Things brought beauty for coming to the center for Global Development today for this interesting discussion. I think that sound effect was appropriate. For the tension that might exist between the need to deliver humanitarian care when there is an outbreak as serious as the recent Ebola Outbreak in the need to actually learn, learn what works to address that and where the outbreak is of a disease which is emerging that is therapeutic, does not exist and even the vaccine does not exist. In those cases, the need for learning and how can that need for learning be accommodated when the humanitarian need is so great. Our speakers today who will be addressing not point are the leaders of the team at the National Cabinet of science to produce a report recently published on the topic of implementing epidemics. Im going to turn over the podium now to the cochair of that team who is dr. Jerry keusch at Austin University and hes also managing very important and exciting institution recently created bear where one could do research on dangerous diseases. This is an institution which we desperately need in the United States and is working hard to bring that to fruition. He and his copresenter david peters will be talking for 15 minutes each and we will have a Panel Discussion which we are going to welcome dr. Terry teicher from the humanitarian group that actually did most of did more in sync more ebola lies than any other group during the Ebola Outbreak and also chairman konydyk who is here with that at cgd and supported the United States after to control the ebola epidemic from his position as director of emergency, what is it, the office of u. S. Disaster assistance during that period. So now ill turn it over to jerry. Thinks, may. My thanks as well to everybody for participating and for those of you who are watching remotely. We are really grateful for your input. I am representing, with david as well, representing a committee that was formed at the National Academy of medicine to look at the issue of Clinical Research when there is an epidemic and there is a multiplicity of issues where president s at the start of the outbreak and critically, particularly for ebola was actually very little that was clearly known about how we manage a patient with ebola, just plain clinical support. Therapeutics or vaccines that it gone through human Clinical Trials and shown to be both effective and safe to use. That is sort of the genesys avoid this committee began. Ill tell you a little bit about that. What david and i are hoping to do today is to hear from you, get some of your thoughts, particularly around two of the questions. I dont think we need to delve into the technical aspects of statistics and study design, but how do you in fact integrate research into an epidemic response . We are past the time when we say that its the happening. We need to now know that has to happen. And secondly, how do you create the overall governance and Leadership Structure that can address this kind of an issue and what might be the criteria . So, i thought it was worthwhile to back up just a little bit to some fundamentals of how do you develop drugs and vaccines . The same thing could be said for diagnostic test except the issue of human safety is not really a significant as it is for drugs and vaccines. First in the Science Community figure out the target for a drug, the target for an Indian Response and what a molecule and pathogen would be useful to die. Same thing would apply to diagnostics. And now you have to fund that r d. A lot of that is funded at this upstream basic research, funded by public money. The Development Process is something that is done by industry, particularly in this country. But you need to determine ultimately whether these things work in humans, we start with animals. The food and Drug Administration has often lied a too animal rule where you need to show both safety and efficacy in two different species and thats in part because response to a single drug or single vaccine may differ according to sbcs new iran. Because it works into animals doesnt mean that works in humans or is actually safe in humans. When you have data from animal studies, you can get Regulatory Approval to start a phase one trial in human, which is a small study, looking for safety primarily. Not people at risk of infection or might need treatment. If you can show that its safe and the smaller study, you can move on to a larger study which looks at both safety and a Larger Population as well as an indication that these performance you expected and that a vaccine will produce an immune response that you think will be good. Ultimately, if all of that goes well and something is licensed and introduced, phase three trials are larger scale and we really begin to look at the efficacy and get much more safety data. Most of the candidates that enter into the process falloff before you get to phase three and even the results of phase three. So one of the questions that might be asked is why his research during ebola different than other things that were done in the past . The first thing is that higher mortality, no proven treatment and experimental human infection models are not possible. You can do that with colorado because we can treat you if you develop the disease and that has been done to develop vaccines. This kind of an infection like ebola, and outbreak is the only opportunity for a human trial. It now has a highly safety and highly affect the vaccine. How do we