This is the stage where I should normally give my disclaimers about any kinds of stocks or things like that, but I'll have to give a disclaimer that I'm not a treatment person. I am part of the Division of Metabolism and Health Effects. And so we treat the organ and tissue damage associated with, which is why I'm here at the liver meeting, rather than the other aspects. And I give thanks to Lori DeSharm. Did that, let's see. Have I got a pointer here now? How do I get the pointer? It's pointing here. Yeah, is it because, pen and laser pointer. Probably not. And now you have it, perfect. Okay, so Lori DeSharm was a program director with the Treatment and Prevention Group, and she prepared most of these slides. She's moved on to a position elsewhere at NIH, but she was gracious enough to provide me with the slides and let me stand up here and be a robot and try and do my best to take you through them. Yeah, okay. Yeah, got it, that's the easiest way. So NIAAA is kind of unique amongst institutes within NIH, and that is because we do have a full spectrum of alcohol research. It's less disease-specific and more like, we treat everything. There's neuroscience, there's metabolism and health effects dealing with the organ and tissue damage. There's epidemiology, prevention, medications development, and behavioral treatments. So as we recognize the fact that alcohol use and abuse are oftentimes decisions that our people make, sometimes they're more prone to become an alcohol abuser, but we do recognize that there's a wide range of things that have to be studied. And about half of our budget goes to the neuroscience. We get about 20% for organ and tissue damage. Epidemiology prevention gets about 20%, and medications development and behavioral treatments get about 20%. So the budget is split, and we have to be aware that it's an important constraint upon what we do is to split that budget and use it to the best of our ability. There are five goals that have been laid out for the strategic plan for NIAAA to identify the mechanisms of alcohol action, pathology, and recovery, to improve diagnosis, to improve prevention strategies, and to develop new ones, to develop and improve treatment strategies, and to enhance the public health impact. So in that, the epidemiology and prevention group has been outstanding in producing materials for the web to put out there for the public to see, and they come up pretty readily when you do a search. I'll talk about that a little later. Specifically, these mission statements have been modified by me to include and to incorporate a couple of things that I think are important to emphasize as far as the division of metabolism and health effects, and that is that we don't just direct support biomedical and behavioral research. We also have an agenda that includes the need to devise effective methods for preventing and treating alcohol use and abuse, and for dependence, as well as the consequences, and the consequences are the things that can kill people, the liver disease, and so forth. Now, as I mentioned, there are a number of materials that have been produced by the epidemiology and prevention group, including the Youth Screener, the Clinician's Guide, Medication's Guide, the Rethinking Drinking, and the Alcohol Treatment Navigator. I'll go through those quickly with you and spend a little bit more time on the Treatment Navigator. So basically, these are all available through the NIAAA website. You can, if you have a loved one or you yourself are interested in reading these materials, it's a good source of information where you can determine whether your child, your nephew, your friend has a need for an enhanced sort of intervention. So the Youth Screener is one of these for detecting risk at an early stage. It includes ways of evaluating your friend's drinking and your children's friend's drinking. So the Clinician's Guide, excuse me, the Clinician's Guide is a tool that's aimed more toward the professional. Medication's Guide, and the Medication's Guide, we'll talk a little bit about that later on, but that's very important, especially if an addiction specialist is treating someone with acute or even mild liver disease, they need to be aware of the interactions of the drugs, and so there's often a need to have a hepatology consult to go along with that to make sure that they don't choose a medicine that's on the forbidden list. Rethinking drinking is a big hit that came out about five years ago, I think, and it came with much fanfare and has been loudly applauded as a support mechanism for quitting. And then we get to the Treatment Navigator, which is organized very nicely. It's aimed more toward individual self-help and how you can find a treatment provider. It's kind of stepwise. You can step right through the entire website. You can, if we look at these, I think these are gonna pop up one at a time. So what to know about alcohol treatment, what is it? What is the disorder, how do we define it? And there's considerable argument and discussion in the community about what is someone who needs to have an intervention and at what cost and so forth. It provides you with a way to find alcohol treatment so that you can, it in fact has a search spot here where you can put in your zip code and you can look for somebody, you can evaluate their credentials, find out how