Ready or Not: Medical Countermeasures for Pandemics

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Public Health Threats and Pandemics

Steve Davis, president and CEO of PATH, and Richard Hatchett, acting director of the Biomedical Advanced Research and Development Authority (BARDA) discuss spurring the development and delivery of medical tools to prepare for emerging infectious disease outbreaks as part of the Global Health, Economics, and Development Roundtable Series.

THOMAS BOLLYKY: All right. Well, thank you so much for coming on a truly horrible Washington morning. You are the brave, the waterlogged, the devoted to medical countermeasures. So I’m grateful that you have turned out for this event.

This is probably not news for most of you in the audience, but growing populations, warmer temperatures, urbanization, easier trade and travel are changing the world in ways that is conductive to the spread of emerging infectious disease. The recent Ebola and Zika outbreaks have dominated news headlines and have had a terrible cost to life and livelihood. But a more lethal disease would do far worse. Diagnostics and vaccines aren’t the only answer to this emerging threat of infectious disease but they do help control epidemics early and sustain the engagement of medical personnel and volunteers. Yet, serious questions exist—or, continue to persist on how cost effective delivery and development of medical countermeasures can occur, particularly amid an ongoing outbreak.

This is really because of two factors. First, we have never developed a vaccine in time to change the course of an outbreak. So that’s not heartening. And, in the recent two outbreaks that we have had, the performance in developing medical countermeasures to address those has not been particularly encouraging. It’s been nearly two years, or more than two years rather, since the Ebola outbreak began in West Africa. Hundreds of millions of dollars were invested in clinical trials for more than a dozen drug and vaccine candidates, but no vaccine or drug for Ebola has been submitted for regulatory approval. The most optimistic scenario for the availability of a Zika vaccine is mid-2017, at the earliest, but, seeing more recent investments in Zika countermeasures and the timeline that they have, it seems like it’s likely to be significantly longer.

The second reason is that we are in an uncertain funding environment. The National Academy of Medicine estimated that the annual cost of pandemic preparedness would be between $3 and $5 billion, which is actually a good investment when one considers the potential cost of uncontrolled epidemics, but it is well-beyond the current prospects of U.S. funding, let alone globally. Some of you may have seen late yesterday that the U.S. Senate authorized a $1.1 billion Zika bill, which included $397 million for R&D, split between BARDA NIAID. But the overall apathetic funding response to the Zika outbreak—not just in the U.S., but really globally—raises concerns about the ability to raise funds to combat emerging global health crises, particularly done ex ante and in the abstract.

We are really fortunate today to have the two right speakers here to guide us through this discussion of how to spur cost-effective development and delivery of medical tools for emerging infectious disease outbreaks. On my left, I have Rich Hatchett, who is the acting director of the Biomedical Advanced Research and Development Authority, BARDA, and is also an acting deputy assistant at the U.S. Department of Health and Human Services. For those of you who do not know, BARDA develops and provides medical countermeasures to manmade and natural threats, which includes pandemic influenza and emerging infectious diseases. Rich is a physician by training. He’s an oncologist, if I read his biography right. And, he was formerly chief medical officer at BARDA and on the National Security Council staff.

To my right we have Steve Davis who’s the CEO and president of PATH, which is an international nonprofit organization with a long history—almost 40 years long—of developing innovative appropriate technologies to address the poor’s health needs around the world. Steve previously led the social innovation practice at McKinsey, still teaches courses on that subject at Stanford’s business school, is a member of the Council, and was one of the greatest contributors to our recent taskforce of NCDs. So I’m pleased to have him here.

Each of these speakers will speak for 10 minutes. Rich will go first. Steve will go next. After which, I will ask them a few questions, and then you will have the opportunity to do the same. When you want to be called on, just flip your placard up and I will call in you the order that I see you. The meeting will end promptly at 9:00. Today’s meeting is for attribution, which means anything you say or ask may be read back to you at your confirmation hearing. (Laughter.) It also means that participants are welcome to use and cite the information received at the meeting and attribute it—that information to whomever speaks at the meeting.

If you haven’t already, please turn off your phone or your BlackBerrys. I won’t lie to you and say it interferes with the sound system, but it’s awfully rude when they do go off when people are speaking. So I’d be grateful if you turned it off. And with that, let me turn it over to Rich.

RICHARD HATCHETT: OK. Thanks, Tom. I am going to take issue with your characterization of this as a lousy day. For those of us inside government it’s a great day. We have a budget. (Laughter.) I don’t have to go in and start activating my shutdown procedures, which is what I was planning to do absent a budget this morning. It’s also a good day—I’m not going to say a great day—but a good day in terms of the Zika funding. We have been waiting for seven months—more than seven months since submitting a request for Zika appropriation. The bill that we got is a good bill. It’s not the bill that we asked for, but it provides ample resources that will allow us to continue our struggles to develop medical countermeasures and to provide a public health response to Zika.

I will say, I think we have one more action pending this fiscal year, but within a few hours I would have been down to about $300,000 out of $132.4 million that I had been provided by the department prior to the appropriation. So I would say that the bill came just in time. That said, you know, it’s not at all surprising to me that we have had delays on the supplemental. That is, actually, the history of responding to emerging infectious diseases reactively. I was thinking on the drive down this morning, it’s a bit like waiting until your country is invaded, and then starting to design the weapon system that you need—and probably with about the same results. You either don’t get the weapon you need in time, or you perhaps build a faulty weapon system that could potentially blow up in your hands.