know how to treat antibiotics in the clinical course and is now already achieved in effect or vaccines . It is not difficult to conduct trials. There are large numbers of trials all the time and dengue is not typically a lethal disease. Ebola and diseases like it stand out is different. Why do you need to do research during an Ebola Outbreak . The first of Clinical Data to learn how to best care for infected patients. Im a physician. I look at what we do is appoint with two sides. One side is taking care of people. The other side is learning how to do a better than those to me are inseparable. Constant learning is part of the model of being in the health care profession. So to assess an investigational drug vaccine for safety and efficacy in humans because animal models in general do not reliably predict the human response so you actually have to go to the human trials to show that it works and its safe. Youd actually be able to use a Public Health approach and use it potentially to predict a future outbreak and when it fails to prevent an outbreak in europe people who are sick, you need to treat them affect early in the addition of drugs to the higher standard of Clinical Care may be a significant improvement in survival and reduction. So this part of advancing medical knowledge in general and patient care and this is that the fda says about clinical trial. We dont know if or how no anguish of them are better than one or another of the treatment will work and what is the context . What is the setting . You need the information before you can improve the mice in something and manufacture it and distribute and use it. And to rapidly as possible expand access to promising new approaches. They say Clinical Research is not necessarily the person who is involved in a clinical trial. Certainly to the future it is potentially available to individuals who are themselves suffering from the disease at the progress can be made and shown to be beneficial. So, to set up the Clinical Research that was done during the outbreak, we learned very little definitively. And because of that, the National Academy is to assess the trials and recommend improvements for future emergencies. Sponsors are three parts of the department of health and Human Services and the fda and the National Institute of allergy and infectious diseases, the academy created a 16 Member Committee from europe, africa. We had three public workshops. We had six Close Committee meetings, very comprehensive literature review, conference calls, email exchanges and incredibly expensive external and internal review process before the report was issued. Basically the context of the outbreak was actually patient zero was the two year old in getting ill towards the end of december 2013. In the middle of january, the trail of cases from that child who relatives and some of the Health Care Providers resulting in similar kinds of debts was recognized as unusual. This was the quaestor of unusual sound mean. The medical officer robin the boonies and getting notified and notice something is going on. They came to the conclusion that outbreaks in the past. They should not have been on their mind because thats not what happens in colorado. So they did not identify it. It wasnt until the latter part of february that the Ministry Said this is behaving differently. Were a little bit worried this may be Something Different and they asked doing work in the country to come and take a look at the response was immediate and strong and they said this looks like a hemorrhagic fever. They took samples come assented to france in the diagnosis was made in the middle of march. The last two months from the point at which an outbreak was identified and that was really important because at that point already did it cross the borders into the two contiguous countries, sierra leone and liberia. In effect, cayman and enterprise to take care of patients. And they quickly recognized this is out of control. This is different from anything theyve ever done with ebola and kept saying this is different, this is different. At least influenced by past experience with ebola, which is smaller and outbreaks that are relatively easily controlled did not recognize and did not agree with. They declared this as a moderate event which in their language is level, which can be supported at the Country Office and Regional Office provision. It didnt get the big Global Recognition that it needs and it wasnt until august the highest level of there and come in the Public Health was declared by who. Now the International Response started to kick in. Only then was the possibility of doing Clinical Trials appreciated. Six months have gone by america thousands of good people, which has never been seen before in an Ebola Outbreak. So ultimately, there were for 28,000 in fact did, over 11,000 who died here at the beginning there were no approved vaccines or treatments and when in august and september of 2014 when you start taking about Clinical Trials, they started coming out of the woodwork. When you eliminated the crazy things, there is still about 20 potential candidates that couldve been studied. This is a timeline of the outbreak in terms of cases. And so, the three lions here are the three countries, the three target countries. So here is the middle of march. Ebola is declared. Here is an International Concern was raised by who. Now the outbreak and response starts to kick in. It is sluggish and several months later before the out break