, or certainly not at the scale. When you think about the ideal system, and we will point out part of what that could look what doen we go forward you think is the ideal role of industry, private sector, philanthropy, government in really having a cohesive Vaccine Development ecosystem . Well, thank you. That is a really important question and one that i have been involved with since my early days as a nih with tony, actually, developing the Vaccine Research center. I think wills comment, and the piece we wrote together, way,ights the fact that when we approach these outbreaks, we basically have a fire drill when there is an emergency. We have these boom and bust cycles where we invest in vaccines and Vaccine Research. Us to builds for a sustainable and effective deterrence for infectious disease, and i would argue for all of human health, we need to have consistent and sustainable funding. Mike, inays i think his comment, mentioned structural biology in the current vaccines Going Forward. When you look at the complexity of Vaccine Development, what it enoughi cannot stress how unimaginably complex this process is. I would argue of all the endeavors we undertake as human beings, from building cars to getting to the moon to whatever, developing new medicines, there is nothing more complex than developing a vaccine. It starts, you know, with things as sophisticated as structural biology that mike mentioned, it goes to virology, immunology, human health, it goes to manufacturing technology, it goes to ethics, it goes to the way societies live and except accept information, and then that diversity of the human population. Think about when we were talking about vaccine trials. Think about going out in the real world. We are doing trials and we are not doing trials with a control group is identically and genetically matched, kept in the same environment as the control group. We are dealing with populations where people are walking around, some have underlying cancer, some have colds, some have diarrhea, and you are doing a trial in the real world were all of these people are exposed to the vagaries of normal life. That is why we do a 30,000 person trial. Perspective the most important thing we can do, and i think what we really need to begin to implement in a serious publicprivatel, partnership where we find mechanisms by which we can continually support these efforts, where we systematically monitor new bio threats, where we develop better diagnostics so that we can catch them early, where we have preventative measures that are in place that guard against the most likely threat in the shortest period of time, and we can deploy our knowledge about vaccines in a way that leads us to the kind of fruitful and protective countermeasures we need. The only other comment i would make is several have said that, and tony said it earlier, that it is completely unprecedented that we have been able to develop a vaccine in the period of time we have. A lot of people should be congratulated for this. Both from the industry and from basic science, the nih, cdc, fda, but i think we should also forget, ishould not the reason we are able to act this quickly is these vaccines in start with the first sars 2004. It started on this road of developing effective vaccine for coronaviruses and we developed a prototype that could not be tested in 2004. Andhen progressed with mers that mutation mike was talking about came out of mers research. That was then applied to the second sars virus. It shows you consistent, longterm support from the Research Enterprise and acrosstheboard in technology and Clinical Development and Public Health. That is, i think, what we need to focus on for the longterm. I think to that point we have the potential to bear the fruit of the labor today for the future, many decades from now. Just as you pointed out what we are experiencing today started with sars, but as will said earlier, we need that sustained funding. You know, there are pressures right now that we have been talking about, hearing about, and i want us to go back to that and go back to the conversation we started with with mark and paul commenting around what do we need, from an evidence perspective, that will make the public feel confident with a vaccine if it has been authorized under an emergency use authorization . What is that bar and what is the second bar in terms of license ship . Be concernedwe ca or are you confident . I am confident there are people with the knowledge making clear we need to take this vaccine emergency use or broad use really seriously. I think the good foundations we have to build on is that fda have been pretty clear about what is needed to get their recommendations for approval for a vaccine. If you are interested, we have a followup event on this topic on thursday with the leadership of the center for biologics where they will talk about this exact topic. If you look at what they have said, it is going to be very different than the emergency use authorization standard for Something Like remdesivir or convalescent plasma. This is a reminder that the standard, in general, does not require definitive evidence of safety and effectiveness and that is why some of the treatments that have been approved so far where there is not any evidence of substantial safety problems, there could be evidence of benefits, why that has been done for these treatments in seriously old patients. I would feel better if we had a better Evidence Development system in place for those technologies just like we do for vaccines because of all of this parallel effort that has gone into supporting Vaccine Development. In contrast, we still do not have good randomized trials of convalescent plasma and we would like to learn more about some of the other treatments that have been approved for emergency use and develop it. Frankly, things are not going as quickly as we could. I would like to take a lesson out of the playbook for vaccines to set up some simpler, more compelling Clinical Trial networks for the other therapeutics. But back to vaccines in particular. I think what would be very helpful is for people like those in this group to understand what exactly the biologic center is looking for when it comes to a decision or recommendation about emergency use authorization or broad authorization for a vaccine. I think the more thoughtful people can take a look at those standards and help make the American Public more aware, hopefully we can address some of the challenges that start coming with this very