Prior epidemics—I’m going all the way back to the swine flu epidemic. For those of you who are old enough to remember the swine flu epidemic in 1976, there were tremendous delays in appropriations after President Ford announced that there was going to be vaccination program. And it was all about liability and indemnification of the vaccine manufacturers in that case. It took the Legionella outbreak, which nobody knew was Legionella at the time, to scare Congress into acting in the summer to provide the necessary funds. We had reasonably quick appropriations for pandemic influenza in 2009 and for Ebola a couple of years ago. But it doesn’t make any sense to think about responding to disease reactively.

I’d like to differentiate the response to Ebola from the response to Zika. Ebola has been a part of our—a part of our mission space for—because if concerns that it could be used by terrorists. And so we had actually 10 or 15 years of prior investment, probably not at the level required, but 10 or 15 years of prior investment in developing vaccines and therapeutics. And so when the Ebola epidemic spun out of control in West Africa and it became clear that a medical countermeasures response was going to be part of the overall response, we had something to build on. And although we don’t have any licensed vaccines or therapeutics, we were able to move vaccines and therapeutics into clinical trials, in a very austere and challenging environment, relatively rapidly—certainly within six or eight months of deciding to do so. And that was in a very austere and challenging environment, where we had to actually build infrastructure, build a clinical trials capability.

And that was due directly to the fact that we had all of that prior investment. With Zika, we’re starting—obviously Zika was not a threat that was really on anybody’s radar screen. We are starting essentially from scratch. And the timelines that Tom mentioned, I think—I would have said 2018 would be the earliest optimistic, you know, time for availability of a vaccine. And it could be considerably longer. Drug development programs are fraught with problems. You just have to deal with the challenges as they come along. There are often delays. And so if—I think we will be lucky if we have a vaccine in 2018. But that’s our current aspiration.

I want to talk just very briefly a little bit about BARDA. I’m assuming that many of you are not familiar with us. We were described on “60 Minutes” once as the organization within government that nobody knows about. BARDA’s a relatively new organization. It was established in 2006 by statute by the Pandemic and All Hazards Preparedness Act. Our statutory mission is to develop medical countermeasures against threats to U.S. national security, and I will underscore U.S. because of the nature of today’s conversation, including things that terrorists can use—chemical, biological, radiological, and nuclear weapons—pandemic influenza, and emerging infectious diseases, which has never been defined very precisely what that means and leaves a lot to the imagination and has not, until even as of today, not prompted Congress to give us an appropriation to have an emerging infectious disease program. So we have a CMRM program. We have a pandemic influenza program. And we have begun to respond to emerging infectious disease threats when appropriations are made available to us through supplemental appropriations or reprogramming, as was the case currently.

BARDA’s mission really is a preparedness mission. We are actually not configured to be a response organization. But over the last four years, we have been essentially in continual response mode. And we recognize it as a strategic challenge for the organization to reconfigure ourselves to be able to respond. And I have set as one of our internal goals—we have toggled back and forth over the last four years between various kinds of emerging threats. Half of them have been influenza threats—H7N9, H3N2V—and the others have been more classical emerging diseases or emerging diseases other than influenza, which is the perennially emerging disease—MERS, Ebola, now Zika. My internal goal is that we, you know, would not have to depend on good luck to be able to toggle back and forth one disease at a time, but essentially to be able to fight wars on two fronts. If we had to fight both an influenza threat and an emerging disease threat in real time, I think it would break the organization, the way we are currently configured. And so that’s a very important goal for us.

The way we have succeeded is by providing—I don’t think it would be inaccurate to think about us as the product development partnership within government. We provide funding for research and development. We provide a whole series of product development services—and I won’t go into that at any length right now—as well as access to core subject matter expertise. We have a very talented staff of about 160 people who have expertise in manufacturing, engineering, regulatory and quality affairs, clinical trials. We can bring all of that to bear in our partnerships. The third important element for our sort of recipe for success is that in the CBRN domain and in the pandemic influenza domain, we have also provided pull incentives, procurements of products for stockpiles. And that’s been a critical component of how we succeed.

Overall, we have achieved a great deal of success. I think we have 23 products that we’ve supported that have reached FDA licensure approval and clearance. We’ve had five important approvals from FDA, just in the last year. That’s pretty good, even by industrial standards. For Zika, we have supported—we are now supporting the development of five vaccines, four diagnostics, two blood-screening assays and two pathogen reduction technologies to protect the blood supply. But we fail. And we fail a lot. And we—it’s part of how we do business is being tolerant of failure. You have to have thick skin to operate in pharmaceutical development. And you have to be ready to fail and you have to be ready to make choices about killing the programs that are failing.

So in order to succeed, we take lots of shots on gold. It takes lots of resources to do that. And it takes continued, sustained support because, like weapons systems, our development efforts, you know, can be thought of almost in decadal terms, sometimes. Some of the products that we’ve been working on, you know, we have been trying to develop for 10 or more years. And that in the context of an emergency response, you have to bear that in mind. I think the people that think that we’re going to have emergency response systems that can deliver de novo countermeasures in real time in a timeframe that is relevant to emergency response to emerging diseases, you know, either or delusional or are looking over the horizon.

