 Okay, so we have the lights up, we're videotaping this, so we need to make sure people go to the microphones so that we can hear the questions, and I'm just going to sort of be the referee here. So we'll start with Max over here. I'm Maximumke from NHGI, so these are two fascinating talks, and just the thought that you can diagnose those people easily who might have an easier time quitting, I think that's just fantastic. And then to think there's a new medication out there that may be helpful for them to quit, I find just fantastic. So I have two questions. One is, actually I have my wrong piece of paper here, one is the one on side effects of current medications that help people quit smoking. And to me, I'm a firm believer in P-values, I'm a firm believer in whatever is scientific, I find it striking how I was touched by the fact that an acquaintance, not a friend, but that an acquaintance of mine was on Chantix and was close to committing suicide. Clearly he didn't succeed, but I was struck that that is one of the side effects of Chantix. So that's one question, are the other side effects of either Chantix, or Butron, and others. And then the other question is, and this is not part of your research, but maybe just for my own benefit, what is being done in finding out who's susceptible to starting smoking in the first place. Not that I want to put that on the newborn screen so that people would know this from the get go, but I would find, I would love to hear more about that, so thank you very much. Sure. I can start with this. So with respect to the side effect issue, that's a really important point, I'm glad you brought that up. So I mentioned both bupropion and verenicline have black box warnings, and what that means is that there are rare, based on current data, less than one in a thousand, or maybe less than one in two thousand, significant neuropsychiatric effects in terms of increased aggression, if it's turned inward, increased suicidality, or turned outward, and you know what, it's hard to tease apart the actual empirical data from what's in the press, because these are very salient events that get played up in the press. The actual data, in fact, there was another study that came out from England, that in a study of close to thousands of people, they did not see any of those. So we're very interested, as other scientists are, in trying to identify who is susceptible to these neuropsychiatric effects to be able to, in the targeted therapy in personalized medicine, to not prescribe these medications for individuals who may be susceptible. It's particularly challenging when it occurs in one in a thousand or five thousand subjects. So I think to do that, what needs to be done, I think there is a phase four large study that Pfizer and GSK and others are getting together to do to track a sort of post-market study and where they might have DNA to track thousands of people to both understand the incidence of these effects and perhaps try to be able to understand who's most susceptible. So these are real, they're rare in our study. We actually saw a couple of instances of suicidal ideation, but they were not on active medication because we did an unblinding. Nicotine withdrawal in the presence of a psychiatric history can also prompt people to act out in certain ways, so it's very hard to really understand these. I will say there are other side effects that are concerning and more common, like abnormal dreams and sleep difficulties that are due to the cholinergic effects of these medications. These may occur as commonly in 20% of people. Here we have a chance of using pharmacogenomics to really understand that and to target therapy, and that's something we'll be doing in our study. With respect to the genetics of who becomes addicted, the slower metabolizers of nicotine by CYB2A6 genotype or by the NMR, there's evidence that they are less likely to initiate smoking. Of course, to understand the genetics of acquisition, somebody needs to actually be exposed to it, so you look if somebody's exposed to it, are they likely to kind of progress to regular use. Slower metabolizers are less likely to move to regular or dependent use, probably because they're more prone to get toxic effects of high nicotine levels. There's some evidence with some of these chromosome, the alpha-3, alpha-5 subunit gene that may play a role in who transitions to regular use in smoking. The issue is that these effects in acquisition of smoking are really, really small. We're talking about one to two percent of the variance because of the importance of environmental factors and gene environment interactions, so it raises the question of what would you even do with this, because you want to do your anti-smoking PSAs for the whole population. You want to do your anti-smoking interventions in all of the schools, so I personally haven't figured out how to apply data on acquisition of a behavior when there's so much noise in the estimates, although I'm thinking that PSAs where God comes down and delivers medications may actually be a strategy we should consider. We actually had one of our focus group participants say, you know, Jesus wants you to quit at the billboard. Yeah, but anyway, but thank you for those questions. Actually, Max stole my question about the susceptibility and whether there was any indication about that. So I'll do my second question to Alexandra, which is a question about the, I guess, the fact that most smokers, it's amazing, don't consider that actually tobacco is a drug and that, and so how is it that they balance this consideration that they wouldn't take a medication to help them quit smoking, but in fact they're using a drug and did you talk at all about that in the groups? Well, it's very interesting that the perception of smoking is much more a behavior than a drug in the average consumer's mind. I smoke because