Chapters Transcript Video How advanced clinical research evolves into patient access When I talk to a patient about the clinical trial. if it's a randomized trial, I say the worst that will happen to you is you get the best treatment I would give you without the trial. However, you're on a clinical trial, so you get special attention. You have a coordinator assigned to you, scheduling your scans is gonna be eas easier. Scheduling your clinic visit will be easier. If you have a problem with side effects, there's actually somebody you can directly call. So you actually get better care on a clinical trial. Then you would get a standard of care. Hi, I'm Lindsay Carrillo, director of Business Development at UCI Health. Hi, I'm Doctor Sunil Verma, Associate Chief Medical Officer of Ambulatory and a laryngologist here at UCI Health. Welcome to Physician Huddle by UCI Health. Today we're joined by Doctor Farshe Dayani, medical director of the Stern Center for Clinical Trials and Research and Associate Director for Translational Science for the Chow Family Comprehensive Cancer Center. Welcome, Doctor Dayani. Thank you. So take us a little bit through your journey. How did you come to UCI and tell us a little bit about how your career has evolved since you've joined us. Time flies, it's almost 10 years now, I just realized, but um. Uh Before I came to UCI, I actually, uh, chose a stint to go to, uh, industry, and I was in Switzerland working on uh, oncology biomarkers at Roche Diagnostics for about 11 year and a half, but very early on I realized that I missed patient care and the purpose of, you know, training to become a physician and oncologist. So, uh, around that time, one of my mentors during fellowship, Doctor Susan O'Brien, she had moved to UC Irvine as the medical director of the clinical trials unit. And it happens that we have family here in Southern California, so we came for a wedding. And I reached out to her and said, oh, he says, why, why don't you come for an interview? So that's how it all started, but um, Uh, in all seriousness, I think where we were with Doctor Van Etten and Doctor O'Brien joining in 2014, 202015, there was a, uh, a change in the, at the cancer center with an emphasis to, uh, grow the clinical trial, uh, portfolio, and I think the specific task for me coming on as faculty was to expand on the, uh, GI portfolio. I think there was a room for growth. We had a Uh, the patients and we had a special patient population given our demographics and location, and I think the idea was to expand on that and it took a while, it took, it took a while, it took about 400 business cards. Back then, we would still see um Medical science liaisons and reps in, in the office and I knocked on every single door. I said, we are here, we're under new management and reopened for business. But then uh uh we were fortunate enough, uh, in 2017, we were chosen for two of the pivotal trials in, in liver cancer, HCC that changed the standard of care. And due to our population, we were able to contribute well and once that Uh, those two trials sort of, uh, accrued, we, we got our name out and then I think from there, we've been able to significantly increase our portfolio and, uh, uh, our footprint here in, uh, Orange County in Southern California in terms of offering the best trials to our patients. And I think the second part of it was starting to write our own trials, what we call investigator initiated trials. And that also sort of went hand in hand with working with, with sponsors and convincing them that we have ideas where we have the patients that we can uh bring these trials to and that sort of was the second column that we tried to expand. So, um, over the years, uh, getting involved more and more with clinical research and experience and uh uh increasing our portfolio. So by the time Doctor O'Brien uh retired from her position, Uh, Doctor Van Etten reached out and asked if I would be able to step in or willing, and obviously, I always, uh, it was a dream job and, and I think UCI gave me a lot of support to grow and learn and, and, and, uh, I don't think I would have, we would have been here where we are today if I hadn't been at UCI. I think it's a very special uh environment in terms of uh collegiality and, and support by colleagues and having the opportunity to create. So, you're talking about, so at the beginning, I guess you're saying this was more about participating in bigger trials and then the second phase of the development was essentially designing and executing your own the team's desires for what they wanted to test and execute here. Exactly. I think the low hanging fruit is what we call uh uh industry sponsored trials where we approached, they want to develop a drug and they need sites and we have to be selected and contribute to those. Uh, and to be honest, uh, those trials pay the bills. You know, we need, we need a healthy portfolio and mix and match of industry-sponsored trials. But then, uh, as an NCI designated cancer center, as a matter of fact, the only NCI designated cancer center in Orange County, uh, we also have an obligation to participate in cooperative group