And so key to being prepared to responding to threats like Zika and like Ebola is being willing to recognize that emerging infectious disease happen, and to make investments in advance, and to support programs in advance so that we can key up countermeasures, or even broad-spectrum antivirals, or novel platforms for developing countermeasures that we can turn to when we need them. And that’s going to take sustained support. Given that we’re in Washington, that means through the annual budget cycle, as long as government’s going to be involved. And without that support, we’re going to be in a situation like we’re in right now with Zika, which is, you know, trying to respond reactively and trying to catch up with a disease that moves rapidly, doesn’t respect borders, and isn’t waiting for us to develop our countermeasures.

BOLLYKY: Great. Thank you.

STEVE DAVIS: Good morning. And thanks, Tom, for organizing this. And delighted to be here in rainy Washington—the other rainy Washington; it’s actually sunny where—the other Washington—and join you. I won’t talk about the why. I think we know the what and the why. We have evidence that these epidemics and pandemic models are going to continue maybe at a pace faster than we’ve ever seen. And we sort of recognize we have to do something differently than the way we’ve done in the past. And so I’d love to talk a little bit about what that might look like and then talk a little bit about what PATH is doing, and some ideas.

I was caught on tape actually at Davos this last year, sort of mixing my sports metaphors which is—I’m inclined to do, and kind of getting in trouble by our PR people because at one place I said that, you know, these pandemic responses is like literally six-year-old soccer games, right? It’s, you know, there’s a ball and everybody’s flooding over there. And it certainly would be true during Ebola, having gone up to the Hill a few times, that that was certainly the case up there where, you know, everything else like, you know, malaria and HIV went out the window and everybody—the only thing that mattered was Ebola at that moment. And that’s a risk to the global system, that if we don’t—if we continue—we shouldn’t be six-year-olds playing soccer.

And then my other metaphor was rugby, which I’ve never played, but on the R&D side particularly, these outbreaks have looked like a massive rugby scrum, that something happens, everybody jumps in, nobody knows who has the ball, nobody knows which candidate. And slowly, you know, it starts peeling away and you start seeing, OK, who’s actually—what candidate is moving forward, what issue—what’s the analysis of prioritization, et cetera. And we can do better than that.

So moving away from sports metaphors, I think the agenda we are all engaged in, and deeply at times, is how we as a global community—both a global health community, but also a national and a global security community—think about doing better in creating mechanisms and systems and, I mean, starts with the conversations, but it has to end with the deliverables on doing better. So when we think about this, and I’ve been quite involved in many aspects of this, but it’s sort of a—kind of a continuum.

And I think one of the challenges we’ve had in the conversation and in the literature is we kind of still do the classic these are in these stovepipe silos, where there’s the large conversation—let me kind of describe the continuum. I think there is the in-country or global preparation—preparedness issue at work. And this is, you know, the work we’re doing increasingly, some of the money that was appropriated last night will go into this, which is about surveillance, setting up, you know, emergency response systems, understanding better what kinds of laboratory capacity we have in a variety of different parts of the world, supporting governments and countries and others to get that in place, and having some sort of mechanism so that even if you have an EOC it’s talking to an EOC across a border somewhere.

And that’s a big lift. And it’s a very, very, very scattered landscape today. CDC’s obviously taken a lead now with global health security work in that area. And I can talk more—PATH is actually one of their key partners in that work. But that’s a lot of work and a lot of commitment. And I think—and we’ve got to sort of pursue that piece of the agenda. But in the middle, of course, the place that gets most of the attention is just the response mechanisms themselves, the pure humanitarian response, outbreaks occurred, who’s in, who’s coordinating, how fast, what’s the appropriate certainly downstream response, but also how does that translate back to what do we need to do from a tools and devices and vaccines and drugs point of view.

 

And as most of you know, post-Ebola particularly, but this was kind of—but if you actually go through the history of this, post-SARS, post-H1N1—there’s multiple recommendations and reports and panels that have been convened about what, you know, can be done differently, what WHO’s response should or shouldn’t have been, et cetera. But that’s a critical piece of all of that as well.

And then, of course, there’s the part that I think that Rich and I are spending a lot of our time on as well, which is what do we do on the more upstream side of this? And this is both a preparedness and a response, but how do we actually deploy the right kind of capital, science, capability, mechanisms to make sure we have—and we kind of talk about it in our shop at least—about the just-in-case—the preparedness side—which is the just-in-case tools. And, you know, just in case we need it, we need a stockpile for X vaccine. And figuring out what that looks like, how many, how much, how to make those choices. And then, of course, there’s the just in time. Just in time is we needed a Zika diagnostic yesterday, but now that it’s—you know, it’s come about, we need to move as fast as we can and have a system that can get that moved fast. And that’s a regulatory process and a coordination and a capital allocation process. So those are the—sort of the continuum that we’re working on across that.

PATH, and maybe I should step back just a little bit, the perspective PATH particularly brings to this, as mentioned, been around 40 years, has been a leader in the global health innovation space. And we kind of have five core areas of innovation. We work extensively on vaccines—everything from new vaccines to vaccine introduction and vaccine tools. A lot of work on drugs and drugs access. The third area of significant work is diagnostics, increasingly understanding that the de-linkage between health systems and tools is often we just don’t know what we’re treating or need to treat. And there’s a lot of opportunity in that space right now.

And then the fourth is a lot of work on devices and tools. So this—and there are a number of devices and tools that are really relevant to this issue from, you know, chlorinators to get the water clean to easier injectable—injection techniques, and a number of things like that. And then the final piece is a lot of work, and probably our predominate work, is on system innovation. So how do you actually think about changing systems, processes. Digital tools are enabling a lot of that. That’s actually our biggest portfolio of work. And we do that always just very much in concert with countries.