I'm stressed. I smoke because my mother smoked. Everyone in my family smokes, but it's really understood as a behavior. It's not understood as taking nicotine into the body. And so there's this other side when it comes to taking medication. Some people who do acknowledge that nicotine is a drug that they're basically taking in, they will say, I don't want to replace one addiction for another. So there's a lot of suspicion about medications. And I didn't get into it, but there's, in the black community, there is a lot of, there's a heightened level of scrutiny and kind of a hermeneutics of suspicion, if you will, about doctors prescribing medications to black patients, especially new experimental medications, and there's a distrust of taking medication. So I think that there's, I think there is a disconnect there, but one that we, as public health researchers, need to understand and use to our benefit in designing more effective interventions. I guess then the follow-up to that would be sort of the question from Max about susceptibility and using genetic information in these target groups to talk about susceptibility to uptake of smoking. Would that be an area, again, where genetics would be helpful, perhaps? So we did not include questions on that in our national survey, but we did explore those questions in these multiple qualitative research activities that, where we did capture responses of upwards of 300 black and white smokers that are all less than a college education. And I think that it's just, that is not a green light on that one. It really smacks, trying to lead that, trying to express that with those folks in a culturally competent way was very difficult. And anything that you're trying to tell us that we're defective was really the, I mean, that is just dead in the water. I wouldn't even go there. Not in the context of lower SES populations. I think that that might work with more affluent and highly educated. Might work in school contexts like Janet's work. I wanted to add about the God's will and medications and people being opposed to medications. And I think this is something that the substance abuse community has experienced for a long time in the form of things like AA. And the AA and other types of models like that, which do emphasize and have their own efficacy, but in terms of God's will. But it's been posed as a barrier to translation of substance abuse treatments to practice because of those philosophies. And I don't know if there's anybody here who does research in other areas of substance abuse, but I wonder how, I know that those groups are trying very hard to kind of tackle those beliefs which interfere with all types of treatments. So a couple of questions. First, for Karen, I'm struggling to understand addiction. From your introduction, the feel good part of nicotine is the release of dopamine. But I don't study smoking cessation, but we all know people that have stopped smoking. They put the cigarettes down, they walk away, they say, what's the big deal? And then others who repeatedly try over and over and over again. So that somehow seems, to me, incompatible with this idea of a fast or slow metabolizer. What else is going on in this picture? So, well, you've given the perfect premise for the fact that there's individual genetic differences in people that help some of them to be able to put down their cigarettes and quit. I'll use myself as an example. I was a chipper for a long time, have one on the way to work and one on the way home, and I could go away and not have any. But so there's different genetics. And I'm glad that you brought this up because I was focusing on nicotine metabolism and drug metabolizing enzymes, genetics as a way of explaining that variability. But nicotine addiction is so complex, nicotine effects not only dopamine, but multiple neurotransmitter pathways and opioid peptides. And that's why any of the measures that we have are accounting for a small proportion of the variants, because after all, we're talking about the brain and we have multiple SNPs within pathways and multiple pathways and interactions with environment. And the challenge of fully characterizing this from the biological level is related to this complexity, which would require studies of the size of hundreds of thousands of people to be able to look at the complex genetic architecture to explain it. So you're right, it's extremely complex. Some people who may be social smokers who don't have the genetic factors that produce brain alterations that make it difficult to quit, Ken gives their cigarettes up. Other people we've seen come through who have all the motivation and will in the world and just can't do it. And so I think that's genetics, it's environment. And as far as what's happening in the brain, it's not just the stimulation of dopamine. We know that chronic smoking produces upregulation of nicotinic receptors throughout the brain. So when you have abrupt cessation, then you have all of these youngbound nicotinic receptors. And that's been associated in pet studies with the types of craving and mood symptoms that people face. Some people can tolerate that distress more than others, which probably has to do with their environment as well as their genetics. So many, many different things are contributing to that variability. Not everyone is addicted though. And then for Alexandra, you talked about engaging religiosity here. What are you thinking about here? Public health through churches? Or what are your ideas there? I'm actually thinking of something different. I mean, there's been a lot of work in the public health community of using churches as a site of recruitment or delivery of cancer screening programs and so forth. But I think we really need to develop interventions that are working with the thought models that are operative among these smokers. So for example, I