starts to come down. Trials were done, the therapeutic trials, vaccine trials ill initiated in the out ricks really coming under control. There were a few case and not had major implications for the result that regained. Here are the results. Five therapeutic trials. None were conclusive that this works and is safe. One of those trials suggest efficacy, but not going to be sufficient for inducing a Regulatory Agency that is just okay. [inaudible] the original indication was that the therapeutics for not contributing to mortality, but safe in the context of Regulatory Agency wouldnt want to see at that point. No evidence. Thats the nature of the data. One had a probable effect, although it got publicized last december as 100 effect disappeared the problem with that conclusion from our point of view is the most appropriate Statistical Analysis was not applied. When you apply that analysis, so effect of the estimate about 65 efficacy, but the confidence around that estimate spans zero. So it could be coincidental and still could be not affect it. It looks promising. We may have one promising intervention vaccine. They still need to go through unnecessary Clinical Research, which ebola is really going to be the next outbreak. The next outbreak is unlikely to be as big as this one, which means that we really have to be prepared to move in as quickly as possible. So the Clinical Trials that were implemented here, sort of in january they go from september, october when they started to think about doing things in, getting it up route, logistics, the rapidity with which this happened was remarkable, unprecedented and not fast enough. That is the key lesson that its got to be more exact date and efficient. The conditions on the ground and kerry may talk about a couple were really chaotic. Because of that, focused on the people who are sick and dying for their families who are at risk. That was sitting right in front of you as something important. Why are we going to get involved in trying to do research, particularly when you have to deal with patients and protect equipment. Their ambient conditions that made it very difficult let alone having investigators they are in the data. A whole set of issues. There is no consensus on what to study or how to organize it. It was a very limited experience with ebola. They didnt have recognized ebola, although it turns out from epidemiological evidence that it was and north africa. It may have been it. Im recognized and unrecognized is unknown. There were big mistakes in how the messaging was. Data failure to engage the community in the process. Some of these experimental therapies were used in expatriate who are evacuated from west africa, what contract that ebola taking care of patients. They seem to do pretty well. Mortality was very low and suddenly there was this magic medicine, a magic sarah given to the foreigners, but not to the africans, which fed into all of the conspiracy theories and west africa lack of trust and their history of civil complex. And the Research Groups themselves were fully coordinated and competitive to get their products into a trial into triage of which are the most important things to do and how to do it and that was particularly true as the epidemic was being controlled. Some key messages from the report. Research is necessary in the best way to ensure it can be done under these kinds of circumstances is to integrate it into academic response. We think these can be organized to work together. The question is how do you do that . That is the challenge. Questions are raised about the ethics of doing randomized trials. The analysis of the report is clear. It is supposed ethical and proves to be feasible to randomized trial. What you needed to do was prepare the Community Engagement to be able to participate in research is going to be useful at all it has to be scientifically rigorous and designed in a way that would produce useful information. This kind of cleaning and organizing begins before an outbreak occurs. Both international and the National Coordination and across everything local Community Participation in the process is absolutely essential not only during the epidemic but before the next one happens. You cant do the research about it, but it also the community as a part of the effort, so excluding them makes to delete a separate increase adverse conditions trying to do it. The various capacity to do Clinical Research, but the key message to the key part of our message was pseudowant to separate the Research Establishment and agency going into liberia and building a beautiful award in a decrepit hospital where the level of Clinical Care is awful. It has to be across the spec to a Public Health and respond in the Clinical Research. These need to be linked together. Investment is needed now to start moving towards this kind of prepared processes and engage in coordination among the research and Development Agencies to cover the whole broad agenda is critical and how do you get the optimal leadership to do this . It may be different with Clinical Research then if youre trying to do a rapid clinical intervention. So that is the setup of my remarks for this broader picture of what was going on, what it means and why its necessary. Now if not quite apparent. David is that hopkins and is the chair of the department of International Health really has great expertise on these issues. Hes going to raise some of the questions about how we go forward, how we create the collab