they are, and maybe some feedback on what the provider is like to work with. And what questions to ask, but you need to ask, sometimes you need to ask some very specific questions. One provider might not fit for every individual or every age group. So these are all here on the web. Let's see. And here you get some tips on questions you should ask, like what sorts of things do you need to ask? You need to find out what their credentials are, whether they are a member of a professional organization, whether they have their sociology degree, whether they're a psychiatrist, psychologist, all those things are important in terms of determining how they deal with you. And I found that interesting. We had a presentation at NIH a few months ago by one of our leading scientists, and he was DiClemente Roberto, I think, isn't it? I forget his first name, I'm sorry. He was talking about the difference between a lapse and a relapse in alcohol use, and he chooses to use the term lapse as opposed to relapse if it's a relatively short-lived, kind of a couple of drinks and you move on. And then the community, of course, argues about whether a lapse is the end of the world or whether it's something you should take as part of the program, and he takes it as part of the program that the lapse is important if you are learning from it and recommitting to your program afterwards, it's probably helpful. If it means that you descend into a well of self-pity and self-loathing and continue drinking for years afterwards, then that lapse truly is a relapse. Okay, so this is all to point you toward the treatment navigator, and the easiest way that I found, I just did it on my phone yesterday while I was sitting in the audience. I thought, how hard is it to get there? And I found that if you put in treatment navigator, well, you get a lot of things, but NIAAA's website comes up about the fifth down. If you put in treatment navigator, NIAAA, it comes up a little faster, a little higher up. It's not the first thing that comes up, but it's there and it's easy to find, and maybe it's easy to remember, too, that the treatment navigator is there. And if you can't find it there, just go to the NIAAA website so everybody can spell that. I hope everybody here knows how to spell NIAAA. So, and this was part of where we were looking at searching for treatment programs. You can put in the zip code, find programs near you, find people. You can actually, they give you a, in this thing, they give you a chart that you can fill out and you can indicate all the different people that you've considered as your therapist, to take care of your needs, and the pluses and minuses under a number of categories, whether they take your insurance or not is probably a pretty important one. So, that's it for the treatment navigator, and what I'd like to emphasize to all of you here is that I'm not a treatment specialist. I kind of stumble through this a little bit as much as anybody else would, and the yellow down here addresses the treatment navigator. This is the website, hcpsalcoholtreatment.niaaa.nih.gov, but if you don't like the type and you're like me, then you just put in treatment navigator NIAAA and it comes up about the third or fourth thing in Google, so it's really easy to find. Now, this is for me and the rest of the division at NIAAA. I don't know if Kathy is here or not. Kathy, are you here? No. So, I'm not the director of the division. Kathy Young is the director of the division. I am a program director within this division, and we do the entire spectrum below the neck, basically, the organs and tissue damage and things like that, but where that affects the inflammatory processes that affect the addiction, that's a kind of a crossover between the neurosciences and our division, and we fight over that money, but please, if you are interested in working in liver, you have to remember that 70% drink and 30% drink to excess, so why aren't you looking at alcohol? And then you should give us a call. And my name, Gary.Murray at NIH.gov. I'm happy to field anybody's inquiries, and if you have an inquiry about the treatment navigator, you can send it there, too, and I'm pretty fast about responding. If I don't know what to do, I'll find someone who will, so I encourage you to get in touch with me. If you're out here and you're a younger scientist or a fellow, I would encourage you to apply to NIAAA for fellowships and for K awards, because we have them, and we don't get a lot of applications for them, and so I encourage you to apply. I try to bring this up as often as possible, and it's important. If you have a postdoc in your lab and they qualify for one of those awards, then please do give us a call. Find out what you can do. It expands your research and expands their experience in terms of applying for funding and getting it. Makes them more employable afterwards. And with that, I will stop. And can you take questions? Any questions for Gary? So have you programs in, when you go from LAPS to Get Well Again or LAPS to RELAPS, do you have programs analyzing that or studying this? Are you funding that sort of thing? Yes, I believe that they do study this exact type of thing, because that's important, to know just what is the frequency and what's the best way to, oftentimes it doesn't even become a blip on the radar screen because the addiction