So across the range of work, which has been focused on both the traditional—I would say—that’s kind of a funny way to say it—but the traditional infectious diseases and NTDs and now a lot of NCDs. We’ve never actually really focused on pandemic preparedness as much as we could have. And partly it was—sort of our focus was on the things that are killing the most people in the world, honestly. And but we were consistently being, then, pulled in. You know, all at once, you know, how do we—you know, we need to second our vaccine specialist because we do more clinical trials in Africa and South Asia than anyone else, in really low-resource settings. We do a hundred a year. So there’s an expertise that is being asked to be—OK, now we have to figure out how to do this very quickly.

And so as we started getting pulled in, we recognized that we needed to be much more thoughtful about how we actually go about, do our work in this important area. So that’s involved us now into focusing in a couple of different categories, which I’ll mention and then get to some recommendation. One is in very active, as I mentioned, in the global health security agenda. So we’ve actually been—during Ebola, helped flip the malaria work we were doing in Senegal to standup the EOC there, which ended up being very successful. And that’s actually one of the learnings, I think, that—how do we redeploy groups of folks working in certain categories toward, you know, when outbreaks occur?

But the GHS, the Global Health Security agenda, is quite broad. I think it’s still in very much a learning phase, but we are now in the DRC setting up, you know, an EOC there in Vietnam, a lot of work on surveillance in Tanzania and other places around the world, working with government and with the CDC and with others, figuring out where that sort of mechanism of surveillance data and communications all has to occur in these areas. Kind of in the middle is we’ve actually continued to work on a number of interesting tools and devices and increasingly vaccines and diagnostics that are more relevant to this category. And I can go through, but we are being asked to look at, you know, the diagnostic environment, and particularly with the ability to do clinical trials in some of these low-resource settings.

And then a final thing is—which we haven’t talked about and I’ll wrap on this—is that we’ve been very engaged in this work on what’s now called SEPI (ph). And if—those of you—a lot of heads are nodding, so I won’t go through the whole history, but a group of us met in Davos last year, which was really to address the upstream side of this conversation with industry and with government and a number of players, co-hosted by the Welcome Trust, the Bill and Melinda Gates Foundation, the World Economic Forum, and the Norwegian government. And that’s ended up to a new entity that’s been created, the secretariat sits in Norway today with the Norwegian government for an interim secretariat, to actually go raise money to create a global mechanism for identifying certain pathogens that will then be targets for creation of new vaccines and to stockpile those vaccines. A lot of work in progress, but it’s actually a very encouraging sign.

So I actually think—you know, there’s a lot of cynicism in this space. Honestly that, oh, here we go again, and this is a—you know, we are just part of the soccer game, right? That’s we’re just chasing a new ball, and we’re all here today, but tomorrow it will be something else. But I actually think we have seen a really important switch to where there is really some political commitment around this now. Unlike the—maybe the last three or four times where those reports sat on a shelf, there’s a lot of attention to actually we’ve got to do something about this now. And we’ve—you know, we’ve learned, we’ve seen it, we know what’s coming. And I think that’s the good news.

I think when we go forward we need—there’s sort of four quick things. One is really do need to learn and act on what we learned in the past. I mean, there’s a lot of history here. And sometimes we get in these conversation and you feel like this is a novo problem. You know, even, you know, the misperception that Ebola was a pathogen that emerged last year. It’s like, yeah, it’s been around, what, 40 years? So, you know, we got to learn how to—and then we got to look at both long and short-term responses to that, because one of the things we’ve seen is a lot of short term reaction. But a lot of the work we need to do in this area is long term.

The second is we’ve got to—this is a multisector response. There is no way we can do this without civil society, industry, and government working together. And one of the challenges has been those have been three separate strains of activity in many instances. And so one of the biggest challenges here is how to create mechanisms. SEPI (ph) is one effort, but to really try to figure out how to do that smarter, and particularly with a great geographical dimension. So this isn’t a bunch of folks sitting here doing that; it’s a bunch of folks working all around the world.

The third is, you know, we know that we can do brilliant work, Rich can do brilliant work, our scientists can. But if we don’t have a health system to introduce this work in, we’re not going to be able to introduce it—I mean, succeed. So, you know, we can’t keep our eye off that ball, even though I recognize some folks, like Congress, didn’t think that was too important last night. But nonetheless, we’ve got to keep working on it.

And then the final thing, which I continue to say in this area, is we’ve also got to remember that, you know, far, far, far more people—we don’t actually have—there’s some work on whether—can we measure it. In West Africa in the last 24 months, during the Ebola cycle, died because they weren’t able to get the malaria drugs that they would have been able to get otherwise than people who died of Ebola. And not to diminish the risk of something like Ebola, but we got to understand that, you know, we have far more people in the world getting sick and dying of all these other diseases.

And so one of the issues that we want to keep pushing on the table is are there opportunities when we do this kind of work that Rich and I are talking about, that we can find dual purpose approaches so we can actually—as we’re learning about Zika, we can learn about malaria and dengue and other sort of ongoing things as well. And how do we make sure we tie those together and not see them as a completely separate effort.

BOLLYKY: Great. Great set of remarks for both of you. Let me ask a couple of questions.