political, predilection environment we are living in. I think this is not just an issue between now and november 3rd, but after the election there will be a time when we are not sure about the results, or a transition. There will be the next few months that will be very important for vaccines where we will have more evidence, where we will, potentially, begetting into distribution and hopefully distribution that will reach at risk populations like the communities of color and others. For that to work, it is not just a matter of working out the technical details, it is a matter of working out the reasonable places for Public Confidence basis for Public Confidence. I think all of us here who care about the issues and viewed as having some relevant expertise to the issues of wit to the American Public to spend time at what would be involved in emergency use authorization. What would be involved in approval and making sure we are comfortable with that. We have every other piece of this Vaccine Development effort proceed at an accelerated pace. This other key element, public understanding, expert understanding, and communication is another key part of that parallel process. We need to bring the American Public along and the only way to do that is have a process that works. That is why what industry has done recently, they want to be behind a regulatory process, people like me and other former commissioners set along the same lines, we need more people willing to take a close look and try to get behind an effective approach for Public Confidence in the vaccines that will becoming and the decisions, and support, about them. Yes. I want to bring ruth in as well who has a comment on this question. Tee up a question, safety, data, and monitoring. What does that mean Going Forward for the public trust . Ruth, you had a followup question for this and you are on mute again. Sorry about that. I just wanted to make a comment about public trust and communication. Paul may have two things to address next because im sure this will play very much into things he is interested in. I think that, regardless of the extent of evidence we have or license, the of his example is we will not know much, if anything, about the durability of protection. There may be other things we do not know. We will not know, even with 30,000 person trials, there may be weird side effects we do not detect in initial trials. Truef these things are when we are licensing vaccines and other context, but it will be true here also. I actually think this is sort of a national teachable moment about vaccines and i absolutely i saw in the chat box somebody mentioning the New York Times vaccine tracker. I was really encouraged. Anyone listening who has not gone to that website and looked at that vaccine tracker to look at it because it is an extraordinary piece of education for the general public about the kinds of vaccines we are evaluating. But i think it is also really important when we do efficacy trials for the public to begin to understand and explain in ways everybody can understand, what are some of the statistical tests we do . Boundhe fda says a lower on a confidence interval of 30 , what does that actually mean and what is the point estimate mean . Vacciney something, one is 70 effective and one is 65 effective against endpoints and intervals overlap, are those different . I think we really need to think more about how we can educate the public and thinking about the legacy of this after this pandemic is over. If we can use this time to teach the public more about vaccines, we will be better off for this problem in future problems. Public education is going to be critical. What the public understands is length of time. They understand the vaccine isnt of element for a period of in development for a period of time. [indiscernible] launchedaccines were they are not launched because you know everything. They are launched because you know enough. You have enough safety data, enough efficacy data to say that the benefits, as we understand it, outweigh theoretical risk. Beo think there is going to a health decline. It is understandable. You have a skittish American Public. Has the language that surrounded this process has been scary. Finalist, who is the guess is that safety guidelines were being skipped. You have an administration that was willing to perturb the science. The food and drug administration, the weather center, it makes me nervous. Personally, when you see phase i trials being published, which involve 10 people or 15 people getting the dose that is going to be the final dose, and you have the companies talking about how they could make tens of millions of doses it is a little nerveracking. You do not feel, at some level, the humility that should be part of this process. I know you mike and move forward in these processes. They give secrets up slowly, grudgingly, and with a human price. I worked on rotavirus for 26 years. That virus had been worked on for four decades in animals and people and then there was a thatne in the late 1990s caused side effects. We have been working on that vaccine in animals and people for 40 years and that was a surprise. We have been on this for one year. You have to be humble. In terms of explaining to people, and ruth said this, once you have data in hand you can try and explain what you know and do not know. You can say you have given it to 20,000 people safely, but that is not 20 million. The safety datalink by the fda that can look for rare adverse effects. As ruth said, you know the vaccine is effective for a certain length of time. You have to be really honest and transparent about what you know and what you do not know. If we do that, it is going to be a slow climb up the hill, but i think we can get there. Mike, are we going to have an annual Coronavirus Vaccine . Do i need to prepare my children for flue shots and coronavirus shots . I do not know that. There has been monitoring of the , what emerged in china, and that would be one of the things to watch. Thisul mentioned earlier is a novel virus. Coronavirus that does not strikingh seasonality. Commentadd, if i may, a to the last discussion and that nts to bell of our te open, two points. There is a part of the population who said they will not take the vaccine. There are some divided into one group that is fanatically, conceptually antivaccine. Their mindsot be will not be changed based on interactions of the measles vaccination in past years. The other two are hesitant. They see smoke. They wonder if there is a fire, but the