Transformers: Health

Opening Remarks

MS. CORATTI: Hi everyone, welcome.

I know, I like it. Hello.

My name is Kris Coratti. I'm Vice President of Communications at The Washington Post, and General Manager of Washington Post Live.

I want to thank you all for coming to see Transformers: Health. We're really excited to have some of the top minds in health and medicine here with us today, including two titans of the health care industry, Dr. Anthony Fauci and Dr. Scott Gottlieb.

Today, our guests are going to offer us an inside look at some of the most cutting-edge health innovations and treatments that are really disrupting the medical field, today.

We'll spotlight how revolutionary technologies like augmented reality and 3-D imaging are being used for invasive medical procedures, and how they might completely transform treatment models in the years ahead.

We'll also examine some of the most pressing public health challenges, and hear about pioneering advancements and creative proposals for solving them.

And before we get started, I just want to thank our presenting sponsor, Pfizer, who you're going to hear from a little bit later in the program, as well as our supporting sponsor, the University of Virginia.

And now, I'd like to welcome to the stage former FDA Commissioner, Scott Gottlieb, and The Washington Post's Colby Itkowitz.

[Applause]

America's Health Care Future

MS. ITKOWITZ: Hello, everyone. Good afternoon. Thanks for being with us. My name is Colby Itkowitz. I'm a politics reporter here at The Post.

And I'm delighted to welcome my guest, Dr. Scott Gottlieb. As many of you probably know he is the former FDA adminis--Commissioner, rather, under President Trump. He resigned in April and has joined the venture capital firm New Enterprise Associates as a special partner focused on innovation and health care delivery.

So, I want to remind the audience that if you have any questions for Dr. Gottlieb, you can tweet your questions to us by using the hashtag, #PostLive.

So, let's get started.

DR. GOTTLIEB: Thanks.

MS. ITKOWITZ: So, Silicon Valley is betting big on health care. You've got Google and Apple and Amazon, which of course Jeff Bezos owns The Washington Post. I have to say that when I talk about Amazon. And they're investing big in the health care industry.

Is it going to take innovators like those companies to transform health care?

DR. GOTTLIEB: Perhaps. I think Google has a model like the old Bell Labs where they're experimenting for the sake of experimentation. So, they're doing some interesting things, not just Verily, but off of the Google Health platform.

So, if you look at what David Feinberg is doing at Google proper looking at their search technology and applying it to health care, I think there's a lot of opportunity for the applications of digital health and AI in this field.

I think with digital health, we're further along. We have a clear regulatory framework. I think with artificial intelligence it's still early days. I mean, one of the last things I did when I was at the agency in the last two weeks was get out that blueprint for how we would, you know, sort of envision the regulation of artificial intelligence medical devices.

I think with respect to the applications to imaging, those applications are here, but I think providing--applying artificial intelligence just more broadly to looking at health care information, trying to tease out things that can help both clinical development as well as providers, that's a little bit further away, at least from a regulatory standpoint.

MS. ITKOWITZ: Right. How did you envision regulating AI?

DR. GOTTLIEB: Well, with digital health, we recognized that those tools are so highly iterative that we needed to move towards a much different regulatory paradigm where, instead of regulating the devices itself, we would regulate--effectively, regulate the firms and allow firms to go to market with new iterations of their devices, or sometimes new devices altogether, if we can validate the underlying software architecture, but more importantly validate how they validated their own software. So, basically, approve their SOPs, if you will, their standard operating procedures, for validating their software.

Because we realized that the regulatory approach, we require premarket approval for every new iteration or every new product doesn't really apply.

With artificial intelligence, here, again, you have a self-learning device that makes modifications to itself and you have to allow--you actually have to allow a regulatory process that bakes in the fact that it's going to make mistakes. Now, that's a hard--that's a hard thing for a regulator to sort of accept, that there's going to be an error rate, but that's part of the AI device and part of the self-learning.

And so, part of the broad vision there is that what you would do is you would regulate them by making available publicly available data set that you would validate, and then you would ask sponsors to validate their tools against that dataset. And so, if they can demonstrate a certain competency, a certain clinical validity, a clinical utility, perhaps, against a publicly available dataset, that would be--that could be a big component of demonstrating, you know, effectiveness for regulatory purposes.

And the agency took a similar approach with next-generation sequencing, where they recognized certain publicly available datasets, one of which is maintained by the National Institutes of Health, as sort of the dataset that you would test against for the approval of a next-generation sequencing platform.

So, these are whole new concepts of regulation. I think for me the broader message that I was trying to articulate was that we were trying to look at new ways to regulate to accommodate the nature of the innovation we were seeing, as opposed to trying to apply the sort of standard regulatory paradigm to these new tools, and sometimes we were able to do that. Sometimes we had to seek legislation. So, in the case of in vitro clinical tests and even OTC drugs, over-the-counter drugs, we needed to go to Congress.

MS. ITKOWITZ: Yeah. I mean, I think this kinds of piggybacks off of that, but we're talking--precision medicine is a term that you hear kind of tossed around all the time. We're talking about cutting-edge treatment models for big diseases, and you made some strides at the FDA for creating a regulatory framework for precision medicine.

What else can the FDA do to accommodate kind of the more novel treatments to get them to market faster?

DR. GOTTLIEB: Well, I think the process is pretty efficient right now.

You know, you're seeing drugs approved on the basis of a small series of patients in the earlier stages of clinical development because you see the ability to deliver drugs to a very highly targeted patient population show overwhelming benefit in a small, sometimes heavily pretreated patient population.

On the gene therapy side, some of the issue--some of these products look so efficacious that, you know, you basically can have confidence that they're going to deliver a clinical benefit on the basis of relatively small trials.

There, the bigger issues are questions around sort of theoretical risks associated with the gene therapy. Are you going to have off-target effects? Does the sort of structure of the gene therapy construct, the vector that's delivering the gene change as you change the size of the gene, because that's--there's all these sort of longer-term theoretical questions. What's the durability of it? You're not going to be able to answer those with any reasonably sized clinical trial.

So, I think the whole development process has moved in the direction of allowing approval on the basis of a smaller series of patients because there's so much overwhelming evidence of effectiveness because the populations are being so highly prespecified, based on things like diagnostics that can look at patients on the basis of biomarkers that they express.

The bigger challenge, I think, is the commercial challenge, which is that when these products are getting approved on the basis of 30-40 patient clinical trials, sometimes an oncology or rare pediatric diseases, you have a commercial environment that's saying, "Well, that's not enough data. We haven't answered all the questions."

That's probably true. We haven't answered all the questions. We need to have robust, post-market follow-up, but when you have a significant unmet need when you're dealing with a pediatric disease that's going to create cumulative disability in a child, there's an imperative to try to get that out to the market more quickly, as long as you have, you know, a reasonable assurance of safety, that it's not going to create some untoward side effect.

MS. ITKOWITZ: When you say "commercial," do you mean that doctors--

DR. GOTTLIEB: Payers, payers.

MS. ITKOWITZ: You mean the actual patient--

DR. GOTTLIEB: Yeah, I mean--no, I mean the actual payers, the health plans.

MS. ITKOWITZ: The health--oh, the insurers, the insurers.

DR. GOTTLIEB: Yeah, so, one of the things I saw when I was at the agency was some Medicaid plans tried to move against paying for drugs that were approved through accelerated approval. CMS ultimately put out a bulletin saying you have to cover drugs approved through accelerated approval. The FDA has jealously guarded the idea that drugs approved through accelerated approval meet the statutory burden for safety and effectiveness and shouldn't be sort of perceived differently, but you've seen payers try to carve that out.

That's not a new phenomenon. I remember CMS trying to promulgate a policy back in 2003 when I was last at the agency to say, "Well, a drug approved through accelerated approval isn't really fully approved and therefore we're not going to cover it automatically."

But so, you're seeing payers doing things like that as a way to try to use the regulatory process, I think, as a gating factor to get more control over their own spending. I understand the challenges they face, but yeah, some of these products are targeting dreadful diseases.

MS. ITKOWITZ: Right. And speaking of dreadful diseases, I know that you are a cancer survivor, and my father currently is undergoing cancer treatment, and he has tapped into the integrative medicine side of treatment. And so, in addition to the chemotherapy that he receives, there's nutritional supplements, there's nutritional infusions through vitamin C and Curcumin and I wonder if you see a future where integrative medicine is accepted wherein those kind of supplements would be regulated by the FDA as medicine, as opposed to as a dietary...

DR. GOTTLIEB: Well, they can be regulated as medicine, if they want to. I think most of them would go the food route, the dietary supplement route, because they don't want to bring forward the evidence that they'd need to get--you know, finding of safety and effectiveness through a drug approval process and that's--therein lies the challenge.

I mean, look, I'm an empiricist. I think if people are making claims around these products, they should be bringing forward the evidence to substantiate the claims.

And on the dietary supplement side, there was a lot of challenges. I mean, the dietary supplement industry has evolved significantly from the days when DSHEA, the law that governs it, was first implemented. You're seeing a lot more--a vast industry, but creating more potential risk; also, taking more money out of the health care system.

And I thought at the time that I was at FDA and we put forward proposals for how we could apply greater regulatory supervision to some of those products, including, like, mandatory listing requirements for ingredients and better GNP requirements, manufacturing requirements.

MS. ITKOWITZ: But the idea of integrative medicine just generally. I mean, some insurance companies cover acupuncture, now.

