Which a therapeutic is not exist does not exist. In most cases, the need for learning is quite acute. How many be accommodated when be how can the need accommodated when the humanitarian need is so great . That point, the leaders of the team finished the report ofently of a on the topic implemented crisis during the epidemic. I will turn over the podium to the cochair team, who is dr. Jerry kirsch, currently professor at boston university, and he is also managing a very important and exciting institution that has been created there where one can do research on emerging and dangerous diseases. This institutional desperately need any United States, and he is working hard. He and his copresenter, david peters, will be talking for about 15 minutes each, and then we will welcome dr. Carrie hesher from a humanitarian group who did more to save ebola lives than any other single group during the Ebola Outbreaks us then jeremy who is with from the ecb who supported the United States efforts to androl the ebola epidemic at the office of u. S. Foreign Disaster Assistance during that period. Now, i will send over to jerry. Jerry thanks, mead. Thanks to everyone who is participating in those who are watching remotely. We are grateful for your input. A committeenting that was formed at the national medicin to look at clinical result issuesh and there were that were present at the start critically,eak, so particularly for ebola, there is actually very little that is clearly known about how to manage a patient with ebola, to clinically support. There were no therapeutics or that have gone to human Clinical Trials that have shown to be effective and safe to use. That is sort of the genesis of where the committee began. What david and i are hoping to you, to is to hear from get some of your thoughts, particularly around two of the questions. I do not think we need to delve aspects of take study design, but how do you infect integrate research into an epidemic response . Past the time. I think we know clearly that it has to happen terrific question is how. Secondly, how do you create the overall governance and Leadership Structure and what might be the criteria . Tohought it was worthwhile back up just a little bit to some fundamentals. How do you develop new drugs and vaccines . The same thing could be said for diagnostic tests. The issue of human safety is not really as significant as it is to drugs and vaccines. The first thing is the science. You need to figure out what to target for a drug, what to target for enemy and response , a an immune response pathogen. A a lot of it is funded, this upstream research, is funded by public money. The Development Process is something that is done by industry. But you need to determine ultimately whether these things work in humans. Are animals. The food and Drug Administration animalten apply a two rule. Safety and efficacy in two different species. A different drug or vaccine, they differ according to species. And you determine whether it is safe in humans. When you have data from animal studies, you can get Regulatory Approval to start a staterun trial in humans, which is a small study, usually a dosing , listening for safety primarily. Lists of the infection or treatment. Is you can show it is safe in a smaller study, you can move on to a larger study, as well as indications that they perform as you expected, that a vaccine will produce an immune response that you think will be protected. Ultimately, it follows that goes well and something is licensed and is produced, safety trials on a larger scale we really begin to look at the efficacy and more safety data. Most of the candidates that enter into the process fall off for one reason or another before three. To phase one of the questions that might be asked is is the search during ebola different than other things we have done in the past . The first thing is high mortality, no room in treatments, and experimental human infection models are not possible. Leraan do that with cho because we can treat you. Human models have developed vaccines. With an infection like ebola, an used for human trial. Measles, as we know, as a highly safe and highly effective vaccine, cholera, we know how to treat, it is now already achieved an effective vaccine. Ue, but it iseng not difficult to see that trial. They needed a large number of patients all the time, and they need to weigh not a recent sees. Need typically not a recent disease. So why do we need to do research during Ebola Outbreak . Bested to learn how to efforts expectations. I am a physician. I look at what were doing. It is a corn with two sides one site is taking care of people, and the other is learning how to do it better. It is part of the model being in the health care profession. Onassess and investigation and advocacy in efficacy in humans, animals in general do not reliably predicts human response. We have to go to human trials to show that it is working. , youu have good vaccines will actually be able to use them to limit an outbreak. You can use of potentially to prevent a future outbreak. When it fails to prevent an outbreak and you have people who are sick, you need to be able to treat them and treat them effectively. Drugs at a higher standard of care maybe important to survival and reduction and consequences. Of advancing medical knowledge in general and patient care, and for the fda says about Clinical Trials and why they are needed. When we do not know if or how well in your approach will work in people, which are better and n subpopulations in which a treatment may work better, and