The first is you mentioned, we had a head start on Ebola. It was something we had worked on. We had candidates. If you hear Tony Fauci talk about the ways that the development of countermeasures for pandemics will be addressed in the future, it’s really with vaccine platform technologies. Those platforms will be pretty far advanced, and you can adapt different classes of platform technologies to address different diseases. But he says even under that scenario, you’re are shaving six months off of the process, two years off of the process, not completely changing the overall trajectory or timeframe for the process. So even with a head start, even with these platform technologies, we’re still talking about a pretty long lead time. And as you mentioned, whether it’s a six-year-old soccer games or many shots on goal or—I don’t know what other sports analogy we could come up here—this is a lot of resources for not a ton of timely success.

Is this really—

HATCHETT: Not synchronized swimming. (Laughter.)

BOLLYKY: Not synchronized swimming, indeed. So the question is, is this really the strategy we should be emphasizing? The current Zika bill that came out had $75 million for U.S. domestic systems, and precisely zero for international health systems or surveillance. Should we have a system that’s really emphasizes health systems, local surveillance, and diagnostics and relatively deprioritizes some of these other investments, especially in an environment of scarce resources? Why should countermeasures be taking the lead on resources?

HATCHETT: So there are actually a bunch of questions embedded in that comment. I mean, a couple of thoughts. So surveillance—in terms of responding—once you get to the point of needing medical countermeasures and vaccines, you’re really in trouble. And unfortunately, that’s where the Ebola epidemic got to, that it seemed like, at least or a time before sort of behavioral responses kicked in, it really seemed plausible that the Ebola epidemic could spread across all of sub-Saharan Africa. It was really frightening. And that motivated, you know, even greater acceleration in terms of medical countermeasure investment.

But clearly, you know, the ideal thing is to have good surveillance systems, particularly in countries where we’re likely to encounter emerging diseases, and to have those surveillance systems trigger emergency responses early so that you don’t get to the point that the only solution appears to be a medical countermeasure solution. And so that’s a critical piece of it. And, you know, that isn’t want BARDA does. But anyone who’s thinking holistically about the public health response to emerging diseases, you know, needs to prioritize and emphasize the importance of early detection and early response.

And so, I mean, the World Bank’s—I’m probably not going to get the title right—the Pandemic Emergency Financing Facility is designed to be exactly that kind of a contingency fund that can move resources early during an outbreak so that—you know, if we had spent $100 million responding to Ebola in early 2014, there would not have been 11,000 people who died, or 28,000 people who became infected. But we didn’t have access to those resources. And there were all kinds of reasons that the world failed to respond appropriately. So let me—let me say that.

And let me go back and address your question about platforms, and the potential value of platforms. I think you have to differentiate a little bit. You have to sort of have an appropriate taxonomy of the problem. And you have to differentiate between epidemic diseases—and most of the threats that we’re talking about are epidemic disease and pandemic diseases. And there are very few legitimate pandemic diseases other than influenza. I mean, I think you could argue that we’re in the midst of a Zika pandemic that appears to be unfolding in time, chikungunya, perhaps, and certainly HIV. I mean, that’s the pandemic of our time, obviously.

But even with the pandemic diseases, the tempos and time frames differ. You know, and so flu is the pandemic disease that can disrupt the continuity of governments and society. These other pandemic diseases might be diseases might be diseases that could spread around the world, but it’s on the timeframe of years or even decades, in the case of HIV. And once you differentiate between epidemic diseases and pandemic diseases, it changes the way you think about a medical countermeasures response.

So an epidemic disease, like Ebola, which has the potential, evidently, to infect even thousands of people in the right socioeconomic milieu, can be addressed by comparatively small stockpiles. I mean, if we had had a stockpile of 10,000 doses of a functional vaccine, and we knew how to use that vaccine, and we had the capability to respond rapidly to an outbreak, we could have completely suppressed the West African epidemic early in the response. And so pandemic diseases, on the other hand, you know, require sort of massive, you know, infrastructure to produce vaccines. And I don’t think you’re ever going to be able to respond to pandemic diseases in real time.

We’ve been thinking a lot about the business model to address emerging infectious disease threats. And there are emerging diseases that we already know about. Ebola would have been on that list. Coronaviruses are certainly on that list. Zika would not have been on that list. But there’s a comparatively short list of diseases with the potential—with epidemic potential for which we have no countermeasures, towards which we could direct advanced research and development programs, and carry products to the point of, you know, completing phase one or phase two clinical trials—which is much less expensive than taking something all the way to licensure—and creating comparatively small stockpiles, if we were willing to make those investments.

That doesn’t address the Zika problem. It doesn’t address responding in real time to a truly novel threat. But it would reduce our risk exposure. And that’s really—in government, when you have scarce resources, that’s what you’re trying to do, is reduce your risk exposure to the point that, you know, to some equilibrium where you can tolerate the remaining risk, and you have some mechanisms, like platform technologies, in place to accelerate to the extent possible the response to a truly novel threat, while reducing your risk exposure to threats you can predict in advance.

BOLLYKY: Great.

DAVIS: And let me just—so I thought of three adverbs to think about that question. One is strategically. I think the trends are right on two fronts. One is—an I’ll just sort of do this with just the Cliff Note version. But it’s moving to where global health is actually a part of a security agenda and discussion is not only the right thing to do, it’s a good idea from sort of the politics of it as well. So I actually think it’s totally authentic and it’s actually, I think, the right thing to do.

I think also the other one is I would say strategically moving away from individual platforms, individual—I mean, individual projects, individual siloed pathogen work, and to say we’re going to create some cross-cutting functional capability to address—you know, that’s what platform technology—I come out of the technology work. I mean, platform technology is building cross-cutting, functional capabilities against certain types of approaches. And that gives us so much more agility, so much more strength to kind of have—to react quickly and to be more sustainable. And I think those two strategic moves are critical and important.