DR. GOTTLIEB: Right.

MS. ITKOWITZ: I mean, the idea that there's a holistic health, a whole body to--

DR. GOTTLIEB: Well, I think there is a holistic. Yeah, I mean, look, I think, as a physician, I think there is a holistic approach to health care, and I think the sort of nexus between mental health and physical health is very tied, too. And patients going through a difficult diagnosis like cancer, you know, taking care of their mental health is exceedingly important to a good outcome.

I think, for me, the hardest part of my diagnosis was the uncertainty associated with it, and the emotional uncertainty of not knowing the outcome, not knowing what treatment to select, not knowing how the treatment was going to affect me.

And so, I think, as physicians, we need to pay attention to that. That's one component of the integrated health.

I mean, another component are the sort of non-traditional approaches to health care. Look, I think some of them show promise, but you know, you need to be careful because sometimes when you're applying a dietary supplement or some of these other things it could potentially interfere with the drugs, too. I mean, some of these potentiate metabolisms, slow it down, and could actually interfere with the chemotherapy.

And you know, as a physician, I saw things. I practiced in Elmers [phonetic] Queens, you know, which was a community of a lot of immigrants, and they would be taking other things when they came in and I used to see very weird side effects that weren't associated with the treatment they were receiving but were associated with something else that they were taking that they wouldn't necessarily disclose.

And so, you've seen--I've seen the other side of this and the challenges they can pose.

MS. ITKOWITZ: Yeah. So, I want to ask you, a few years back, you were doing some consulting for Pfizer; is that accurate?

DR. GOTTLIEB: I worked with Pfizer, in the past, before my time in FDA, and more than likely going to be working with them again in the future.

MS. ITKOWITZ: Yeah, so, we had a story that we reported last week about a Pfizer arthritis drug called Enbrel. And so, here's the background: Pfizer researchers had found that the anti-inflammatory drug appeared to reduce the risk of Alzheimer's. But after much internal review, Pfizer didn't see that Enbrel showed promise for Alzheimer's prevention, so they didn't move to any clinical trials, but they also did not share any of that data with other researchers, which some are wondering why not.

Pfizer says they would have pursued this if they believed there was solid scientific rationale to do so. What is your reaction to that story?

DR. GOTTLIEB: What's the business model when you do an article in advance of one of these things where your sponsor--I'm just kidding. Sorry, I had to do it.

Look, I read the article. It was based on a retrospective analysis of payer claims datasets. You know, those are, I think, highly speculative. You need to be really careful when you draw conclusions from payer claims data.

I always at FDA encouraged more sort of signal finding and the use of payer claims data to try to do datamining inside the agency. We did it particularly on looking at post-market safety, but sometimes we would look at ethics questions, too. But there were a lot of signals generated all the time that we thought were highly speculative and didn't follow up on because there was no other confirmatory evidence, or, you know, the dataset that we were working with was not that reliable.

So, I think you need to look at the underlying dataset to draw a conclusion there. The reality is anti-inflammatories more generally have been looked at over a long period of time. And I think it was well known that they had been looked at to see if there could be an effective Alzheimer's--I think people generally have concluded that's not the case. There's other TNF inhibitors on the market that, you know, had ample opportunity to study these indications and chose not to. Obviously, Humira has a lot of years left on patent life. And so, I have a hard time believing that someone stumbled across a cure for Alzheimer's disease and tried not to follow it up.

But you know, it opens up a more interesting question of doing sort of a very exploratory analyses off datasets that are very dirty, and what do you do when you have a signal that you think is not really even hypothesis-generating, you don't believe it's a real signal. Do you have an affirmative obligation to publish that or follow-up on it? I think the answer is no. I think you have to make a judgment.

I think that it depends on the setting. I think if it's a safety question, probably the bar is a little lower to speak about it; depends on the veracity of the data. But if we impose sort of a cultural expectation that every time someone does an exploratory study with a retrospective analysis of a payer claims database, they're going to have to publish it, I think you're going to close down a lot of, like, just sort of tooling around with data that could be actually advantageous.

MS. ITKOWITZ: Is there also a concern that people would hear about this with--and try to go take Enbrel off-market and--

DR. GOTTLIEB: Potentially. I mean, you're damned if you do and you're damned if you don't. I don't know how the--I don't know how the press would have perceived the company if they had published this in some, you know, publication and would that have been perceived as, you know, trying to instigate use of Enbrel.

Now, mind you, I think the company just had rights to the drug ex-U.S.--not in the U.S.--I think it's another company's drug in the U.S.

But that said, you know, I remember--and I don't remember the TNF inhibitors in particular, but I remember there was discussion around other anti-inflammatory drugs and could they be effective in Alzheimer's because there was a perception that some of the basis for that disease ideology was an inflammatory process. And so, it had been sort of picked over and thought about and there had been some studies done with various anti-inflammatories--at least small series of studies. So, it wasn't--at the time, I don't remember this being a novel concept. So, I'm sure that's the basis for why they even bothered to look at the payer claims data, or at least part of the basis.

But not having looked at the data, it's hard for me to really draw a conclusion about how believable is it. But again, I'm a skeptic, and part of that skepticism is that I think if a company had stumbled upon data that looked convincing in the biggest indication that could possibly be addressed by a new therapeutic, I'm having a hard time believing they would walk away from that.

You know, and Enbrel has gone--there is biosimilar competition to Enbrel, but it hasn't fallen off a cliff. It's still, I think, a pretty lucrative market for the people who are marketing those products.

MS. ITKOWITZ: So, my colleagues and I are working on a series this year called "The Fentanyl Failure." We're documenting the government's failure to address the opioid crisis, specifically the rise in Fentanyl. It kind of came out of nowhere and spiked and suddenly we see tens of thousands of people dying.

DR. GOTTLIEB: Yeah.

MS. ITKOWITZ: And although the President has said the opioid crisis is a top priority for the administration, you know, the deaths continue to rise. The Fentanyl is still making its way into heroin; now, it's making its way into meth. I mean, what is the big public health idea to tackle this?

DR. GOTTLIEB: Well, you know, I think that--I think it's an important observation that the nature of the opioid crisis is evolving.

I mean, this was a crisis formed through medical addiction, and the early addiction which we were very slow to address and always one step behind the curve in this burgeoning epidemic from a policy standpoint was being driven by Vicodin, Percocet, primarily the short-acting--the immediate-release formulations of opioids, but the long-acting formulations and the higher dose.

I think that it's evolving to one more of street drugs. To your point, Fentanyl--not just Fentanyl--you know, Fentanyl that's being sold as pressed Fentanyl, that's being sold as, you know, Vicodin, Percocet online but is really pressed Fentanyl.

And I think as it--and more of the new addiction--and what we are seeing is more of the new addiction is being formed from people whose first exposure is actually street drugs. And I think as that happens, as the addiction crisis migrates to that, you're going to see more overdose deaths, because people are now using street drugs and they're getting a super-potent formulation of Fentanyl in what they think is a Xanax that they're buying online and they're dying overnight. They're using as parties--at parties.

So, we have to recognize that the nature of this addiction crisis is evolving very rapidly. And we have been guilty for a very long time of always fighting the last fight and being slow to recognize how these things are evolving. And we're still sort of focused from a policy standpoint on the medical prescribing, and we shouldn't lose our focus on that, but medical prescribing is going down and it's being dwarfed by the flows of Fentanyl coming in.

We looked--when I was at FDA, we looked at seizures as a proxy for flows--which is a poor proxy, because you don't know if seizures are going up because you're doing better interdiction work or it's going up because there's more flowing across the border. But the growth in seizures dwarfed the decline in medical prescribing.

And so, we also struck a collaboration--I signed an MOU with Customs and Border Protection right before I left where we are going to work with Customs--or the FDA is now going to be working with--have to be careful about "we." The FDA is now going to be working with Customs and Border Protection to look at the seizures. And CBP will make available to FDA a certain representative sample of seizures, FDA will test that to determine what the potency is. And instead of just reporting seizures in pounds, which is historically how Customs and Border Protection report seizures, it's going to be reported in morphine equivalence. So, you're going to know the total amount of actual narcotics coming in, in terms of its potency and not just in terms of its pounds. That's--I think that's going to be mindboggling once that data comes out.

It's the kind of thing that someone's going to open up the newspaper one day and they're going to say, "Did we give permission to do this?" You know, like--and we struck the MOU and this is--we announced it when we did it and talked about it. But I think once that data gets reported it's going to be eyepopping.

And the other thing I'd say is the agency that does more interdiction work is actually the Coast Guard; it is not the Customs and Border Protection. So, a lot of those seizures are done at sea, and we weren't even looking at that data; we were just looking at CBP.

Am I running down the clock?

MS. ITKOWITZ: We are, and I have 17 Fentanyl follow-up questions that I don't have time for, but I do want to ask you, what innovations out there are you most excited about? What do you see coming down the pike that you think could really transform the health care industry?

DR. GOTTLIEB: Well, certainly the curative potential of gene therapy which is now--you know, when I was last at the FDA, there was no products approved, and I don't think there was anything in development back in 2003 that was worth speaking about, past phase one. And now, you're seeing approved products, and not just approved products, but a very rich pipeline.

I think we're in the early--very early innings of cell-based regenerative medicine and actual, like, legitimate cell-based regenerative medicine, not these clinics that are popping up and doing things, trying to skirt regulatory oversight. So, I think there is a lot of opportunity for curative potential.