therapist may find out that, okay, I had a drink last week, and they just sort of check it down, but I'm not sure that they follow it as rigorously as you suggest. I have a question about workforce. So many fellows are interested in the nexus of hepatology and addiction medicine. And I think the question that I have is, would there be opportunities for NIAAA, perhaps NIDDK, to think about a particular phenotype of trainee that they would like to cultivate that has cross-training in addiction medicine and hepatology? Absolutely, there is. I think that we talked about this at the, when we met at the, when you came to campus, and I think that that's an absolutely important part. I think that there are some places that have had a part of their undergraduate medicine program where they incorporate addiction medicine, and they get some of that. But if I'm understanding you, you would like to think that a hepatology fellow might have a month of protected time to do nothing but addiction medicine or something like that? Right, so small fellowships are one start. My thought is actually, in our society, we have a pilot program to actually train hepatologists in transplant medicine, for example. So most people do an extra year of transplant, and there are several programs across the country that are piloting rolling that transplant year into the three-year GI and hepatology fellowship because that person already knows that they have an interest in transplant. I would envision the same type of thing for addiction medicine, where you actually have a training grant to study the, how to train a workforce who can have a fellowship that's actually perhaps two years of GI hepatology and one year of addiction medicine in that population. And that's probably gonna be a consortium of the societies, both the Addiction Medicine Society and ASLD, as well as the institutes to try to say, do we actually put out an RFA for a novel T32, for example, for people who wanna do research in these areas? So logistically, this is where I get stuck a little bit. Because you have a hepatology fellow who's got a family and a home, and he's in Pittsburgh, and Pittsburgh has a program, great. But if he happens to be in Cleveland and they don't have a program, does he then get a year to go to Pittsburgh to take the program, or do we have to establish one of these centers at every medical school, which is maybe a lot more expensive? Right, I think that. I think T32s lend themselves to that. Right, where we have T32s, yeah. And maybe we could identify those that are, because we have a lot more T32s in the psychosocial area than we do in the liver area. So I think that would be a good way of doing it. Great, I mean, I do think that both addiction medicine, specifically, also palliative medicine is another area where I think we need to train a workforce as well. So it would be interesting to figure out how to develop specific training grants to cross-train so we have a workforce that's able to handle it. That's interesting. I have a connection with the Nursing Institute. Maybe we could go that way, too. That'd be great. We have one question. Please come to the microphone, identify yourself. Great. Hi, Li Junming from New York. I'm getting very excited about this incorporated fellowship, adding one more year, or just this program. Can you do online, just to say online certificate, one-year training for alcohol, plus like the obesity, they have the obesity fellowship. Do they have that online? Physicians can take the course, get the extra certificate, and absorb patients more with this condition. I think the obesity medicine board process is actually quite fleshed out. I mean, it's online, you can sit for your boards, you can certify, et cetera. I think not for addiction medicine, at least not that I'm aware of. But I don't have the expertise to truly answer that question. I know that there are pieces of addiction medicine that are available online. So for example, you can do online courses in motivational interviewing, and that kind of thing, and have a certificate. So I'm not sure of anything that's actually well-established in the area. But again, I'm not an expert. This is certainly a question that I'll take back to the epidemiology and prevention treatment groups at NIAAA, and ask them what they think they can do with it. Yeah, good thoughts. Any other questions? Okay, so at this point, we'd like to invite all the speakers up to the table to talk a little bit about what are possibilities for collaboration across institutes, but also specific challenges that you face that perhaps most people applying for grants don't understand. Do you want to stand up and moderate, or do you want me to? You want me to go first, yeah. Happy to take the floor. So as you get settled, I think there's, so from the policy committee perspective, since that's the committee I sit on, and sort of this is a programming from that committee, I guess one of the things that we face in the federal government is this sort of in limbo being in adaptive mode every year when a budget may or may not be passed, and people are in continuing resolution, and pay lines are in jeopardy. So I'm just wondering first how you respond to policy changes and budget changes, and what you tell your investigators when we're in a situation like continuing resolution. Yeah, it's