The proportionality—I do think we have to be careful. While I may be very concerned, if you look at the total spend on, you know, HIV—I mean, we just raised $13 billion last week, we being the global community, for HIV, TB, and malaria. So the proportionality, this is—this is—it does seem to catch the headlines. But the trend line is that we’re still sort of investing proportionately. And we’ll hopefully—I mean, there’s a lot of disproportionality if you look at other aspects of global health. But I don’t think this—like, you and I talk all the time about the disproportionality of the NCD budget against everything else. But that’s—this is not a huge aberration in that pattern.

And then prospectively I do think—the point is, yeah, it’s easy to kind of go back in hindsight and say, well, it turns out we spent all this money and we didn’t get—you know, we didn’t get a candidate on Ebola. But prospectively, we were facing what could have been a horrible—I mean, a horrible pandemic. And so, you know, I think we just have to keep—these—the judgement around how we do it. We got to get sort of ahead of that, but it’s always going to be done without any crystal ball. I mean, that’s the nature of this work. We simply—it’s not a shot—I mean, we take shot to goals, but there is no predictability, as there is in sports, as to sort of your offense. We don’t know what the pathogen’s going to be, where the outbreak is going to be, and whether we’re going to be successful with the science.

BOLLYKY: Great. So one more question, but after I ask this I am turning it over to the audience. So think of your questions now and I’ll call on you.

So one of the reasons why I was driven to organize this event is that Steve and I wrote a piece looking at pandemic preparedness and R&D that came out the same week as your Nature piece on the very same topic. And the pieces are awfully, awfully similar. And that reflects either a poverty of new ideas—(laughter)—or a real confluence in thinking between the global health community and U.S. government actors on a lot of these issues. And I’m wondering: what is the right way to coordinate the activities among those two communities?

Now, as an aside, for those of you who haven’t read it, we have Steve and my piece outside. It, like Rich’s article, proposes sustained and consistent money for R&D, international coordination, systems to support both the upstream work and the downstream work of development and delivery, and advocates looking at lesson from past initiatives to guide those efforts. In Steve and my case, we focus on the lessons from the last decade of global health. In your case, you’re focused on the recent lessons from BARDA’s experience. Really, the articles are awfully similar. So is there a way that the initiatives of these two communities can be combined? Perhaps by dividing up the responsibilities, maybe along the lines of that you described of investing in epidemics versus pandemics?

Investments in epidemics strike me as a little less—perhaps from the outside—a little less predictable than what you have described on pandemics. Certainly nobody would have predicted a Zika epidemic. I would argue, in terms of an epidemic, nobody really would have predicted Ebola either. So in terms of Ebola R&D it was really being done from the bioterrorism perspective, not from a widespread fear that an outbreak of this disease would spread on its own through trade, and travel, and migration. So is there a split of responsibilities along the lines of one community focused on epidemic preparedness and the other focused more on pandemic flu preparedness?

HATCHETT: So just with respect to Ebola, I mean, I clearly think I would concur with you that we have become complacent about its epidemic potential. And because we had had 20 or 30 prior outbreaks that had been comparatively easily contained—I think the biggest prior outbreak was probably less than 500 people. And that’s kind of a shame on us for not recognizing that, you know, you put the disease in the right milieu and, you know, with the right set of road networks and environments, where it can get into dense urban populations, and suddenly something that you think you understand well can become something that can spread out of control, particularly in countries where public health systems have been decimated by, you know, years of civil unrest.

I actually—I don’t think there’s as much distance between the things that Steve has been saying—I mean, I’ve been sort of nodding over here and he’s talking about products with, you know, multi-use value, and platforms that can be, you know, turned to address multiple kinds of problems, including our epidemic or pandemic problems, and our—you know, I would say more traditional global health problems. I wouldn’t, in speaking about the distinction between epidemic and pandemic diseases, I think it changes your estimation of the resources required. And you can make a justification—it’s much easier to make justifications in developing the capabilities you need to address epidemic threats—which I would say the majority of the things that we’re talking about really don’t have pandemic potential—and the kinds of investments that you have to make in developing a capability to respond to pandemic threats.

I mean, the U.S. government has spent on the order of $6 (billion) or $7 (billion) or $8 billion over the last decade thinking about pandemic influenza, and that includes creating stockpiles of antivirals, pre-pandemic vaccine stockpiles. It includes supporting manufacturing infrastructure, making of hundreds of millions of dollars, investing in manufacturing infrastructure that can churn out hundreds of millions of doses of vaccine within a few months of a pandemic. And so if you frame things as—I’m not answering your question, but it’s an important point. (Laughter.)

BOLLYKY: Give back the microphone. (Laughter.)

HATCHETT: If you frame the problem as a problem of pandemics, it’s great or scaring people and perhaps for mobilizing resources, but if that’s really what you think the problem is, it entails a whole set of investments that are far above and beyond what we’re talking about in terms of developing vaccines against the infectious diseases that can disrupt societies—you know, that have the potential to disrupt societies. And that’s what we’re trying to prevent, because once you have—it doesn’t—just like with the anthrax attacks of a decade ago—it doesn’t actually take a lot of cases of a disease to be incredibly disruptive.