And I am still of the opinion that some of these sort of unloved categories, like anti-infectives, I think there's going to be a lot of opportunity for new mechanisms, new markets, there.

And so, you know, I was placing bets in the sector which I guess I am now, I'd be looking there, too.

MS. ITKOWITZ: Okay. Great. Well, unfortunately, that's all the time we have for this segment.

But thank you so much Dr. Gottlieb, for joining us.

DR. GOTTLIEB: Thanks a lot. Thanks for having me.

MS. ITKOWITZ: And pleased stay seated as we move on to the next portion of our program. Thank you.

[Applause]

Bringing Clinical Trials Into the 21st Century

MR. BROW: Good afternoon. I'm Matt Brow, President of Avalere Health, a company owned by Inovalon.

And I'm proud to present to you our next panel on bringing clinical trials into the 21st century.

I'm also pleased to be joined by Rod Mackenzie and Donna Cryer.

Rod is the EVP and Chief Development Officer of Pfizer. In this role, he is personally responsible and leads 6,000 global team focused on mid- to late-stage clinical trial development of medicines.

He's also on the board of ViiV Health Care and also TransCelerate.

Thank you, Rod, for being here.

MR. MACKENZIE: You're welcome.

MR. BROW: And glad to introduce to you Donna Cryer, patient--patient advocate and attorney. She's the CEO of the Global Liver Institute, and also currently serves as an interim Executive Director of the Patient Centered Research Foundation [sic].

She is a graduate of both Harvard and Georgetown Law School, and dedicates her time to assisting folks with liver disease and improving liver health.

Thank you both for being here.

MS. CRYER: Thank you.

MR. BROW: So, while we're here to talk about improving clinical trials and the clinical trial process and moving that into the 21st century, why don't we hit upfront some of the things that Dr. Gottlieb and his interviewer were talking about just a moment ago, since we have the head of development for Pfizer, here.

Rod, do you want to give any comments about the recent Washington Post story and the disparate kind of reactions that we've seen from the general public and the scientific community.

MR. MACKENZIE: Yes, and thanks for the chance to comment on this.

Let me say upfront just how disheartening it is to read a story like this, because it so fundamentally misrepresents what we are about and who we are in our organization.

Our purpose is breakthroughs that change patients' lives. I think we all know--every Pfizer colleague, everyone in this room, knows people who are afflicted with Alzheimer's disease. It touches more or less every family. And we also know just how tough it's been to find new therapies. So, if we really believed that we had a robust, new, scientific hypothesis in this area, of course we would have published it.

To suggest otherwise, frankly, is just untrue. So, of course, we did not have a robust scientific hypothesis. What we had, as Scott Gottlieb explained, was really a simple observational analysis of insurance trial data, claims data. And that simply does not reach our scientific standard for publication. That's why we didn't publish it, that's why we won't publish it, because, frankly, it would simply create false hope.

What we did do was we paid for a clinical study that an investigator wanted to do. And unfortunately, like pretty much every Alzheimer's disease study, it was really unsuccessful. It did not validate the hypothesis. It was inconclusive at best, and there were no statistically different effects with the placebo and the active drug, and that's a shame. I wish it was very different.

So, I won't say much more about the analysis, because I think it's been pretty well worked in the scientific literature.

What I would say is that the public reaction to this is a little bit ominous because I believe that the mistrust that's created between the science and medicine community and the public is, of itself, a public health issue, as we will hear about later on today when we talk about the measles outbreak.

MR. BROW: Thanks, Rod.

And that's a good segue to what we're actually here to talk about today: For a lot of people in the room and in the audience, most likely, that don't live drug development day-to-day, I think it might be helpful to have a little bit of a refresher on what it is that you and your team and folks just like you are doing.

MR. MACKENZIE: Well, we're the D in R&D. We are the group that sits between the laboratories where most medicines are identified and invented, and the patients who need these medicines.

And what we need to do is we need to collect information of a quality and standard that will convince regulatory health authorities around the world that this is a drug that's safe and effective, and is available then to the patients.

So, we work with many, many people, mostly our patients, who are pioneers; whether clinical site investigators around the world, with the regulators, of course; and we have so many scientific disciplines within development that all come together to create what, in the end, is a body of evidence, the weight of which is that our medicines are safe and effective.

And if we do that well with high quality, then these medicines can make it to patients.

MR. BROW: Thanks, Rod.

It sounds like there's a pretty significant structure built around this concept and this process.

But Donna, maybe you can talk a little bit about how it could be better. Why should we modernize this process in--of drug development?

MS. CRYER: Well, we've made great strides. Certainly, it's been exciting to work with companies like Pfizer on this process of research and development, to find new treatments and cures for patients in liver disease.

But basically, you know, make it as simple as possible, the R&D needs to be faster so that cures move more quickly to people who need them. There need to be more of them so patients have choices, and so that the diversity of people, whether it's genetically or otherwise, is reflected in the medication so that every patient has the opportunity to get the best drug for them.

And then, finally, R&D can be better. So, I look forward to the second generation, the third generation, not just the first drug to market so that, again, we can, you know, refine and see the improvements.

And it's really not--it's so often represented as a, you know, one-direction pipeline, but it's really a circle of evolving and improving. And, as a patient and patient advocate, it's been very gratifying to be invited into that circle.

MR. BROW: Thanks, Donna.

So, Rod, as one of the largest, at least, sponsors of clinical trials in the world, what is Pfizer doing to help modernize clinical trials in the drug development process?

MR. MACKENZIE: Well, first of all, let me say that clinical trial--the way clinical trials are done has been rather successful over the years, but it hasn't really changed very much over the last 50 or 60 years.

We are making dramatic changes, I would say, now, and it's a result of several things.

The first is that health care technology has reached a level I see of quality and robustness that it can actually be used for the first time in a broad sense in creating regulatory quality datasets.

The second is we're very committed to change. We've committed to taking at least 50 percent of our operational timelines out of all the clinical development that we do over the next three years, but just simply getting better inside our company and the way we do things and our processes, and all of our colleagues are committed to that.

And then, finally, it's all about the relationships we have. Patient groups, like Donna represents, we're listening very hard to make that a much better experience for them and for the site investigators, and for everyone else involved in the process. And historically, we've not done as much as that.

MR. BROW: Yeah, let's drill down on that a little bit, because I think a lot of people most likely have an impression that the patient role in the clinical trial is as a passive subject, somebody to be tested and to gain data from.

But could you guys talk a little bit about what's the appropriate role, and what's today's role of the patient in a clinical trial?

MS. CRYER: Sure, it's much beyond just being the subject in a trial. And in fact, for the Global Liver Institute, we actually have a policy that we don't help, you know, share information and recruit for trials where patients--it doesn't have to be us--but where patients and communities were not actively engaged in helping to develop to create and craft that trial.

So, patients and people, and communities as a whole, have started to fund trials. So, they give the money for trials as venture capital sometimes; provide the data for trials. Those patient registries explode.

And then, in the type of work that the Global Liver Institute did, we--you know, I've had the privilege of both, you know, advising at a very broad level in terms of patient engagement across the R&D function, as well as very specifically in our work in fatty liver disease and NASH on things that aren't just, you know, nice-to-haves or social goods, but really things that have impacted the protocols so that patients actually wanted to participate in them and they were accrued faster.

So, that saved time and money for everyone--and that the informed consent was actually informed and was able--structured in a way that people really felt that they understood the trial process that they were involved in, and it actually went through the Institutional Review Board, or IRB, faster.

So, being able to show those very tangible ways that patients and partnerships with patient advocacy organizations can improve the quality, can make the clinical trial experience better, not just for patients, but for all of the stakeholders involved, including industry, is really exciting.

MR. BROW: Is there anything else about that experience with the NASH Study that you'd like to share?

MS. CRYER: Well, I think it's in--the fact that it's an ongoing effort. So, it wasn't just a, you know, one-time and done, that it was both holistic and longitudinal.

And frankly, as an attorney, they did leverage all of my expertise. And so, I not only got a chance to work with the medical affairs team but went back and was able to talk through with the legal and compliance team about appropriate ways to work with patients in a variety of ways, you know, that were appropriate and novel, and moving much towards the way that pharmaceutical companies and others have traditionally worked with physician, or KOLs, and now positioned patient opinion leaders, or POLs, are in the same name--and we need to have a contractual and structural and ethical frameworks for that in the same way, and being able to work towards that was great.

MR. BROW: Rod, would you say that this kind of patient engagement and interaction is becoming the new normal for Pfizer?

MR. MACKENZIE: It's completely the normal. In fact, we will not start a clinical trial unless we have been sitting down with patients, working through their needs in a clinical trial protocol, listening to them, incorporating their feedback, and making it something, as Donna said, that they want to take part in.

We see the clinical trial participants as pioneers; they're essentially citizen scientists, helping move medicine forward.

So, for example, we will simulate the entire protocol before we even start it to see that it--what we think in theory will work actually works in a practical setting.

We talk to patients. We give them the feedback on the trial. We tell them what happened in the trial. We say thank you, a very simple but powerful thing, for participating; and we tell--we give individualized feedback, as well, of which they can then incorporate into their medical records, so that we're trying to make our clinical trial research part of just another care option that physicians can use when they're working with patients.

So, it's so fundamental and central now to what we do.

MR. BROW: Thanks, Rod.

Please.