what is the context . You need that information before you can improve something, a manufacturer can distribute it and use it. Expandapidly possible to. They say Clinical Research is not necessarily for the person who is involved in that clinical trial, but certainly for the future, it is potentially available to individuals who are themselves suffering from a disease, and progress can be made and shown that it can be beneficial. The Clinical Research that was done during the outbreak, we learned very little definitively. Because of the, the National Academies were asked to assess the trial and recommend improvements for emergencies. Health and human services, the assistant and they, the fda National Institute of Infectious Diseases, the academy created 15member committees in the u. S. , europe, and africa. Had three public workshops. Veryd six meetings, comprehensive literature review, Conference Calls for mickey and incredibly accidental Conference Calls, and research. Effective in s not that patient zero rural getting who became ill in january 2013, by the middle of january, the cases aat trial resulting in similar case were recognized as unusual, and the officer out in the goonies in guinea notified the ministry of health, that something unusual was going on. They came to the conclusion that only becausea diarrhea was a part of it, and they had outbreaks of cholera in the past. It was on her mind because the diarrhea was bloody. They did not identify it, it was not until the after part of february that the Ministry Said this may be something different, and they and take ane to come look, and the response was immediate and strong, and they said, this is like a hemorrhagic fever, and the diagnosis was made in the middle of march. The last two months from the point of which an outbreak was identified, and that was really important because at that point already, it has crossed borders into contiguous countries, sierra leone and liberia. And enterprise was built to take care of patients, and they quickly realized that this was out of control. And was different from anything ,heyve ever done with ebola and they kept saying, this is different, this is different. We had dont with smaller, contained outbreaks, the relatively easy to control. Did not recognize, do not agree with them. They declared as a moderate event, which in their languages level 2, which can be supported by the Country Office and regional office. Thephysicians could not get recognition that they need. And it was not until august that the highest level of concern of emergency of International Concern was declared by w. H. O. International response was starting to kick in, and the possibility of doing trials depreciated. Six months had gone by, and there were thousands of infected people, which has never been seen before in an Ebola Outbreaks. Overtimately, there were 28,000 defective come over 11,000 had died. At the beginning, there were no vaccines or treatments, and went inaugust of september 2014, starting to think about Clinical Trials, things started to come out of the woodwork. There was still about 20 potential candidates to be studied. This is a timeline of the outbreak in terms of best cases. The three lines here are the three countries, the three target countries. Here is the middle of march. Ebola is declared. Here is when the International Concern was raised by w. H. O. Outbreak response starts to kick in. It is sluggish, and it is several months later before the outbreak starts to come down. The trials that were done, this is a vaccine trial, you can see they are all initiated when the outbreak is really coming on. You can see there are two cases, and that had major implications for the results. And here are the results. There were five trials. None were conclusive that is worked in what is safe. And was a. Safe. One suggested efficacy, but it will not be enough to convince a Regulatory Agency. And [inaudible] so the initial therapeuticss that for not contributing to mortality. Safe in a context in which a Regulatory Agency would want to see, not at that point. Not from the nature of the data. Trials, oneine effect,e had a possible although it got publicized last december as 100 effective. The problem is that conclusion, is that therview most appropriate Statistical Analysis was not apply. Analysis, ity that was about 65 efficacy, but the at was 0. E around th salt could be incidental but it was effective, but it is toby not effective. So it looks promising. Throughll need to go Clinical Research. Ebola will be the next outbreak. Index outbreak is unlikely to be as big as this one, which means we really have to be prepared to move in as quickly as possible. The Clinical Trials that were inflicted in january, you go through september, october when they think about going through something, getting it approved, the logistics, the rapidity with which with this happened is remarkable. The conditions on the ground, i will talk about that, and they were really chaotic. And because of that, if you focus on the people who are sick and dying and their families who , that was sitting in front of you as something that is important, why are we going to get involved in the research, particularly with patience and presented equipment . There were physicians made it difficult to provide care, let alone having investigated there. There was no consensus on the study or how to organize it. There was very little experience with ebola. They had recognized ebola, although it turns out they had evidence that the virus originated in west africa. And advanced