mean, I said it kind of an offhand half facetiously, but the smokers that I was talking to in the black community, they were saying, really? I mean, if I'm driving down the street and I see, I mean, they talked about billboards. They talked about, I think, developing an intervention that mobilizes. It's basically there are, in theology, there are schools of thought that actually address this in liberation theology, for example, which is really taking the needs of the oppressed. It came out of Latin America. And mobilizing that to say, basically, God wants you to have the fulfillment of your humanity in the here and now, not in some afterlife. And what is it that is getting in the way of you realizing your full potential as a human being? And so some of those things in terms of the, I loved the gentleman who talked about God makes everything that's good, and God gave us the medication. God gave us this new treatment that can help us be around here for our grandchildren. So I think mobilizing those kinds of messages. And I think we need to do a lot more scientific work to identify what messaging will actually be effective. But I think it can be done. And I think that there's something very consistent and persistent here in terms of the plaque community. Over here. Great. Thank you both for your fascinating talks. So when thinking about translating these genomic advances, I'm really interested in patient responses to the information and communicating that information. And so Karen, your work demonstrates that even with these pharmacogenomically matched or tailored treatments, there's still going to be a proportion of patients who don't successfully quit. And I think when we're concerned about issues about how people will respond to this information, if it will inspire distrust because this tailored treatment still isn't effective, I guess I've wondered whether you have all thought about that, how you've thought about ways to communicate and market these tests to consumers so that they have sort of realistic and appropriate expectations, yet are still enthusiastic and motivated about trying this new strategy. That's a very important point. We did a study many years ago. And this was before treatments like nicotine patch were even available where we tested the effects of communicating either results from genetic testing for lung cancer susceptibility to a CO test about their exposure to a control test. And what we found in that study from 1993 was that smokers, given the genetic information, they tried to quit more often. They didn't have the pharmaceutical aids that we now have. But it also made them more discouraged and depressed because they weren't able to quit and then it could lead to more futility. Fortunately now, it's not just genetic information without an action plan, it's genetic information with an action plan. But as you say, despite that, you'll still have people who are unable to quit. And I think that having the right messages in terms of, so that you're not undermining somebody's confidence and having the right counseling education to go along with it will be really critical. Yeah, I would add that I think that not setting expectations too high, having realistic expectations in the communications, people love learning information about themselves. You just go on to ancestry.com and you can see there's this voracious appetite for anything about my personal status. And so I think that people feel, in my research, I've found that people actually feel affirmed and respected that somebody is paying attention to how they might be different than another smoker. Having said that, I think it's also important to say, this is something that we think will give you a better chance of being able to quit this time. And that's an honest statement. It won't necessarily make you quit, but we think it will really give you a boost. And I think patients are sophisticated enough to be able to understand that. Great, thank you. Hi, both of you, it's great to see you. You too. This is Joy Boyer, LC program. My questions have sort of been answered, but I'm gonna ask slightly different ones now. The first question is, as far as medications go and the distrust of medications, is the distrust of medications for nicotine withdrawal or heroin withdrawal or something like that, is that distrust different from the distrust they might have for a statin or some other medication? And is that different something that you can work with as far as helping them? Yeah, we did not have the data to answer that question. I think that there is definitely, as you saw, there's consistency in views about medication across substances. But what we haven't done yet, and that's actually an interesting thing to know, is whether there's consistency also in terms of addiction-related substances versus medications in other clinical contexts. There's been a lot of work done on pain medications. Some of it is on the consumer side, much of it is on the provider side of under-medicating minority patients in pain and so forth. But I think that's an important area of future work because I think depending on that answer, some of what we're finding out, particularly for disparities that affect the black community may be applicable to many other kinds of other conditions. I think that's a great point. One of the findings that's out there relevant to that, which in the genetics areas that willingness to undergo genetic testing or to have samples that are banked to use for different things is much greater for something like statins or cancer than for something that's stigmatizing. So maybe in the same way, the stigma associated with addiction or mental health conditions might also make people more susceptible to not wanting to use the medications, but it's a good hypothesis. Yeah, and my impression is though that with these many focus groups and individual interviews