MS. CRYER: And I think that change of actually making it a part of the business, part of the operations, was really essential, making sure that no protocol can go through unless it includes how it--patient insights and shows how they have been included and incorporated. That really is a key differentiator. Because it's moved it from something that's sort of nice to do to something that is part of someone's job and things can't move forward without it. So, that was imperative.

MR. BROW: Thank you.

We have only a couple minutes left, but Rod, I wanted to touch on something you mentioned earlier in the discussion.

Talk a little bit, if you can, briefly, about--both of you, please--about the rise of technology in drug development and the use of--what's the promise here to improve in modernized clinical trials?

MR. MACKENZIE: Well, I think there's many areas in which it can impact. Let me give you a couple.

One is that we can make clinical trials much more convenient for patients, because by using certain types of technology--and we've just started to work with Verily on this area--we can make clinical trials remote so that people can take part of the trial without necessarily having to visit a research site at inconvenient times that can interfere with their life.

And so, by doing that, we actually expand the clinical trial population. We expand the diversity of people who have the opportunity to take part in clinical trials. Because right now, only a small percentage of people ever do that, who are qualified. So, that's one area that is going to make a huge impact.

The other is in the quality of the data, just automating the data collection and how it's transferred from database to database, ultimately into regulatory dossiers, is an opportunity that I think will increase speed and the quality of what we do.

MR. BROW: From the patient perspective?

MS. CRYER: From the patient perspective, anything like--exactly what Rod described, to bring the clinical trial closer to the patients, to their home, is important.

The other important aspect I wanted to mention is that the more holistic data, new types of data that can be incorporated into trials from wearables, for example, or sleep, or just patient diaries, other types of patient-generated health data and real-world evidence so that we really understand the fullness of people's lives and new types of data outside of the clinic walls that haven't been incorporated before.

MR. BROW: Thank you.

Donna, if you could give to this audience your call to action, what do you want them to take away from today?

MS. CRYER: Well, on June 11th, it would be remiss of me if I didn't remark that tomorrow is international NASH day, June 12th. And so, more information for that is available on www.globalliver.org, including how we train patients to be more proactive partners in research.

MR. BROW: Thank you.

And Rod, I will turn it to you for closing, your final words.

MR. MACKENZIE: Yeah, I would ask people, visit Pfizer.com. We have "find a trial" on there. There's an application, you can see what trials Pfizer is actively running. Of course, clinicaltrials.gov, which contains all the clinical trials and gives you the opportunity to see what's available to participate in a clinical trial.

MR. BROW: Thank you.

MS. CRYER: Thank you.

MR. MACKENZIE: Thank you.

[Applause]

Augmenting Reality: The Changing Face of Medicine

MS. ZEZIMA: Good afternoon, everyone. I'm Katie Zezima. I'm a national correspondent for The Washington Post. I'm really thrilled to introduce my guests here today. We have Dr. Brian Gastman. He's a plastic surgeon at the Cleveland Clinic. Dr. Gastman led a team of 11 surgeons in performing this successful facial transplant in 2017, and Katie was the youngest person ever to receive a facial transplant.

And also with us is Karl West, director of medical device solutions at the Cleveland Clinic. Mr. West is one of the Clinic's lead innovators. He was in charge of spearheading the use of new technologies in this surgery.

So we hope you can join the conversation. Please tweet at us with the hashtag #PostLive. So, Dr. Gastman, first question is for you. You know, this was a pretty groundbreaking transplant. I know there have been a number of facial transplants at the Cleveland Clinic. Katie Stubblefield was the youngest transplant recipient in U.S. history, 11 surgeons and you were the lead. You know, by the time you saw Katie, it was about six weeks after the trauma had happened. How many surgeries had she had on her face? What makes this face transplant different from the others that have occurred both here in the U.S. and abroad?

MR. GASTMAN: Thank you. I think there's a number of unique aspects to Katie's story. Obviously her age was part of it. One thing that we see many times in these patients is that they've gone through multiple reconstructive surgeries before they ever come to us. And as such, we're dealing with patients who not only have had other physicians treating them, where it's hard to know exactly what happened, but many of them have gone into deep depression, opioid addiction, and other negative social factors that makes their case very difficult.

One of the reasons that we were able to be successful with Katie is that we got to her so early in the process. Her youth was both a positive and a negative. It was positive because we all know that younger people tend to heal better. On the other hand, we also know that transplantation in younger patients tend to have a higher risk of rejection. There's many reasons for that, and these gave us a lot of pause into moving forward.

But ultimately, it was really her story that was so impacting on us personally as physicians--not just us physicians. I'd say the nurses, everyone. It was very hard to see someone that might be your daughter--I literally have a daughter her age--and to treat her and to eventually sort of her become part of the family, if you will. And so for all those reasons, she was a really unique case. We are just very happy that she did as well as she did.

MS. ZEZIMA: And given the complexities of the surgery, what were some of your biggest concerns going into it?

MR. GASTMAN: Well, the surgery, it was more than just an event. It was really a process. Probably the biggest concern we had was finding the right donor for her. And now we're talking about after we've sort of got through the scary parts of dealing with someone who had had an injury to her brain and her face, and all the reconstructed efforts that required to get her to a safe point. The donor part took, I think, 15 months of us evaluating multiple different, unfortunately young women. And even then, we had one false alarm. That was probably the most difficult, because we didn't know what we were going to give to her. Would it be someone who was much larger or much smaller, already more aged? Maybe other deformities. We didn't know how she and her family would handle having a new face. I think that was by far the most challenging part.

MS. ZEZIMA: And Mr. West, let's talk about the technical innovations involved in the transplant. It was done with some pretty unbelievable technology. It included augmented reality, 3D imaging and 3D printing. Can you tell the audience kind of what augmented reality is, and how it was used in this procedure?

MR. WEST: Sure. So, augmented reality is we took Katie, right? And what we were able to do is superimpose images onto her using this is what we call a HoloLens. This is a device you can wear on your head. And it allows the surgeon and the physician, the caregivers to still see the environment around them, including Katie. But what we're able to do is project different images onto Katie, different scenarios, say, of the different type of cranial structures, maybe how much they wanted to take or what they didn't want to take. So it allowed the physicians to look at different scenarios on the fly.

MS. ZEZIMA: And you see in this video you kind of--you work it by kind of going like that. Can you explain a little bit how you make it work and kind of what it is more that you see when you're in there?

MR. WEST: Sure. The idea of this, it's a computer. It really is. So what we do at the Cleveland Clinic is we develop these different applications. What the beauty of working in the Lerner Research Institute is that we have access to the end user. In this case, it was Dr. Gastman and some of the other ones, Dr. Papay. And so it was that interaction that allowed us then to take these goggles and to download information on to it that they could use.

MS. ZEZIMA: Dr. Gastman, what was it like for you using that? Have you done something like that before? And as a surgeon, you know, what was it like to kind of add all this technology into what you were doing?

MR. GASTMAN: It was new. It was absolutely new. The way I was raised, if you will, in surgery was to use what we call axial scans, where there are just cuts across the patient, and then you in your mind had to sort of put that together. Then later we had what was called 3D imaging. And really what you see is a rebuilding, if you will, of the skeleton. But all we see is the outside. We can move it around, flip it upside down, but that's it. And still you had to use your mind's eye between those axial cuts to know what was going on on the inside with what you see on the outside. With this technology, we can actually go within the actual patient's and the donor's anatomy and see what's going to happen from the inside's perspective and how we're going to connect some of those inside, if you will, structures to the other patient.

MS. ZEZIMA: Yeah, because you kind of see in the video a little bit of that, a little bit of that going on. Speaking of 3D, Mr. West, there's 3D printing involved, right? Can you tell me a little bit how that played out in this surgery as well?

MR. WEST: So 3D printing, what we do is we take the CT datasets. They're DICOM datasets of Katie. And what we did then was work with the physicians and we selected out what the very important information is that they needed to have in their hands. So it provided them this physical model that they can look at, especially the vascular structure. I don't think you realize how much of that was actually transplanted from one person to another. And what the 3D-printed models allowed them to have a model of Katie and then also of the donor. And then they can physically look at these. And then along with the HoloLens, it provided just a tremendous amount of information.

MS. ZEZIMA: And those are the skulls right there, right? The 3D-printed skulls, yeah.

DR. WEST: Those are some of them, yes. We had multiple prints.

MS. ZEZIMA: And, Dr. Gastman, how did you get trained to use this? I put it on earlier, and it's amazing. You can kind of see everything. But it's very complex. So how did you get trained to do this?

MR. GASTMAN: Well, Karl and his team, we actually have a number of students that work with him and us together as collaboration, and they actually teach us how to use it. And then we come up with ideas how we can help apply it to not just face transplant but other--especially in our line of business--creating a facial reconstruction.

MS. ZEZIMA: In terms of cranial facial reconstruction, since this is your specialty, how helpful has it been in terms of other procedures and other things that you're doing?

MR. GASTMAN: Well, we've been using three-dimensional modeling for reconstructive planning and the development of plates for some time, as well as those type of models that you see there. This is really an emerging technology. It's something that I would still call it experimental. What it has done, though, is opened our minds to how we are going to operate on the future patient. We're no longer going to--what we thought was really cool and new three years ago is already old, and this has really changed how we look at creating a facial reconstruction.