unrecognized, and unrecognized is unknown. There was a failure to engage the community in the process. Some of these experimental therapies were used in asian that were evacuated from west africa. They seemed to do pretty well. Mortality with very low. Suddenly there was a magic medicine, magic syrup that was being given to the foreigners but not the africans. Trust anda lack of their history of civil conflict. And then the Research Group done toes were poorly a triage,lves into knowing what to do and how to do it, and i was particularly as the epidemic was being controlleed. So research is necessary, the best way to ensure that this can be done in these kinds of sentences is to think of it as an epidemic response. The we can be organized tour together. The question is how can you do that . The analysis of the report is clear. It is ethical and has proved to be feasible to do randomized trials. What we need to do is prepare the community through engagement. If it is quite useful at all, it has to be scientifically rigorous and design in a way to produce useful information. Is kind of planning and organizing begins before an outbreak occurs that is right now and requires national and International Cooperation across everything. , Community Participation in the process is absolutely essential not only to cure the epidemic but before the next one happens. [inaudible] you cannot do the Research Without it, but also, the community is part of an effort, so excluding the makes there was little capacity to do Clinical Research, but the key part of our message is that we dont want to separate the research establishment. We dont want first World Research agencies going into liberia and building a beautiful study war in a decrepit hospital where the level of Clinical Care is all. Wful. It have to be across the ,pectrum of health, vision response and Clinical Research. These need to be linked together. Investment is needed now to start moving towards these kinds of prepared response and Clinical Research. Processes. To be linked engagement, coordination among development covers that brought agenda is critical. How do you get the optimal leadership to do this . It may be different if you are trying to do Clinical Research than it is if you are trying to do a clinical intervention. Setup of my setup of my remark. This broader picture of what was going on, what are the needs, response of Clinical Research and why it is necessary. Hopkins and is at the chair of International Health and has great expertise. He would try to raise some of the questions about how do we go forward and how do we create collaboration and leadership to do it. Me. D thanks for inviting im very happy to be here. I want to follow up on the in termsat gerry made of the governance and leadership aspect of the work. I will start with International Health regulations. The ihr, this is a legacy that we have. The legal iterations go back to the 1950s, something that was inherited. It is really about setting the conditions to have an International Protection in response to epidemic diseases for purposes of Public Health and trade. That they haveis not working very well. The problem is it happens from time to time. What we saw here in the failure ihr ihr is basically not just the inability to have the surveillance and Rapid Response, but really in the whole preparation side of things. Who is tasked with preparing countries. Countries are obligated by legal agreement 196 countries to have the in terms of the governance and leadership capacity. Very few of them are. None of the west african countries are in that position. I think liberia is the first one to even do an assessment to this capacity in 2017 and have a long way to go. This is a problem with capabilities. It does have clear governance structures led by who, but he can call on other experts and organizations using this roster of experts and an Emergency Committee and review committee. Was after the sars epidemic. Hopefully, it will be further revised and anything be an area we need to put a lot of emphasis interns of making it in terms of making it work better. Not because of capacity constraints, but lack of enforcement or public accountability, and in fac capa. T, a mandate there been and governance shropshire to incorporate research. What we are seeing is this growing consensus that it needs to be part of the epidemic response and we need to find ways to Bridge Research and practice into the effort of epidemics. How do we do this Going Forward . This is really what i want to talk about about this work in progress. How do we fill this governance gap in terms of moving forward with leadership and governance around research into epidemics . It is a social construct and it is highlighted in the goals in terms of International Affective institutions. The issue around Health Research and epidemic response is that these are really broad stakeholder networks. They have very different interest capabilities, mandates and asymmetric levels of power. We really need to have a governance model that actually recognizes and addresses these concerns. We need to learn that. One thing that the report did was highlight the broad stakwasa knot of stakeholders. Amount of stakeholders. The Regulatory AgencyResearch HealthHealth Agencies are critical and often not talking to each other. They may have different design as things move forward as terms of clinical design. Who as a major role, unicef is involved, humanitarian agencies have played a critical role. Over 70 different humanitarian ngos were involved in the outbreak. Other groups re