trials. And the third column is these investigate, initiate trials, and those are the highest regarded by the NCI as well. And I think for us as clinical researchers, you know, I spent half of my life in the lab before I, uh uh uh before I graduated uh fellowship and became attending and moved to the clinical research realm. And for, for us as clinical researchers, I think getting a Nature paper is Coming up with your own idea, finding somebody who can um fund it for you, writing a protocol, getting it through IRB all the uh hoops, opening it and rolling, and then ultimately being able to publish so the colleagues are aware of the results and then build upon that. So, uh, that was the second part and that takes obviously a while. Uh, but, um, that part, we've been very, very successful at UCI and I think we tripled our number of IITs over the past year. And that's very important because we're going into a renewal of our P30 grant in January. So before we get to some of the stuff that you're working on currently, just give us some perspective. Like, how are you balancing the patient care aspect, which obviously keeps you very busy and there's a lot of patients and a lot of needs there with also being a researcher. There's a lot to keep track of, a lot of paperwork. Um, do you just like kind of weave them in together, but, or how are you balancing those? That's an excellent question because, uh, we are expanding, we are bringing on a lot of junior faculty and, uh. I always explained to them, uh, becoming a successful clinical researcher in academia, you have to sort of appreciate and respect the Maslow pyramid of clinical research, and the first one is, uh, see your patients, get your notes done, to your billing before you go home, because if you, if you don't get your work done by the time you leave clinic, then all that What we call protected research time is not protected anymore because you're still catching up. So that's the first part of it to, and, and part of it comes with experience, right? So, so you're comfortable taking care of patients, but The most important part of it, if you're a clinical researcher. Uh, protected time doesn't mean not seeing patients. You can't be protected from, from the people you're trying to help and the, and, and the subjects that are actually uh part of your career, right? So, I always say you need, you need to have patient exposure and at the end of the day, if you're the investigator for a protocol, you're your biggest advocate for that protocol cause um you, if you're not there and advocate for that trial and enroll on it, nobody else will. So you do need exposure to patients. You need to have clinic. That's the first part, but Um, as I said, you need to, uh, get comfortable, uh, take care of the patients, get your notes done, do the billing, close the encounters. These are, these are basics, and then basics, yeah, not here, not a given here, but let's be honest, that's the first part. But then the next, next step is, uh. And that's maybe where I trained at MD Anderson. Um, unless you cure everybody with no side effects, there's always room for improvement, and that means a clinical trial is always the best option for your patient. So I told, tell my junior faculty, always look for trials and enroll in other people's trials. That's sort of the second step in this hierarchy because people will start trusting you and seeing you as a colleague. And when you open your own trial, they will enroll on your trial as well. So you have to be scanning all the time, they do this? Yeah, and, and we have, I think, revamped the Stern Center and our clinical operations to help junior faculty to go screen their clinics, actually be physically present in clinics with coordinators and say, hey, this patient might be a, a candidate. But I think we've done a pretty, pretty good job of bringing on new faculty who are. Internally driven and motivated, the true, they truly want to be clinical investigators and I think that helps a lot with, with the success we've had in terms of increasing our um uh portfolio and accruals. How do patients find a trial? Is it something that a patient will look up on their own after receiving the news of the diagnosis, or is it more that their own oncologist will refer here? That's a very, very important question, and, uh, the, the ways to land at UCI are getting more and more. There are more roads to, to, to come to UCI. So obviously, uh biggest pool is our own patient, uh, population that we have or tumor boards. Uh, where we review every patient and, and see if we have an appropriate trial. Um, at the Stern Center, we have created, uh, uh, a website and maybe we can share that as well, uh, with, with flow charts. So any physician, any patient, If they go, if they Google UCI Cancer Center flow charts, it will take them to the website and it's very, very straightforward. You click on the disease site and then you can see, for example, gastric newly diagnosed and then you see the list of the uh trials and you can click on them and, and it takes you to the number. We also have a a clinical trial email uh. Uh, where, where we get a lot of inquiries from