MS. ZEZIMA: And Mr. West, is it becoming more commonplace to integrate technologies like this into medicine? Kind of how are you getting this into what physicians and nurses and everyone at the Cleveland Clinic is doing every single day?

MR. WEST: Some of the beauty of working at a research institute that's directly linked to a hospital is that we spend a lot of time in the ORs working with the clinicians. And as engineers and scientists, we start seeing some of the limitations. Right now, if you think of minimally evasive procedures right now--right?--so years ago you would have spent possible weeks in a hospital after some type of open procedure because of infections. Well, now we can do minimally invasive. We do everything through your arteries.

The problem is you don't see anything, right? You see everything on your ultrasound or fluoroscopy. Using these goggles and the applications we developed at the Cleveland Clinic is it provides kind of x-ray vision to the physicians. I mean, vision is the most important thing that the surgeons need. And this provides a 3D image of 3D anatomy. So this allows them to, first of all, see things better, perform, and more accurately perform.

MS. ZEZIMA: And how long does it take for you all to fine tune it and make sure it's working well before it actually gets into the hands of the clinicians?

MR. WEST: Well, it's a lot of back-and-forth. I will say that. It takes a team. There's a great team at the Cleveland Clinic that we have, and we've worked for many years on developing image guidance. So it's not just the goggles, but we're also using the goggles to track devices that we're placing in the body as well, so for everything from aortic repair to tumor ablations.

MS. ZEZIMA: Can you talk about that? Like, how do you do that?

MR. WEST: So aortic repair, aortic aneurisms, think back before we did endovascular procedures, we'd have to cut the patient open and then we would cross clamp the aorta. We would cut out the bad section and put the new section in. Now what we can do is come up through the leg. And it's like a stent. It just pops open inside.

But when you do these procedures, you're using fluoroscopy. It's a 2D image of a 3D problem. So now what we've done is we've taken the patient's image, CT datasets, we can download all that into the computer. And then any of the devices that are placed inside the body we track using electromagnetic tracking, and all that then is displayed on the HoloLens, including ultrasound. So now the physicians, the caregivers looking at the patient, right where his hands are working--not at a screen somewhere else--at his hands, he can see the patient's anatomy and everything that's going inside, that the device is being placed inside at that time. So it's real time.

MS. ZEZIMA: Right. You can see the holistic picture rather than just the 2D of a 3D problem.

MR. WEST: Right. And just like you did earlier, you tried it on, and you can walk around the patient, right? So you're able to look at the patient from many different angles, angles that you would never get with the standard of care that we have right now.

MS. ZEZIMA: Yeah, it's extremely interesting to know all the different--are there any applications where it's worked--beside the aortic--but any other areas of medicine where it's worked particularly well and others where it hasn't worked quite as well and you're still trying to figure that out?

MR. WEST: So one of the areas we have a small IRB evaluation going on at the Cleveland Clinic where we're using it for tumor ablation in a liver right now. You know, ablation, cryo and microwave ablation works very well if you can get to where you need to be in a tumor, and what's what we're doing right now. We're guiding the surgeon to where they need to be within that lesion to do a very good, a very complete--it makes a good kill zone of the whole. To tell you the truth, we haven't had many areas that we haven't been successful in. Those are just kind of the main ones we're picking out right now.

MS. ZEZIMA: With the tumor, it kind of helps you bore down to exactly where you need to go.

MR. WEST: Yeah, you can preoperatively, if you can go in, look at the images of the patient and say this is where I need to be, this is where I need to be when I do the ablation, I can guide you to that. This technology will guide you to that position.

MS. ZEZIMA: The theme of today's program is innovation. What do these disruptive technologies mean for innovation in medicine? Are we kind of just looking at the tip of the iceberg here, or kind of where do we go from here with this?

MR. WEST: And I think Brian can attest to some of this, is that I think the HoloLens--and not just the HoloLens, but I say holographic guidance and using holograms is going to change medicine drastically, right now. I think it's going to allow us to perform procedures faster, more accurately over time. It is providing 3D imaging. I mean, this is the piece that's been missing for a long time, and views that you cannot get right now with the standard of care. I've been told by some physicians that this is going to change medicine like x-rays changed medicine at one time.

MS. ZEZIMA: Wow. And how about you, Dr. Gastman? How do you think this is changing innovation, especially since over the course of your career seeing the evolution of this?

DR. GASTMAN: Well, holographic technologies like this are also part of a spectrum of wearable technologies. And so one of the things that it is doing right now that's disruptive is, in the sense of--in a positive way, of course--is education. So for instance, when I put on some type of image assessor on my head, I can actually show those I'm training the surgeon's view. When you see what you see here, this is what most people are seeing from behind me, right? It's maybe a bird's eye view, it's a side view, but it's not really the surgeon's view, what they're dealing with, the challenges that they have. Having things that are literally in our view as a wearable technology opens the door from the people that we want to train to see what we're seeing. Adding what this has really augmented reality to it also has an educational component to it, because now those who are learning how to do these very complex surgeries can actually do these surgeries without actually having to touch a patient. They can see how accurate their surgery was and then be assessed until they're really ready to do it on their own.

MS. ZEZIMA: So you say this is something that's being integrated into medical schools right now, for residents? Tell me a little bit about that, how you're kind of teaching this younger crop of surgeons to use these types of things, but just through their regular training.

DR. GASTMAN: Well, Karl probably could tell you, but this started, I believe, as a collaboration for the medical school

MR. WEST: Yes.

DR. GASTMAN: You may want to mention that.

MR. WEST: Well, so the Cleveland Clinic has its own medical school, and the idea is to kind of do away with cadavers and do more of this type of augmented or virtual reality. With these different technologies, we can place the students in different scenarios that you can't get just on a cadaver. I think the other piece of it is that's really important is telementoring, is that a surgeon that maybe not performs procedures a lot, right--maybe somewhat in the early stages--a more senior surgeon across the United States or on the other side of the world can put these goggles on, and together they can communicate through these goggles and perform the procedure.

MS. Z: That's pretty amazing. We've only got two minutes left. So last question. Is there any concern about safety and security issues with these emerging technologies like AI and machine learning?

MR. WEST: Well, I think there always is. I will tell you from our standpoint at the Clinic, we're research. We're at the very early stages of this, and we're working with the clinicians. You know, this technology will eventually go into companies. In fact, there's two companies already formed now, the Cleveland Clinic, with this technology. Then that burden is going to be more placed on those companies at that point, I think. But there always is a concern, right? Because this uses the internet, and that communicates. So we have to have secure networks. So I think there's going to be a lot of work in that area.

MS. ZEZIMA: So unfortunately that's all the time we have for this segment. I could ask you both questions for the rest of the day on this because it's so fascinating. But thank you so much. I want to thank Dr. Brian Gastman and Karl West for joining me. And now we will move on to the next portion of our program. So thank you so much.

[Applause]

Chasing a Cure: The Global Outlook on HIV/AIDS

MR. BERNSTEIN: Good evening, everyone. I'm Lenny Bernstein, a health and medicine reporter for the Washington Post. We are privileged to have with us today Dr. Anthony Fauci. He leads the National Institute of Allergy and Infectious Diseases at NIH. As you know, he's one of the world's best-known and widely respected experts on HIV/AIDS. Over the past 40, 50 years he is one of the few people in the world who've had the most influence on transforming HIV from what was essentially a death sentence when the virus was discovered, to a manageable chronic disease which it is today.

I wanted to start with that transformation. I've heard you speak, and you give a very cogent sort of description of how far we've come. I remember I was covering the University of Connecticut back in '81 or '82 and activists started to show up, and they started to say, look, there's a disease out there, we don't know what it is, and we don't know what to call it, but it's going to kill you fast if you're not careful.

DR. FAUCI: Right.

MR. BERNSTEIN: Can you tell us about the period in between?

DR. FAUCI: Well, I first got involved with what would turn out to be HIV/AIDS before it had a name. We used to call it, inappropriately, gay-related immunodeficiency. And certainly, before we knew what the etiologic agent was. So from 1981, when the first cases were reported by the CDC, we began admitting patients at the NIH in Bethesda. And that period of time of mystery and concern about dealing with something that you don't even know what it is, but it's killing young, mostly gay men, was really surrealistic. I write about it and talk about it as the dark years of my professional career and even in my life, because you're a physician, you're trained in healing people, and everybody that you're taking care of is dying and they're all young. That was very frustrating.

MR. BERNSTEIN: What was the survival, length of survival?

DR. FAUCI: Well, the median survival was about 12 months, namely 50 percent of the patients who came in to see you would be dead in about a year, and maybe 80 to 90 percent in two years. The reason that was the case is because AIDS is a disease, HIV, that takes many years to get somewhat advanced. We would only see the patient when they were deathly ill because they didn't know they had HIV infection because we didn't know it was HIV, and so we had no diagnostic tests. And so the only time you would have someone come into a hospital is when they already had advanced disease. So from the time you saw them to the time they died, the median survival was about 12 to 15 months.

MR. BERNSTEIN: What is it now?

DR. FAUCI: Well, right now it's really, totally transformed, because what's happened over the years until we now have like a combination of three drugs which you can take in a single pill. So if a 20-plus-year-old person comes into our clinic--in fact, Lenny, even in the same room where I saw them 38 years ago--if a 20-plus-person comes in recently infected and I put them on the extremely effective drugs that we have available right now and they stay on that drug, you could look them in the eye and tell them by the actuarial curves that if they their medicine, they can live an additional 50-plus years. So if they come in in their 20s and, all other things being equal, they live another 50 years, they could live almost--not quite--almost a normal lifespan.