truth is even with well done trials, and we do everything right, we followup and there are unexpected things that happen. We need to look back in the other dress rehearsals. In 1976, 40 million americans were immunized and rarely, very paralysis put a terrible legacy, but it is part of our legacy. We just need to be very, very careful. We need to be as open as possible. We also need to recognize there are folks out there who are planning to toot their own education of the population. Comment like pauls about humility. One thing missing is a soothsayer, someone to look into the future. Something we cannot do. Think that probably says a lot which is the uncertainty we are dealing with right now. Why dont we turn it over to questions coming in from the audience . Someone was interested in wills futurel for how we lead Development Efforts toward pandemics. Interested in your perspective and critique of the barda led approach and what you have proposed which are rewards and incentives. The question is, is there a key difference with the patent structure . Is it possible to think about investments by governments through the kind of arrangements that are closer to marginal cost . Essentially, what your paper outlined, how do we move forward and how do you think about this current approach in terms of how barda has invested in Clinical Development . Interesting and you will have to pardon me if ive year toward the legal i vere toward the legal because that is my background. It delineated and created this monopoly issue. The constitution provided a potential solution. Back in the days when people were complaining about the price of hiv and aids medications and these were patent protected drugs and should just be given to patients. There is a solution within the constitution. You essentially pay fair Market Property this piece of held by a private party and, in exchange, you now own it. Post, wean do it ex are saying this is the full report. You play in the system and in exchange the public gets to own the intellectual property such that we can produce it at marginal cost. It is a merger of some of those concepts. What would be saying and this is not without gain to the pharma company. Example, as dr. Naval and my father were pointing out, people ramped up and made enormous investments only for the market never materialized. They took enormous risk and got nothing. You would know ahead of time this would be a locked in benefit. That is going to be your report. In exchange, the publics reward is pricing and post marginal cost for distribution. Conceptshese are the we are playing with. I saw some of the outset a question like, our these types of efforts underway . It has been suggested, but undertakenactually to build the reward system. Not transnationally and certainly not in the United States, but i think it would be a tremendous legacy of the covid19 pandemic to have the infrastructure for such a system for specific billion aided diseases delian delineated diseases. Let us continue down that line of thought. Gary, a question came in in the chat in terms of its impossible to realize privateglobal partnership in this highly competitive, fragmented, International Environment and what would be effective steps to bring us closer to that direction . Where we are not nationalizing Vaccine Development for example. That is a great question. I would say despite a lot of the heat we see, at least in the collaborationink does happen across borders. Inow, a good example is cite this only because it involves the company i work with with gsk,partnered two Different Companies into different countries, on a vaccine where sanofi is using the proteinbased Technology Production with had annct gsk used and hea agreement with barda. Here is an opportunity to proteinbased vaccine and also reduce the dose that you would have to give to any individual so you would have more supply and more effective. That needs to be demonstrated, but i think what the example shows is when there are aligned incentives where both parties can stand to gain and do things together they could not do alone, then those kinds of partnerships can happen. I think there have been fits and starts. I think we need to do better and if i were to suggest something new to try to address this kind disconnect we experienced with the current covid outbreak, i would say we need to have, essentially, the equivalent of u. N. A biological you we are going to focus on the virology,pidemiology, and do what is in the best interest for everyone on the planet. I think that can be done. I think you need to have investment there and will mentioned before the g20. This the Economic Impact epidemic has created investing a few billion dollars a year compared to the trillions this took out of the worlds economy would be a small price to pay. Aboutk we need to talk new structures. We need to think about new funding mechanisms. We need to recognize, and this is something that has not been ,et but should be top of mind it has not, in our lifetime, just been covid. Think back to hiv. Hiv was not a problem when i was a kid. There was no such thing. Now over 38 Million People have died of hiv. Sars, ebola,flu, they come one after another. This will not be our last show. There will be more. The time is now. Better, wen we do must do better and we must be thinking globally. In with a question came regard to trust in government over the last 40 years. That does not bode well for Public Health humanization efforts. You talked a little bit about this earlier. How can we communicate the benefits and risks to a very skeptical public . The second part of that question deals with what does this mean for pediatric patients and Adult Patients in terms of building that trust . Will parents feel comfortable vaccinating Young Children who have not participated in Clinical Trials . Thank you for that question. I think there are several parts to that. I would take issue with the notion of a skeptical public. I would go back to something mike said. Something polished talked about quite a bit. Who areer of people antiback source are a small ers are small, but vocal. They can be brought along. Is to beo do it transparent. To be absolutely clear about what it is we know, what it is we do not know, why we are advocating vaccination. What are the risks . What are the benefits . I think we need to think about that population by population and the conclusions we come to for elderly adults, younger adults, pregnant women, for children, that we will weigh all of those things. What i