that we've done over the past few years, that that effect in terms of your hypothesis is really swamped by this other effect among the majority of African-Americans who understand themselves very religious or spiritual, that medications is somehow a failure of faith. And that is the link that we're discovering. Yeah, it does seem like the use of faith could be a very interesting and productive avenue. Yeah, it's reframing medication as something that is consonant with being a person of faith, not intention with that, right? We're starting to get so many people in the aisle, the fire marshal's gonna get mad at us. So I think Bob was next, and then we'll clear out this aisle and move over to this side. Yeah, I just had a question about more of a dissemination implementation question. So given the fact that a lot of the trials in the US and Europe have incorporated a significant clinical cessation counseling component, and for low SES populations, we're relying as a public health strategy on quit lines. That's kind of the main modality for counseling. What are your thoughts about translating kind of the next generation treatment and pharmacotherapies tailored to individual in a context, primary care context, like in the HRSA clinics, you referred to where most of the interaction we're gonna rely on is quit line based as opposed to in person clinical cessation counseling. So one thing that could make a big difference, I realize we don't have the resources to have people in a community health center in these practices and we will need to rely on that. But I think that one thing that might make a tremendous difference is having the quit lines match to the smoker subpopulation. So that you could have quit line workers who are calling, you could either do it by zip codes, you could do it by patient lists or whatever, but matching the quit line counselors to somebody that the smoker from their social context can relate to, I think would make a tremendous difference and that's an empirical test that we could do. I think you could also incorporate testing, you could send out a kit for getting saliva to do and a test for treatment tailoring and do it in the context of a quit line counseling program as well. Karen. Thank you for two great talks and they were so well integrated. So it's generated a few questions, an integration question. Karen's data you had looked mostly European and then Alexander's focus was mostly in the African-American community. So I was wondering about communicating the lack of data and the impact, if anything, you might think that might have on uptake. That was my first question and my second question is I think a relatively simple one but maybe it actually is complicated and that's the unintended consequences of pushing medication and what impact that might have in people thinking, well I'll smoke if, you know, I know there's a lot of probably behavioral and social science research in that area, so those are my two. Okay, so we actually, in our studies of the NMR, we had probably at least a couple hundred, maybe 300 African-Americans in those studies. So those were European ancestry and African ancestry range from 10% to I think it was 30% in the trials. And so we were actually able to look at differences by race both in the efficacy of the use of NMR and so forth and did not find differences there. However, we did find that African-Americans tend to be slower metabolizers, so there's some things. So we were studying both groups but I'll let Alexandra respond to that. And I can say that one of the things that has really facilitated my research is the fact that Karen has validated the NMR in African-American patients. And so in the 300 or so smokers and physicians or now maybe 400 smokers and physicians that I've talked to about this in interviews and focus groups as well as in our national survey to be able to say that this has been validated in African-Americans has made all the difference in the world I think and I wish more researchers would follow Karen's suit and make that effort because I think that it's good to do scientifically but it also has tremendous implications for communications and translation. Right. Alexandra, I enjoyed your talk. So I wanna push on this question on intervention. Have you thought about the issue of really engaging and qualitative research actually the spiritual community leaders, seminaries to kind of explore this concept that the individuals that you had in your study were presenting? Yeah, so what I see going forward in terms of this very powerful pilot work that we have is that I'm not particularly interested in engaging with black churches as a site of recruitment or whatever but really engaging with black religious leaders in this issue. There are some very powerful pastors of black churches in Boston for example. And they have a history of acting collectively in public health campaigns and so forth and I think that varies from city to city and state to state. But I think that what's needed at this point is to develop the effective intervention and communication that should happen. I think that you need the engagement of black religious leaders because if you get one bit of as you know, you get one bit of the nomenclature or the slang or anything wrong and you are dead in the water. So it really has to feel organic and that reflects respect for the culture. So I think that that's the way that we should go in the future. I think both bringing in the spiritual leaders as well as healthcare providers would be an interesting way to explore the world. Thank you. Hi, thank you. Do you have any data on the success rate of quitting for those different categories of influence of God's help versus medication? We don't actually. That will be our next hour one. Actually, while we're on that time, the one question I want to sneak in here. I thought that, I mean, those