There will be other complications because when you're infected, particularly for a long time, there are things that create chronic problems with organ systems. But if you get caught right away, reasonably soon after inspection, and you get on drug, it's completely different than it was in 1981. Completely different.

MR. BERNSTEIN: There were all kinds of predictions that HIV was going to be apocalyptic, hospitals weren't going to be able to cope with the number of patients. None of those obviously came to pass. What happened?

DR. FAUCI: Well, what happened is that science--and if you look at the investment that we have made in biomedical research, the discovery of the virus, a diagnostic test to determine the extent--but importantly, of all the things that are scientific advances in the arena of treatment have been nothing short of breathtaking. You know, in 1987 we got the first drug, which was AZT, which when we gave it to individuals, the level of virus came down modestly, but not durably. So we were very excited that we first had a drug.

But if you know anything about an RNA virus, and HIV is an RNA virus, RNA viruses tend to mutate very easily. So you knew sooner or later it was going to mutate away from the effect of the drug.

Then a few years later we had a combination of two drugs, and then the transforming year was 1996, when with the advent of a certain kind of a drug called a protease inhibitor, we realized that if you give patients three drugs in combination--and back then it took many, many pills, 15, 20 pills--you could get the level of virus to below detectable level, and it stayed that way as long as they took their drug, because the virus had no opportunity to mutate because you were completely suppressing it. And a virus can't mutate if it's not replicating. So that was the beginning of the transformation where, as you said, we refer to it as the Lazarus effect because people who were dying and thought they were going to die would get up and then say, gee, now what am I going to do with myself? I'm going to have to go back and live my life. That was transforming.

And now today, up to 2019, it's gotten even better and better because you can give a person one pill that contains three of those drugs, once a day, and it will do the trick of what was done with many, many pills before.

MR. BERNSTEIN: I want to talk about the pills in a second, but just briefly, if we can raise our gaze outside of the United States, what has happened in Africa and other parts of the world that almost seems as miraculous?

DR. FAUCI: Well, what happened is that from 1996 to 2002, 2003, it became so clear that you could really save the lives of these individuals and they would live relatively normal lives. But what was happening is that 90 percent of all the HIV infections are in the developing world, and 67 percent are in Sub-Saharan Africa.

And it was really the vision and the action of the United States President George W. Bush, back in 2002, called me into the White House and actually the words that he used was, as a rich nation, we have a moral obligation to see that people who were born in certain areas and regions of the world, that they should not die and suffer because they happen to be born in Sub-Saharan Africa. So can we go there and figure out, can we put together a transforming program that would get treatment, prevention, and care? And is it feasible to do it in the developing world, in Sub-Saharan Africa? There were a lot of people who felt, oh, you can't do that in Africa. It's just so underdeveloped you couldn't do it. You know, there was probably a bit of subconscious racism in that, to think that you couldn't do that.

So we went there. We scoped it out, came back, and we said we think we can do it. And the President, to his great credit, said, okay, put the program together. We did, and it's ultimately now called the President's Emergency Plan for AIDS relief, or PEPFAR. So PEPFAR's been active now for 15 years. Fifteen million people have received antiretroviral therapy. So that means at least 15 million lives have been saved; 2.5 million babies were born uninfected who otherwise would have been born infected.

MR. BERNSTEIN: Because their moms are on--

DR. FAUCI: Because their moms are on therapy and they're blocking the transmission to the baby. So the developing world, it sounds like a rosy picture. We still have major challenges ahead, because there are still 36 million people living with HIV and there are about 12, 13, 14 million who are not yet on therapy. And that gets to the point of the will of implementing the exquisite scientific tools that we have. PEPFAR has gone a long way. The Global Fund to Fight AIDS, Malaria, and Tuberculous, the United States pays about a third of that tab and the other countries come in. Those are the things that are making the developing world not the catastrophe it could have been.

MR. BERNSTEIN: And in the United States, how many people have HIV?

DR. FAUCI: There are 1.1 million people living with HIV. About 750,000 have already died of HIV. And the thing that we really need to address--and we are, because we recently inaugurated a program to try and end the epidemic in the United States in the next 10 years, by 2030--but there are about 38,000 new infections each year in the United States. That's bad. What's even worse is that it has been essentially that way for over a decade, 10 to 15 years. It's come down a little bit, but not substantially, and that's what we've really got to aim our efforts at over the next five to ten years.

MR. BERNSTEIN: So you brought it up. Another president, rather unexpectedly, has said we are going to end the transmission of HIV in the United States, and we're going to do it in 11 years.

DR. FAUCI: Right.

MR. BERNSTEIN: Is that realistic? And if it's realistic, how are we going to do it?

DR. FAUCI: I think it is realistic, and the reason is--and this is something that over a year ago, Bob Redfield, who is the CDC director, and I spoke about because Bob is someone who's career was devoted to HIV/AIDS before he came to the CDC. And we began talking about the feasibility of doing this. And somethin­g just jumped out at us, and that is that we have the treatments that we know that if you treat a person who is infected with HIV and you bring the level of virus to below detectible level, not only would you save the life of that patient. That person will not transmit the virus to their sexual partner. It doesn't happen. And we've done tens of thousands of people we've watched.

Number two, you have an implementation of what's called preexposure prophylaxis or PrEP. So if I'm at very high risk of getting infected and I take one pill a day, I can decrease by 97 percent the likelihood that I will become infected. With that as a background, we have what is called a concentration of focused hot spots. So in the United States, the numbers are stunning. Twelve to 13 percent of the population is Africa-American. Of the new infections, between 45 and 50 percent of the new infections are among African-Americans. Sixty-five percent of them are among men who have sex with men. Seventy-five percent of them are in young people 18 to 35. So we have a demographic concentration.

But the thing that really blew us away, Lenny, is that if you look at the map of the United States, there are 3,700 counties in the United States. All these little boxes of counties. Forty-eight of those counties, plus the District of Columbia and San Juan, account for more than 50 percent of all the infections in the United States.

MR. BERNSTEIN: That is stunning.

DR. FAUCI: Forty-eight plus two out of 3,007. So we have a geographic hot spot and we have a demographic hot spot. So it's a question of the will--political, economic, medical, et cetera--to go out and do it, and that's the reason why we think we can do it.

MR. BERNSTEIN: So when you say tools, you mean the medication, Truvada, PrEP, and it's a question of getting it to people, keeping people on it--because you have to take it every day to keep your level undetectable, and sort of following through.

DR. FAUCI: Right.

MR. BERNSTEIN: But medication adherence in general is terrible, and we can't stay on our blood pressure medications.

DR. FAUCI: Right, exactly.

MR. BERNSTEIN: So how are we going to keep these folks on--

DR. FAUCI: Lenny, it's a combination of adherence once you're on it. But with this situation, something that's even more problematic is access to the people that are the most vulnerable. Because if you look, it's concentrated in these counties in the southern states. It's mainly African-American men who have sex with men. There's an extraordinary amount of stigma against those people. And when they get stigmatized, they are reluctant or even can't get access to a healthcare system that will both educate them, test them, and get them on therapy if they are infected and get them on prevention if they're not infected. So stigma is really a major obstacle to getting this done, unfortunately.

MR. BERNSTEIN: If we could wipe out stigma as an issue, we still would have sort of a group of folks who live on the street, who are intravenous drug users, who are really the toughest group to deal with. And then we haven't even mentioned rural America. There's a bunch of states where it's also hard to get medication to folks in rural America. How do we do that?

DR. FAUCI: Well, we do it by accelerating our effort in involving the community. What we've learned and part of the plan that we've put together, the 10-year plan, is to go out and really embrace the community. The CDC has actively been doing that. They're going to accelerate that. We're going to work with them with our Centers for AIDS Research. HRSA, particularly the Ryan White program, who has been very effective in getting drugs to people and keeping them on drugs and suppressing the virus. It's just going to take a ratcheting up of the effort. It's not going to be easy for the reasons that you've pointed out.

MR. BERNSTEIN: Are we going to bring it to them? Are we going to bring the medication to them on the streets?

DR. FAUCI: Well, you know, it's very interesting, because one of the models that we're using is a program that was started in San Francisco, which is called the RAPID program. They proactively go out into the community--homeless shelters, gay bars, on the street. They get people tested. They have a test that can actually get a result in 20 minutes or so. If you know somebody's infected, you give them the medication, and you say here's a month's worth of medication. Start taking it, get back to us in a month and we'll get a prescription filled for you.

MR. BERNSTEIN: And the number of new infections in San Francisco is way down.

DR. FAUCI: Way down.

MR. BERNSTEIN: Way down, as a result of this program.

DR. FAUCI: As a result of the program. That's a model. New York state, with Governor Cuomo, is trying to copy what's gone on in San Francisco, and it's starting to go down in New York. We did it right here in the District of Columbia, which at one point was very, very bad with regard to incidence and prevalence. It's starting to come down now because of a concerted community-based effort. That's what you have to do.

MR. BERNSTEIN: What about cost? Truvada is an expensive drug, although it is not expensive to make, but it is expensive. I think the list is about $1,600 a month?

DR. FAUCI: Right. It's about $20,000 a year at the retail price.

MR. BERNSTEIN: At the retail price.

DR. FAUCI: Right.

MR. BERNSTEIN: So is that an obstacle?