I mean, SARS if probably the disease in our experience that hundreds of years ago would have been a pandemic, but it would have evolved over a timeframe of years or decades. And it, you know, appeared explosively. There were 8,000 cases, but it caused $40 billion worth of economic damage. And so the investment—you know, and it was put back into the bottle through public health intervention that didn’t require medical countermeasures. But medical countermeasures, if we’d had them, would have been very helpful. And it would have been helpful in stopping the epidemic. And it would have been helpful in preventing that $40 billion worth of economic losses.

And so the argument for—I mean, a crass argument for developing these products, besides the immediate number of lives that can be saved, is the justification for the investment is an economic justification rather than a pandemic threat justification. And I completely avoided your question. I didn’t mean to, but—

BOLLYKY: No, that’s great. It is—that’s a good answer anyways.

DAVIS: Yeah. And really quickly is I think that there’s sort of the ideal and the pragmatic question here. The ideal world is that pandemics, epidemics, and, you know, ongoing infectious disease challenges are—we knit that all together and we, you know, create some sort of global way to get that figured all—it’s nice. We’re doing some great work in that area to try to at least connect the dots, do better knowledge management. So we have to be fairly pragmatic about what we can do when now. It’s been interesting, even in this question about what this SEPI (ph) entity should do, it’s vaccines only. They’ve taken flu off the table for all sorts of complicated reasons. But that’s a very—it was drive by sort of politics of industry engagement and what’s commercial or not.

So, you know, is that an ideal scenario? It’s sort of like, of course not. Is that the way we’re going to be able to move this thing forward? Yes. So I think that’s kind of where we are on this, is we’ve got to just pick a few things and get them right and then go for the next one, and then try to knit this together better.

BOLLYKY: Great. We have lots of questions, and little time. So I’m—some people were smart and started raising their placards early. So I will reward them for their entrepreneurship—(laughter)—and call on them in the order I saw you. I am going to take people in groups of—we only have 10 minutes—so please ask a short question, and in a form that actually sounds like a question. And I will start with Maureen (sp) and then Dara (sp).

Q: Thank you. This is great. I really thought it was interesting. And despite the request for one question I’m going to ask two.

BOLLYKY: No, just one.

Q: Ask—OK. Then I’ll go back to Tom’s question, which is: There’s a tradeoff between doing a lot in terms of preparation and what is it that you prepare for—because there’s a whole range of things that you can prepare for—and your whole delivery mechanism, because Ebola happened because—I mean, and you, Richard, sort of referred to that—but the countries that had systems that worked had much less of a problem than those that didn’t. So, I mean, how do you trade this off because, as Tom said, resources are finite. And we’ve got to figure out how to do this, because you can have all the vaccines you want. If you can’t get them delivered, then you really haven’t solved the problem.

BOLLYKY: Great. Dara (sp).

Q: Hi. So my question is about antimicrobial resistance and addressing multidrug resistance and TB, actually. So I just wanted to know in your opinion what role BARDA plays since, you know, one fourth of the total AMR deaths will be related to TB. And just for quick reference, I actually just converted my TB test. So it’s here. Like, it’s relevant.

HATCHETT: So quick answer. In terms of the tradeoff, I—as I said, medical countermeasures are the response of last resort. And when you’re thinking in an international context, they’re—the delivery problems are so immense that they—I would think that they would tend to predominate in terms of thinking about investments in terms of global health. BARDA’s mission—and I underscored this originally—was to protect U.S. populations. And we’ve only sort of been, you know, pulled into these international responses quite recently. BARDA doesn’t have to make that tradeoff, just because of—we have a sort of defined mission space. That’s a societal and a political challenge.

To quickly address the—BARDA has very recently taken on antimicrobial resistance as a primary problem with the mission space. We’re just getting to the end of our first year of funding for the Combatting Antibiotic Resistant Bacteria Initiative. Our expansion of our mission space—we have been very careful about not trying to present ourselves as the government’s drug development agency. We have a defined sort of national security mission. Antibiotic resistance, in toto, is clearly a public health program that crosses a threshold of significance that BARDA, you know, has been invited to take part, and instructed by the president to take part.

To date we haven’t taken on TB, for lots of reasons. And obviously there are many other agencies. And I have been neglectful in not mentioning our partnerships with NIAID and other governmental agencies that are trying to tackle TB head on.

BOLLYKY: Great. So we have by my count eight questions and six minutes. (Laughter.) So I’m going to go in groups of three. Again, ask them a short question. And then I’ll try to assign them to different speakers to see if we can get as many as we can.

In this group I have Libbie, John Lange, Jamie.

Q: Just quickly, I’m interested by the—oh, I’m sorry. I’m Elizabeth Prescott and I’m at National Defense University, the National Security Technology Accelerator.

I’m interested by the assumptions we put around the definition of countermeasures. So there’s always a presumption or predominately a presumption that that is a pharmaceutical or a biologic. Is anyone exploring tools that would be targeted—so I’m thinking data-driven tools, analytics, AI—that are not targeted at health systems, but targeted at the individual? And this gets back to the comment of, you know, whether we need a silver bullet, or an incremental improvement could actually get really substantial different outcomes.

BOLLYKY: Great. John Lange.

Q: Thank you. Having been the special representative on pandemic influenza for three years, 2006 to 2009, it was kind of depressing to see the decline in interested in that. And then it was Ebola that brought back that interest in the global health security agenda. But we’ve been talking mostly about a lot of kind of a U.S.-focused emphasis here. How do you see getting the world engaged? Because GHSA has about 60 countries, and that’s just a third of the total number of member states of WHO. Is it the international health regulations to be used as the basis for this, because of its surveillance capabilities, et cetera? Or are there other means to get the world behind this, including Russia, and Brazil, and some who are skeptical of GHSA?