very difficult, and you have to play it by ear a little bit. We basically say, look what's happened in the past. We shouldn't reach our pay line that we had last year. Sometimes we have an interim lower pay line until the money is actually there, but NIDDK, we haven't come out with that decision yet. We're still waiting for the end of November. At end of November, I think. Yes, this one. So in NIAAA, we generally put out a minimalist budget in the month of November, which we've done just now, and it's probably, if you think about it, if on a normal year, if we were funded properly, which we were last year, we were funded ahead of time, we knew that in November exactly how much we had for the whole year, so they were able to put out a budget that was about 30% in November. We've probably put out a budget considerably lower than that this time, it's probably less than 20%, and it means let's fund those that are really high scores, everything else, and not too big a budget, and let's hold on to everything else, and it's gonna get funded later in the year, which causes a problem for grants management at the end of the year, but that's the way we deal with it. But you see, we're dealing with what we get is three rounds a year that we have to fund. We have a fixed budget, so we have to be careful with the first and second round that you don't overspend, because then the people that come into the third round are not gonna have enough money to fund to the same payline. So our grants management people are really quite good at predicting how much money to spend. So this 20% means instead of 30 or 33%, we always leave a little more money at the end of the year, and occasionally at the last minute, we can fund a grant that, when we finally get our budget done. And I'd also like to point out something else that all of our institutes have, or most of them, is an intramural program that's, for NIDDK is very strong in liver disease, but it's also strong in the NIAAA, they have excellent basic investigators. They also have an alcohol unit at the NIH that we collaborate with. NIAID has a laboratory, which was the premier laboratory of the world for many years when Bob Purcell was there, still very active. So there's also intramural that people can apply to, to come do fellowships, to learn how to do research, rather than to learn nuts and bolts of hepatology. We do a little of both. If I can address from the NCI standpoint, we have a similar guidelines with regards to the continuing resolution and the budget. The NCI will fund those grants that have the best scores initially. And basically, the individuals who have scores that may or may not be within the pay line are sort of held in limbo for a while until we do get a final budget. And one thing I also wanted to stress is that recently the NCI acting director, which was Dr. Doug Lowy, gave a presentation at the Board of Scientific Advisors, which was an open session, and he had indicated that the NCI has received each year more and more applications for grants. So the NCI has a limited budget, even though it increases year by year. But you have to remember, in addition to funding the grants that score well in this round, they have out years for grants that were funded the previous year and the year before. So when you get funded, you're funded for five years. And the institute needs to basically put aside a certain amount of funds for those ongoing grants in addition to those new grants. So this is sort of like a balancing act that we have to do. And it's challenging. So this is, the grants are funded for five years, so we only have 20% of our budget to spend on the grants that are coming in. The rest is what we call non-competing base. Now, often we can get the non-competing base down to 70%. But that means if they wanted to cut us by 20%, we would have no money to fund grants that year. And that's the difficulty with five-year commitments. And that's why we often will take a year off to try to get out from underneath this terrible non-competing base. Yeah. It's also the conundrum we face when we get an increase over a period of time, which we did during the Obama years, and then, or not even the Obama years, in the Bush years. And then it suddenly stops, and we end up with a kind of a lull in there that really hurt us. We were really short of money for a few years. Right. That special money that we got under Obama, in a way, was a little painful because then we had a higher non-competing base. Also, say the NCI has intramural program that's very strong as well. In fact, one of the heroes of NASH is Dr. David Kleiner, who's NCI physician, and helps with us with our, so this is the way we collaborate in many ways. Tom O'Brien does a lot of our genetics, who's NCI. That's a wonderful segue. My question is, what new initiatives do you have coming out which are all institute-based, from NIDDK to NIAAA to NCI? Could you tell us about some of them? Are you all participating in something on NASH, or are you considering that? If you could. Well, we don't have a budget, so it's very difficult. We planned some things, but we haven't gotten permission yet. There's also the Office of the Director that has broad-based RFAs, and they have a lot of money. For instance, what's called the Common Fund, which I call very uncommon to get that money, but the Common Fund is