DR. FAUCI: It is an obstacle, and that's the reason why a number of negotiations are going on now between the government and the people, Gilead, that make Truvada. Soon it will be a generic. But even before it's a generic, we need to get the price down. They have offered to give free to people who don't have health insurance, 200,000 people for 11 years, giving them drug for free if they don't have insurance. But we still have to get it more manageable from a price standpoint.

MR. BERNSTEIN: If I have insurance, I'm on the hook for the co-pay, not for the whole thing.

DR. FAUCI: You said it.

MR. BERNSTEIN: Co-pay is high?

DR. FAUCI: That's the problem. Even if you have insurance, the co-pay is a problem.

MR. BERNSTEIN: Gotcha, okay. We have a couple of minutes left. We went fast.

DR. FAUCI: We did.

MR. BERNSTEIN: Is there an HIV vaccine in our future? There's a lot of research going on. Is that a feasible thing? Is that going to happen?

DR. FAUCI: I think it is. I think it's not going to be easy and it may not be a classical vaccine. When you think about vaccines, for example, the measles vaccine, even though unfortunately we're in the middle of a measles outbreak because people don't take the vaccine, but measles vaccine is 97 percent effective if you get two doses of the live attenuated. I don't think that is in the cards for us with HIV, because HIV is such an unusual virus that the body does not readily make a very good immune response against it. So a vaccine tends to mimic natural infection to make you get an immune response to protect you. Natural infection doesn't induce a good immune response. So we're going to have to figure out a way to do better than a natural infection.

MR. BERNSTEIN: Wow.

DR. FAUCI: However, given all the other things we have, treatment as prevention, preexposure prophylaxis, those kinds of things, I would settle, Lenny, for a 55-60 percent effective vaccine. Because if you combine that with the other modalities of prevention, I think we could put the nail in the coffin of the epidemic. So I think it's in the cards. It's not going to be easy. We have two major large trials going on in southern Africa right now, with a candidate that showed some promise in a trial that we did in Thailand several years ago.

MR. BERNSTEIN: I'm going to squeeze in a Twitter question. It's from Katharine [phonetic]. It was recently reported that a 16-year-old who died in 1969 may have actually died of AIDS much earlier than the first reported cases. The tissue samples were destroyed in this case. Is there any update on that case, and is there any work that can be done to investigate how this person contracted the infection?

DR. FAUCI: Yeah, well, this is something that has been quite argued back and forth, that someone way back when was--but the circumstances of that individual, never left the United States, was in an area of the country that was--I'm not so sure that that person had AIDS. And if they did, it was a one-off and it doesn't have any impact on what's going on. So it's kind of nice to speculate, but it doesn't have any impact.

MR. BERNSTEIN: Okay. One more. A second person was recently reported cured of AIDS, I guess, of HIV.

DR. FAUCI: Right.

MR. BERNSTEIN: Can you explain the circumstances there, and whether you feel this is really a cure?

DR. FAUCI: Well, it is a cure for those two people, but it's very unusual. It's a situation that there's a genetic defect of the expression of the receptor that the virus needs to bind and infect you, and there were two people, one in Berlin, one in London who had AIDS and they needed a stem cell transplant because they had a leukemia or a lymphoma.

MR. BERNSTEIN: In addition to AIDS.

DR. FAUCI: In addition to AIDS.

So they needed a transplant. So they found a person who had the genetic defect that would not get the cells infected, and they gave the person the stem cell transplant from that person to them, and that person then had cells that the virus couldn't replicate in. So that person was now cured. That's really good for that person, if you really need a stem cell transplant. The second patient was from London. It's completely non feasible for the 36 million people who are infected with HIV. So it's a proof of concept, that you can cure. But as something that is applicable on a large scale, it's not.

MR. BERNSTEIN: Gotcha. All right, we're out of time, unfortunately. I want to thank you, Dr. Fauci, for being with us again, and we're going to move on to our next panel, which is focused on the measles epidemic.

[Applause]

Innovative Solutions for a Public Health Emergency

MS. SUN: Good afternoon, everyone. I'm Lena Sun. I'm a health reporter at The Washington Post on the national staff. I'm delighted to welcome my guests here today. We're going to be talking about the measles outbreak in the United States and some innovative solutions to public health crises like this. So to my left is Dr. Oxiris Barbot, the New York City health commissioner. Next to her is Dr. Nancy Messonnier. She is director of the CDC's Immunizations and Respiratory Diseases Center. And next to her is Dr. Peter Hotez, a dean and professor at the Baylor College of Medicine. You can join our discussion by tweeting to hashtag #PostLive.

So let start off by talking to you folks about where we are now. Measles cases are at their highest level in 27 years. CDC's latest update shows there were more than 1,022 cases reported as of Monday. And before we talk about the innovative ways that you guys are going to address this problem, I would like to ask the panelists to briefly talk about how did the U.S. get to this point. And maybe we'll start with Dr. Messonnier first and then Dr. Barbot and then Dr. Hotez.

DR. MESSONNIER: Sure. So immunization coverage in the United States remains high. Ninety-four percent of kids are protected from measles by the vaccine. But we live in a global society, and internationally, measles is spreading at an increased rate. Unvaccinated Americans traveling abroad get exposed to measles, and they bring it home with them. But in most cases they bring it home to communities that have high vaccination coverage, and the health department rapidly responds and we see maybe a case, maybe two.

But this year they brought it home to communities with low immunization coverage, and those communities were very susceptible to measles outbreaks. Most of the cases we've seen this year are associated with two outbreaks in New York City and New York state. While there is disease elsewhere in the United States, it is really those two large outbreaks that are driving the large numbers of cases this year.

MS. SUN: Dr. Barbot.

DR. BARBOT: So in New York City, we're currently up to 588 individuals that have been diagnosed with measles. And as Dr. Messonnier mentioned, our immunization rates across the city are very high. Our public school children have a 99 percent vaccination rate. And what that translates into is we have more children in New York City vaccinated against measles than the entire population of Boston, of San Francisco. We have over a million children in our city. The issue is that, as Dr. Messonnier mentioned, we had an individual who brought in measles from abroad into a community where we had isolated pockets of schools with lower vaccination rates and a high number of exemption rates for the measles. And so that then created the perfect storm for having to tackle one of the most contagious, if not the most contagious virus on the face of the earth.

MS. SUN: Dr. Hotez.

DR. HOTEZ: So, Lena, in 2017 I wrote an article saying that it's inevitable that measles is going to return to the United States. So I think the 2019 measles epidemic in the U.S. was both predicted and predictable. And that has to do with the fact, from my perspective, being in the state of Texas--I'm a vaccine scientist who develops vaccines for tropical diseases. I also have this interesting family life. My oldest daughter Rachel has autism and other developmental disabilities, and for years I've been countering the major central tenant of the anti-vaccine movement, claiming that vaccines causing autism and explaining what autism is and how it's absolutely impossible that vaccines cause autism.

What we saw in Texas was scary. We saw the steep rise in the number of kids not getting vaccinated because of phony reasons, because the anti-vaccine lobby had become so dominant in the state of Texas and we had 60,000 kids not getting their vaccines. So when we took the time to look to see is this isolated in pockets in Texas, or is it nationally. And ultimately, we identified 15 urban areas where there's large numbers of kids not getting vaccinated. So even though nationally, as both of you point out, we're doing great, there are these pockets where large numbers of kids are not being vaccinated. So we identified 15 urban areas, and now seven of them have measles in 2019. So that is the problem, that the anti-vaccine lobby is very aggressive and very successful in a pyrrhic sort of way in those 15 or so urban areas.

MS. SUN: I want to ask Dr. Barbot about this, because you have been quite outspoken about the situation in New York and calling out the anti-vaccine groups. What specifically are they doing, and how are those actions affecting immunization rates?

DR. BARBOT: So the way that I look at this is, as New York City's doctor, it's my responsibility to protect the health and safety of our population. And when there is a threat propagating false, dangerous information, we have a responsibility to counter it. So what has been happening in isolated pockets of our community is that these individuals have been targeting households with robocalls, with frightening information, false information about the measles vaccine. They have been distributing pamphlets. They have been holding rallies. And so we have been very vocal to say this information is not only wrong, it's dangerous and it's irresponsible in an outbreak for these individuals to be so callous and putting people's lives at risk. And so we have been very vocal in countering those messages.

And one of the things, I think, that has helped us in this endeavor is that not only have we as the health department and as the city have been vocal, but we have had partners who have used our content to then have face-to-face conversations with families. Because at the end of the day, what we're most interested in is having families feel good about vacating their children and understanding the safety and the efficacy of vaccines, because it's not only important to ensure that these children are vaccinated now, but that children from here on in continue to have high rates of vaccination.

MS. SUN: But this measles outbreak in New York City has gone on for now, what, eight months almost? And it has been very difficult to get your arms around it. I know you've done a lot of work. Do you think there needs to be a more robust innovative way to be more pro-vaccine and get that message out there, use the same tools that they're using? And if so, who should lead it? And I would like each one of you to answer that question.

DR. BARBOT: So I think we have been extremely aggressive in countering this outbreak. And we issued a public health emergency at the beginning of April. And when we look at the main numbers of new individuals diagnosed with measles as compared to April, we've cut that number in half. And so that is an indication, along with the fact that we have vaccinated over 50,000 people against measles, is also another indication that we are making headway.