BOLLYKY: Great. Jamie?

Q: Thank you. Jamie Yassif from the Open Philanthropy Project.

I’d like to follow up on the thread about medical countermeasure platform technologies, specifically around the issue of how do we drive down the timeline for producing a vaccine for a novel pathogen? And I think the metaphor of a rugby scrum is a very apt in this space and we’re trying to look at this space and identify gaps. It’s hard to know who has the ball. There’s a lot of money and there’s a lot of activity, but I don’t think we’re anywhere near solving the problem. So I’d be curious to hear both speakers take on where the open challenges and opportunities to engage to help move it forward.

BOLLYKY: Great. So here’s how I’m going to divide the answers. I’m going to have Steve talk about the data point. Steve already had a chance to talk a little bit about the global coalition. I’m going to ask Rich to take on John’s question. And then I am actually going to ask Steve take on the platform technology question, because Rich already talked a little bit on that.

HATCHETT: So just on the—John, really quickly, I mean, I think the SEPI (ph), the initiative that Steve talked about earlier, you know, actually grew out of the Ebola response, as you said. And the amazing and encouraging thing are the number of global partners that now seem to have a really legitimate and sustained interest in coming together to solve problems, and new partners. And so not just governmental partners that we’ve been talking to for years about flu preparedness or other countermeasure preparedness.

You know, we have been trying to position ourselves to support those efforts, and to help them succeed. But they face huge challenges. In terms of the world trying to organize it, it took the U.S. government a decade’s worth of learning from our own failures before we began to get our own internal system right. And it’s much easier to operate inside one government than it is to operate in a multilateral context. And so there is this impressive and, in my 15 years of doing this, unprecedented global interest in thinking about how to address these problems. But the challenges that the world is going to face are also very substantial, as you know.

BOLLYKY: Thank you. Data to enable individuals and platform technology.

DAVIS: So the answer’s sort of yes, but or no, but, because the fact is—it’s not a central thesis or piece of the work, I think, across—if you sort of do the quick landscape in general. I mean, a lot of focus still on the vaccines, the drugs, the diagnostics, sort of the traditional list. I would say the but is there is actually a renewed or new sort of conversation. Sort of let’s sort of go back through sort of tools and countermeasures kind of by user focus and, you know, so we often are focused on system users.

And now we’ve actually been, you know, much more at the frontline community health worker. And now there’s sort of a new set of conversations and activities about going back to the consumer at the—in the low-resource setting context, of not in, you know, just larger developing-country markets. So I think that that’s an emergent thing, and it will be driven by the digital tools available. So I think prospectively I’m quite optimistic, but it’s certainly not a big focus of any funding tranche or anything today.

The second is—so, I think the question is absolutely right, is that we still—we have sort of conceptually moved our way forward, but the practical issues of how to actually get this right is really hard. And if you’d sit in on SEPI (ph) conversations or—I mean, actually, even at PATH we’ve gone through a very, very major change taking—we have about—we have one of the largest vaccine platforms of anybody, including industry, in terms of the number of candidates, et cetera. But all of ours are for vaccines for which the markets are failing, right, or haven’t provided enough incentive to create industry to do it alone.

And trying to figure out how to trade—move that from a bunch of vertical programs to a platform, and figure out where the gaps are, what the function. We’ve invested a huge amount to get that right, you know, and it’s full of gaps. I think one of the gaps is the—you know, that we’ve still got this sort of funny place how regulatory—and I think this will be a critical issue—the regulatory piece of critical on this topic, is can we—and we can get all of the players in a room and get industry and civil society and government maybe talking to each other.

But if the regulators aren’t, you know, willing to even concede that there might be a different way of approaching this problem, we’ve got a bigger problem. But as you start going through that flipping, you’ve got to look at functions more than—I think the big flip is to talk functionally what needs to happen to get done, rather than pathogen by pathogen by pathogen.

BOLLYKY: Great. So we’ve run out of time, but I’m going to give Rich the last word, because Steve got two questions. So if you want to make a last comment, and then I will cut people loose.

HATCHETT: Yeah, no, just—well, thank you for setting this up. I mean, this is an audience that I don’t normally get to talk to. And it’s great to think about BARDA’s role in international responses. It’s clearly something that we’re going to be doing a lot more in the future, I think unfortunately. You know, we do need help in terms of thinking about what our role is going to be, and how to best prioritize and configure our efforts to address these international problems, particularly where the problems relating to health systems, delivery, and the need—you know, in the event of an actual event—the need to respond into environments that we are unfamiliar with, and not—you know, not configured to succeed in.

And so that is a multi-sectoral problem. And thinking about what it would take to succeed in responding to emerging infectious diseases seems to be a problem of the moment that’s in the part of the zeitgeist at the moment. I don’t think it’s going to go away. It needs a lot more attention than it has received previously. And, again, as Steve was saying, the investments here need to be appropriately balanced given the challenges we face with non-communicable diseases and more traditional infectious diseases. And we shouldn’t—our investment shouldn’t be driven by fear or by over-amplification of the threat.

BOLLYKY: Great. I’m going to end on that note. Please join me thanking the speakers. I apologize if you didn’t get a chance to ask a question. (Applause.)

(END)

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