do think is true is probably not recommend vaccination before we had data from Clinical Trials and various populations. Widespread recommend vaccination. Aboutare people thinking how we can do those studies in various populations. People have been talking about pregnant women and when and how those studies will come. I think we need to generate data. It will not be the 30,000 person data we have from our big efficacy trials, but we need to have some of that information and i think we need to communicate. I imagine my colleagues might want to weigh in on this. I go into different direction, but i think that was well stated and reassuring. A q a weclose out with talked about what gives us pause, some things that are concerning, reassurances, but as you think about where we are right now what gives you hope . Where is your greatest optimism coming from despite the very challenging news with the everyday . Mark, why dont we start with you . What gives you hope . I think we are on the path for an effective vaccine and that is, in the end, going to help us get out of, and beyond, this pandemic and manage Ongoing Health threats. Hopefully things will end up better. I think we have also had opportunities to learn about ways to Work Together more effectively outside of the research context. There have been new steps of Public Health agencies working with health cour Care Organizations using workers to identify highrisk individuals. I hope we can build on that. In the area of research, there have been important collaborations. Most of the Clinical Trials undertaken for covid, they are not going to yield any meaningful result because they were not designed with enough power to begin with or because the pandemic petered out in a specific location. But we are seeing with the vaccine trials, other Trial Networks trying to do both supported by the nih and private supports trying to do fast trials with limited data collection, we can do a lot better at this. You have already heard from others about collaborations on developing distribution capacity, planning so that we are not just relying on thin and fragile supply systems. The point about planning ahead for creating the right incentives for new technologies, we may not do it in the context of covid vaccines this time around, but there is added support for doing market entry antibiotics that can be used against other Public Health threats with Global Public support. I hope we can make the most of the silverlining. It has been a burdensome pandemic, particularly in the United States, but i do see some good steps coming out. Not the least of which is getting a effective vaccine. Great. 30 seconds for everyone to close this out, what gives you hope, paul . I mean, scientific advances have allowed us to live 30 years longer. I think science is the way out of this. The dual prong of hygienic measures and a vaccine will enable us to climb out of this. I think it is going to be a clim slower climb. Mike. This discussion brings me back to the days of polio. At the National Paralysis where, as a kid, i would go around with things to collect money and people paid for a vaccine that trial. Ted in a massive there was celebration and that was everybodys vaccine. It harkens back to a time, a different era, when everybody pulled together and it was everybodys vaccine. We are going to have vaccines, they are going to work, we are going to stop this covid. Ruth. Yeah, so i would say the willingness of everyone to roll up their sleeves. I mean that figuratively with respect to vaccine develop developers, the government, clinical investigators, to get trials up and going and of course participants who are willing to come and do this and really everybody committed to the greater good. I also have to say, as a pediatrician at the school of respectealth, the new for Public Health that has not been present people appreciate the importance and i hope that will continue Going Forward. Absolutely. Gary, you get the last word. This is echoing what everybody else said, but the ability, particularly in the private sector, to respect the Public Interest and collaborate and coordinate in ways we have not seen before, from the gsk and santa fe collaboration sanofi collaboration,s cut against private interest in the name of Public Health. I think that is a positive outcome to what we have been seeing in the last six months. Gary. Me is that there is an end in sight. I think it is months away, not decades away. Months and probably a year or so. It will be a little bit longer before we get back to normal, but there is an end. The way we are going to get there is through science. We are going to see the contribution from diagnostics, therapies, and vaccines. We will get there. I think we need to put together, with all have to support one another, in the final thing i would say is that we should also be very appreciative of our doctors on the front lines and our health professionals. They have been through an amazing experience. We only hear a fraction of the stories, but the people on the ground, when it is all over, we owe them a lot. I think part of what we owe them too is to build systems in the future that prevent this from ever happening again. Well, what a fantastic way to end. Thank you so much. This was a tremendous conversation. You know, incredibly thoughtful, very needed to provide clarity to all of us who are watching this closely, but families who are looking for a ray of hope. Thank you for all of your efforts and lending your expertise today. I will give it back to donna. Wonderful. Let me add my thanks for what an amazing discussion. It truly was outstanding. Thank you very much. Announcer dr. Anthony fauci says it is unlikely, in his opinion, there will be a vaccine by election day. But he remains optimistic about one being ready by the end of the year. He spoke with pbs newshour anchor Judy Woodruff about public trust in a vaccine, how it would be distributed, and other issues related to the pandemic. Thank you for having me in dr. Fauci, you are there so im going to plunge right in. I do not see you on the screen, but i know you are there. I am here, judy. Good to be with you. You are there. Good. Let us start with the basics. Where are we right now, as a country, in the battle against covid19 . If you were asked for a status report, what would you say . I would say it is a mixed bag, judy. You can look at the numbers. They are very serious and very concerning. You know, we have had over 185,000

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