The one thing that I will say, and that I said earlier today, is that in terms of countering this, we have relied heavily on community partners that are from the affected community more than we have in the past, because I think that we are countering not only the anti-vaccine messages, but fears that these communities may have about government involvement. And what we are focused on is ensuring that we provide the most accurate information and then we're agnostic about who the messenger is as long as it lands the way that it's intended.

MS. SUN: Dr. Messonnier.

DR. MESSONNIER: Yeah. I think one lesson that we learned in New York City, but we learned repeatedly, is that when myths and misinformation take hold, it's hard to stamp them out. It becomes deep-rooted in people's beliefs, and it's hard to counter it. So what we of course want to do is get there first and get the right information to people to counter the myths before they start believing in them. There is a way in which innovation can help us to identify communities at risk and can help us be more tactical in how we use social media. So innovation would be great. But in the end, as I think you've heard, it is really about those day-to-day conversations, sitting down with the parent and having those conversations.

Nationally, we know that despite all the questions parents have about vaccines--and I think it's natural in today's society, with so much information available, that parents would have questions. But parents still trust their own healthcare provider most to help them make healthcare decisions. And just like in New York, in any community that we work with, in many cases, the most effective communicator to a parent is somebody who is from the same community, who already has built a trusting relationship because they're part of the community, they're a local public health authority, or they're their healthcare provider. So those local conversations, answering those questions, being able to provide science to counter the myths, really has to take place in front of the parent. It can't be just innovated.

And I think that speaks to maybe your larger question. What do we need to do nationally? National action is great. I think this measles outbreak this year has really prompted a national conversation and lots of visibility in the issues, and we should continue to have that conversation. But in the end, it really is about local action and us empowering our local and state health departments and our clinical partners, professional organizations to have those conversations with parents. There's really no substitute for that.

DR. HOTEZ: I certainly agree with those remarks, but I would take it a step further. And I've been recommending a three-part solution to solving this problem and to prevent future measles epidemics from happening in the U.S. The first is the recognition that the anti-vaccine movement has become a media empire. The estimates are there are now 500 misinformation websites out there, anti-vaccine misinformation websites, all ramped up on Facebook and other forms of social media. The Amazon site is basically an anti-vaccine site now. My book which I wrote called "Vaccines Did Not Cause Rachel's Autism," the good news, that's probably the highest-ranked pro-vaccine book on Amazon. The bad news is, overall, it's ranked number 20 because there's 19 phony anti-vaccine books actively promoted. We need to figure out how to dismantle the media empire.

The second piece to that is, they've now acquired a political arm. So in multiple states like in Texas, like in Oklahoma, like in the Pacific Northwest, there are political action committees that are raising money to lobby state legislatures to make it harder and harder to vaccinate our kids, and easier and easier to exempt out, and that's why we've had so many problems nationally. So we've got to dismantle both the media arm and the political arm.

And the third is we need to build a more robust system of vaccine advocacy in this country. But if you just do that alone, it's not going to counteract the dominance that the anti-vaccine movement now has on the internet and through their political action committees.

MS. SUN: So then following up on that, one has to assume, unfortunately, that this is not going to be the end of measles outbreaks in the United States. And before the next one happens, or to prevent the next one, do we need to have some more innovation in the legal approach by public health authorities and pull out some of those other tools from the toolbox that New York City has used? Or is that too close to government mandate?

DR. BARBOT: Do you want me to go first or--

MS. SUN: Yeah, you can go first.

DR. BARBOT: So I think that the tools that we have in New York City have demonstrated that they are making a difference. And our response is characterized by leveraging those public health hammers, if you will, along with a strong social media presence, countering messages, and then good old-fashioned public health. One of the things that we are just starting to do is we are partnering with the Jewish Orthodox Women's Medical Association. We are putting them together with the Visiting Nurses Association, and we are offering people in-home vaccinations.

MS. SUN: Is it free?

DR. BARBOT: The Health Department will pay for it. So it's free to the individuals, but we'll pay for it. And so what I was telling my staff is, you know, I never thought that in my public health career we would be giving immunizations on the downlow, right? And so but whatever it takes, whatever it takes.

MS. SUN: Innovation, right? That's innovation.

DR. BARBOT: Exactly. And so it's not just about the high-tech. It's about the low-tech as well, and working with communities.

MS. SUN: Would you like to weigh in, Dr. Messonnier?

DR. MESSONNIER: What I would say is that every outbreak that's going on right now in the United States and every outbreak that went on last year and every outbreak that's going to happen next year is actually different. And it's really hard to have cookie cutter solutions, even in New York City and New York state. While there are some similarities to the outbreaks, there are actually lots of differences because the local contexts are different.

So CDC's role is to work with the local and state health departments to empower them, to provide them data.

But it would be, I think, incorrect to assume that the exact same things that work in one location would work in another. We do take lessons from one to the other, and we continue to build the evidence and the data so that next year we'll be better-equipped. Our tools will be sharper. We have developed a toolbox to help our local and state health partners, as well as the clinicians.

But one important thing for me is this is not just about preventing this year's measles outbreaks. It's important to stop these outbreaks. It's hugely important to stop these outbreaks. But you have to take a long-range view. And our long-range goal is to make sure that the public maintains--and if they've lost it, to reestablish their trust in the U.S. immunization program. That's really important for the long-run. Because for me it's not just about getting them the measles vaccine. It's getting them all the childhood vaccines so that they can prevent 14 childhood vaccine-preventable diseases.

MS. SUN: So just to follow up on that though, they are very effective because they use these heartbreaking emotional testimonials, right? And people see those and they listen to those. Why doesn't the public health community do more of that same strategy and tactic and make some of those?

And when we had the anti-smoking campaign, remember those? That campaign was very effective, and it came from the top and it came from all sectors of society.

DR. MESSONNIER: Do you want to talk about your experience?

DR. HOTEZ: Well, you know, I absolutely agree. And that's why I felt compelled to speak out about why vaccines don't cause autism. Here I am a vaccine scientist and a pediatrician. I'm also the parent of an adult daughter with autism. If I'm not going to speak up about it, who will? And that has met with some success being able to tell that person's story.

But you know what is really interesting about the New York epidemic is that's the one we didn't predict. So we predicted seven measles outbreaks in the U.S. just by looking at declines in vaccine coverage locally. The one we totally missed was what happened in New York. And I think we know why. Because we never counted on deliberate predatory behavior by the ring leaders of the anti-vaccine movement.

You know, Lena, you were the first to report in Minnesota how leaders of the anti-vaccine movement went in and targeted the Somali immigrant community in 2015, 2016, 2017 and told them the phony story about claiming vaccines cause autism, got vaccine coverage to drop from 90 percent to 40 percent. And guess what? There was a measles epidemic.

I think the similar set of forces are happening in New York, the phony documents, the robocalls, the phony teleconferences, the townhall meetings. At what point do we say that this isn't right, that we can't allow leaders in the anti-vaccine movement to basically perpetrate purposeful fraud which has now resulted in 40 Jewish kids in the hospital, including 12 in ICU? Actually, I don't know if they're all kids, but 12 people in the ICU because of this. So this is serious stuff, and we have to figure out a way how to counteract it.

DR. MESSONNIER: Maybe if I could just add?

MS. SUN: yes.

DR. MESSONNIER: I think we have to understand that how people get their information has changed, and it's going to keep changing. And as a parent myself I can tell you that I'm inundated with health information, and it's difficult to sort through it all. It is true that folks that are strongly opposed to vaccine have been very tactical in how they use social media to get their messages across. However, I would also say that there are promising developments in that space with multiple of the social media companies wanting to work now with public health and the medical community to try to make sure that the scientifically accurate information comes first.

I do agree, though, that it is difficult when there is anecdote and science, it's difficult to counteract the anecdotes with science. And our strategy, I think, needs to be to make sure that parents have access always to scientifically credible information so that when they hear stories that really tug at the heartstrings, but they have a reason to think that doesn't sound exactly right, they know that there's a place that they can go for scientifically credible information and that they continue to trust their healthcare providers and the public health leaders can make sure they're getting accurate information.

So I don't think it's a matter exactly of quid pro quo, although I admire people who are out there giving their personal stories. But I do think it's about ensuring credible scientific information, in any format that people want to get access to it.

MS. SUN: So we have a Twitter question. I will just ask maybe Dr. Messonnier to answer it very quickly.

"Are there any ill effects at all from vaccines?" This person would like to know.

DR. MESSONNIER: Vaccines are very safe and incredibly well-studied. And it's because vaccines are studied not just before they're licensed, but also really in perpetuity, that I can say with confidence that the U.S. vaccines are very safe. We have a myriad of ways that we look at vaccines, study them. But we also have oversight committees that look at our data to make sure that what we're doing is credible. That's true for the CDC. It's true for the FDA. It's true for the World Health Organization. I have kids myself, and they're vaccinated. I certainly wouldn't vaccinate them unless I was sure that the vaccines that they're getting are very safe and very effective. The best way to prevent measles is through the measles vaccine.

MS. SUN: Well, I think I'm going to wrap up here because I think we're running out of time. I'm looking at the time. And I want to thank all of you for joining today, Dr. Oxiris Barbot, Nancy Messonnier, and Peter Hotez. If you'd like to watch any of the interviews from today, including selected highlights, head over to WashingtonPostLive.com and you will be able to get all of them.

Thank you very much

[Applause]

[End recorded session]