for a common problem across institutes, and we're now working with NIAAA to try to put in a Common Fund concept that would be partially applicable to NASH, partially applicable to alcohol. Do you have any examples of Common Fund projects that have crossed institutes and other big domains? The reason I ask is because nowadays, most good science is team science, and to amass a group of people to, for example, put in a spore or study things that are sort of cross-cutting disciplines takes a lot of effort, and yet, if we're working in, for example, big universities that have big centers and cores, it would be wonderful to see an announcement that actually is some sort of a Common Fund. We're looking for this phenotype across disciplines to study X. There was a Common Fund initiative that came out dealing with glycoscience, basically glycomics, and that was with NCI, along with, I think, General Medical Sciences, but the idea behind that was to develop resources that could be used for the glycoscience field that could be applied across all the different disease types as well as the different institutes. I could see glycoscience antigens being involved in vaccines with NIAID. I could see also, we're looking from the standpoint of glycobiology as potential biomarkers for early detection of liver cancer, so there are some Common Fund initiatives that are out there that could go across the various institutes and affect the collaboration among them. They're usually very basic. Yeah, right. Microbiome, metabolomics, metabolomics, and so they cross all the institutes. Got three quick questions. Yes. Okay, good morning. I'd like to introduce myself. I'm from Brazil. I'm an infectious disease physician, and I would like to know if we are eligible for any of those grants. Personally, I'm involved with HIV, HCV-co-infected patients, a great cohort of patients, and interested in epitocosinoma development in MeSH. That's the question. There is a provocative question from NCI that deals with HIV malignancies, malignancies associated with HIV and co-infection, so that's a possibility to apply for that. Okay, yeah, I actually have up here as well some flyers that list some of the initiatives, and that one is included in there, the HIV provocative question. Hi, thank you all for coming together and help us with potential research. I'm from, I'm Simona Jacob from New Haven. I also work at the VA in West Haven, and a common problem that we have, and so it's a question for the Common Fund, is many veterans have dual etiology, fatty liver disease, alcohol, and metabolic syndrome. Do you have any projects in mind to address this problem? So the question was, she practices in a VA where they have a lot of dual or triple diagnoses, things like fatty liver disease, alcohol, Pepsi, et cetera. So do you have any projects that actually look at multiple liver comorbidities? That's the question, right? More or less? Oh, not so much. HIV funding is tightly controlled at the NIH. Each institute has a goal. We're supposed to spend a certain amount of money, for instance, on HIV, and we are always actually searching for things to fund. And then we have to clear them with this panel that says it's HIV positive, but we've been quite successful in getting HIV money for dual infection, hepatitis B. In our hepatitis B network, we have a separate group that works with us, same protocols with HIV. And similarly, in NASH, we plan to add a HIV component to our NASH network. So in that way, we try to get these HIV goals. Goals that we're asking. My question was not really related to HIV, more the combination of NASH and alcohol. Although you cannot really define NASH, so alcohol and metabolic syndrome. Are you looking for treatment support, or are you looking for basic science in terms of the etiology of the disease? Treatment support. I'm more a clinician. Yeah, we have, I don't think we have any money for treatment support that I can think of. They usually have to be in some form of a question, a clinical question that's being asked, rather than just straight treatment. Under treatment, I think SAMHSA and a few other places have money for it. Yeah. But for example, say the question was, I am not sure how many of my patients with metabolic syndrome actually drink. I suspect it's much more than I have on paper. I would like to study the effects of alcohol treatment on a metabolic profile to see if actually alcohol is the principal driver. So I'm gonna have two groups of people. One who have alcohol treatment, and they have a BMI of X, and they have abnormal LFTs. And one who has a BMI of X, abnormal LFTs, and gets no therapy at all. And I wanna look at their AST, ALT, their weight after treatment, their general well-being, that kind of thing. We would support that kind of thing. Okay. And NIDDK and NIA had a joint meeting just this September on this very issue, the interaction overlap of NASH and ASH. And it is an unstudied. Yeah. Because they tend to say, oh, I want a real alcoholic. And we tend to say, we want a non-alcoholic. Exactly. And in between, of course, is a very important real, as we say, real-world problem. And so we're aware of that, and we hope to go forward with some ideas. And one of the initiatives that we put out in the last four or five years has been the development of a transdermal alcohol sensor, which basically