data I thought were very interesting but you looked at African Americans. If you look at other groups, has anybody looked at other groups and seen what those distributions look like? No, this is the first work in this area and we actually had to reduce, we had to stick with two groups for comparisons purely for budgetary reasons in order to do it well. So we thought it was, you know, we went with African Americans because that's where the most dramatic disparities are in smoking related illnesses. So we prioritized them, but we had wanted to do this also looking at Latino populations in Asian. So if you would like to give us money to do that, we'd be happy to do that. How much do you need? I don't know what happened to my wallet, but okay. You asked for that one. You asked for Hannah. I feel like I'm sort of pushing the same issue that everybody else has had with you, Alexandra, but I think this is just fascinating. And I don't know enough about this and I'm hoping your theology background you do, which is it's so appealing, this idea that I find it very appealing that God gave you your body to take care of you. God gave us the brains to make medicines, you know, and to be a good steward and to take care of your body would take these medications. But I wonder since you have these two pretty distinct groups, if that is theologically, you know, would this be a hard movement for people? If you believe differently than that, is that a huge barrier in terms of messaging? Well, going back to Vince's comment, I think this is where the partnering with the community-based religious leaders is critical because how people make that shift, they're not gonna be listening to me about that shift. The reframing, you know, we need to talk with the smokers themselves to figure out what reframing would actually resonate with them. And then we definitely need the help of people in the community, not only the religious leaders, but the people who are at their local community health center that are from their neighborhood. We really need help in delivering that message. It has to be a message that comes from the community. And in that framework, for example, the oppressor in that theological framework would be the tobacco companies. And the data that might be relevant as part of that communication might be the over-targeting, the oversaturation of black communities, of smoking ads and so forth, and, you know, free packs, selling singles at the corner store. So I think that there's a lot that can be done in that, but I do have hope that with the right, I mean, even the movement I saw during the discussions with these focus groups and 101 interviews, we saw kind of a light. I think it's possible. Yeah, because I guess that's my fundamental question, is even with the spiritual leaders, will their faith-based ideology incorporate, will they be open to a reframe? I guess that's my question. If it comes from their spiritual leaders and community folks that they trust, I believe the answer is yes. Okay. So Karen, my question for you was, do you imagine a time in the future where we're doing these specifically targeted medical interventions? And let's say it's even further advanced from where you have it. Do you imagine a day where the counseling will have such a small added effect to be not so important? Will this just be a pharmaceutical intervention? Well, I think that counseling, at least even minimal counseling is always important because it's not just a biological addiction, it's a habit. Now, the biology of nicotine, hijacking these circuits in your brain is what creates that habit cycle. But in order to break the habit, you need to use strategies and stimulus control and change things in your environment. So I think that some counseling to prepare people to quit and some booster counseling will always be needed. But I think that it could be get to a place where it's very self-help, telephone-oriented, and minimal to make it more accessible to a broader population. That actually makes me think in terms of your prior question, Barbara, that, for example, all the great, I just gave you a couple, but they were just fantastic stories about meeting God halfway. And those other kinds of avoiding bars or other places that are triggers for you in terms of smoking, all those other things come under the category of meeting God halfway. You can pray about it, but you need to meet God halfway. So it's not just the medications. And I think that any kind of intervention should really deal with the full range of factors that we know affect smoking. And that's part of the general guidelines is for behavioral and pharmacotherapy, pharmacotherapy first line with some behavioral counseling. So I think it will always be that way. We can find easier ways to disseminate it. And interestingly, the fact that the NMR would just be spit test or a cheek swab or whatever, I think that that also lowers the bar because they're used to getting a swab to see if they have a strep throat. It somehow puts it out of the category of going giving your blood for DNA. It somehow is really helpful. Bar up, all you have the microphone. I know you have a brief. Yeah, so I just wanted to extend an invitation to everybody who is here and anyone who you know might be interested. We're having a reception to initiate the start off of SBRB celebration of its 10th anniversary, which will culminate October 30th. So stay tuned. Tonight at 5.30 at less of my house in Bethesda. So any of you are welcome to stop by on your way home and I have my address on a sheet of paper here for anybody who wants it. So welcome. Okay, and with that, let me give a big thanks to our two speakers who absolutely hit home run batting cleanup. As I say, this was a fantastic session. I also think the audience, this was a great discussion. So with that, have a good rest of the day everyone. Thank you.