you wear on a wristwatch. And we've had a dozen different prototypes out there, and they're a lot less obtrusive than the things that you see Lindsay Lohan wearing with the big ankle bracelet that looks like it would halt her from running very fast. And that's the sort of thing that fits into this type of a paradigm where you wanna know, are they drinking, how much are they drinking? So what I'd like is a dog actually in the clinic that would detect alcohol on the patient and bark. Oh, that would be good, don't you think? Right, I think they're working on those for cancer, so. They have a sensor going, and it's better than ours. Right, please, your question? Hi, my name's Archita Desai, I'm at Indiana University. I'd like to go back to the continuing resolution and sort of budgetary issues. So I submitted a K23 in February that was scored at a 30, and over the summer, as the budget hasn't been passed, I was sort of advised to resubmit. But I wonder, as you're talking about holding on to grants that at the end of the year you might consider funding, how do you advise someone like me to work with the program officer and the NIDDK to advocate for my grant, even though I will resubmit? I'm sorry, I can't hear you. So the question was about how to advise her in terms of resubmission of a K23. She got a 30, I assume it went to NIDDK? It was to NIDDK, yeah. I don't know where their payline is. That's probably a little above our payline, even, and we're pretty generous. Priority score, 30. Priority score, yeah. So I can understand why that would not have gotten funded. I would advise you to work with your program officer to resubmit, address the questions very clearly. I always tell people, hit the reviewers over the head with it, just make them understand that this is the answer to this question. And don't mince words, just answer the questions that they asked that are holding your score in that unfundable region. I wouldn't worry about the budget. The budget will come, and my guess, it's just a guess, but my guess is it's gonna be close to last year's budget, and that means that they'll still have K23s, and yours will be in that line. Okay. David Sloslowski is here at the meeting. If you can run him down. Oh, I didn't know that. We have a poster up front, yes. Okay, yeah, I will. If there's no one else, I have another question. Some of my research is in implementation science where NIDDK doesn't really have a program focusing on that, but NCI does, and I wonder if there are collaborations that are planned or could be considered for implementation science work in liver disease. Sort of healthcare delivery redesign, which I know is present in NCI. Yeah. So the question was about implementation science and health delivery, which NIDDK doesn't really have announcements for. So the question is, is NIDDK looking at that sort of implementation of healthcare delivery innovations in liver disease? Well, we have very few RFAs, and now very few PAs. We just, we can't do it. Our pay line is such that we can't manipulate it further, so that's the difficulty. Part of it is review, right? If you get a good score, if you're in the pay line, we pay it. But as far as giving preference to one thing, Nash versus the other, that's very hard for us to do. Now, Raj Koshy was saying they just pay by the numbers. We pay by the numbers, but our institute keeps aside about 5% of our money, so at the end of the year, we can fund special, what we call special emphasis, grants that didn't make the pay line, but should have, or there's a problem, the investigator's running out of money, it's a high-program area, we don't have enough in. So we do keep some aside at the end of the year, and we fund them madly in August and September. So we don't generally go out with announcements like that. I see. Anymore. And how do you recommend advocating for those kinds of special programs within NIDDK, knowing that NCI values that research, but it hasn't translated over to NIDDK? Well, NCI has, as Jay mentioned, we have a similar mechanism, similar approach in that at the end of the fiscal year, we do have some funds set aside for what we call exceptions. So these are grants that are either close to the pay line, but just a little above what the pay line is, or they are of high programmatic importance. So we would then advocate as program staff for those grants, and hopefully they would get funded. But, you know, everyone has their own area of interest that they are focusing in on. And the institutes, I know the NCI doesn't have all the different types of funding announcements that are specific for your area of research. So the idea is to look and see within the NIH grants what is more in line with what your interests are. And if it isn't there, there's always the investigator-initiated R01 grants. Okay, thank you. Because there's a lot of research out there. So I think we've reached the end of our allotted time. I wanted to thank everyone for coming to speak to represent your institute. I want to thank my co-chair, Lopa Mishra, without whom this wouldn't have been possible, as well as the Public Policy Committee. Thank you all for your attention today. Thank you.

NIDDK

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NCI

liver disease

alcohol research

funding initiatives

collaboration opportunities

implementation science