physicians, but also a lot of family members and patients saying, I'm interested in that trial. Um, there's a website called clinicalTrials.gov where every single clinical trial has to be registered with basic inclusion, exclusion criteria. And what we're finding is more and more patients are getting more savvy and they go to clinicaltrials.gov. They put in the region that they live, which is Orange County, for example, or Southern California, and then all the trials we're participating uh show up. So, all of the, and then we send out uh monthly newsletters to physicians um with trials that we highlight. We go out to the community, um, um, we, we present the work we're doing to, uh, community physicians. So there's many different ways we get our patients. And, and when you're doing a trial, are you, what do you, you're comparing an experimental arm to, to what are to standard of care, to placebo. I think a lot of fear of people going into a trial is I'm gonna receive substandard treatment or this really sort of uh experimental treatment and I'd rather just go with what's proven and right. So this is a very, very crucial point, um. The ethical principle that we go by and we have very rigorous disease-oriented team meetings where we vet trials before we even move ahead with them in terms of approving them. And this is one of the biggest uh hurdles initially is the scientific validity and, and the design of the trial. Meaning, when I talk to a patient about the clinical trial. if it's a randomized trial, I say the worst that will happen to you is you get the best treatment I would give you without the trial. However, you're on a clinical trial, so you get special attention. You have a coordinator assigned to you, scheduling your scans is gonna be eas easier. Scheduling your clinic visit will be easier. If you have a problem with side effects, there's actually somebody you can directly call. So you actually get better care on a clinical trial. Then you would get a standard of care. So that's sort of a guiding principle. A lot of our early phase trials or phase two trials don't have placebo, don't have randomization. Uh, we have a lot of those because they're not a huge number of exciting new drugs with novel targets are coming out. And the exciting part of those is, we already have enough preliminary data for activity. So we know these are actually better probably than what we have today, but the patients do not get randomized, so we know every single patient who goes on that trial will receive the experimental drug as well. Um, and that's sort of uh. One of the things that changed, I think the outcome for a lot of our patients having access to these uh novel drugs in an earlier setting. So one of the things we've talked about is uh liquid biopsy, and there's a lot going on and you are doing a lot in that area, but how do you see that sort of changing that standard of care because there's a lot of like milestones and different steps and scans and proof that, you know, the treatment is working, but you're telling me that this could change all of that. Hopefully it will change, and I think the, the landscape is changing. I think, um, by now. 1213 years into next generation sequencing becoming more uh standard and, and everybody's aware of that in oncology for tissue testing um to, in terms of looking for what we call driver mutations or new targets for novel therapies. Um, that's, I think pretty established, but then over the past Uh, maybe 67 years and now it's, uh, expanding uh more and more, uh, platforms that provide that service, uh, what we call liquid biopsy, meaning trying to use the patient's serum for, for, uh, uh, next gen sequencing and methylation scores. So, uh, principally, circulating tumor DNA or liquid biopsy can be used for, uh, decision making in terms of what drug to use and that was the traditional role. Um. Treatment monitoring, meaning is the treatment working or not? Um, I think one of the biggest game changers is uh molecular residual disease or microscopic residual disease monitoring, meaning a patient who had Presumably curative intent treatment with surgery and or radiation and chemotherapy and it's in remission. Historically, we just watched them up to 5 years, did scans and hope for the best, and by 5 years, they said you're cured. Now, trying to determine who is actually cured within 4 weeks of having the surgery versus who needs more treatment. So, this is MRD testing and that field is expanding a lot. The one field where we, I think we are ahead of our time in terms of enthusiasm. Is early detection. And the reason is if you look at At least in GI cancers. The staging is not by tumor size, it's by invasion. Meaning a tumor that's small but aggressive, as, as soon as it has access to blood and lymph vessels, if it wants to go, it will go. Um, so, cancers that are staged by invasion, depth of invasion, not by size. Are only prevented if the screening prevents pre-cancer. Colonoscopy does not improve survival by detecting early-stage cancer. It prevents, it, it improves survival by detecting high-risk adenomas that are resected that never become invasive. A prime example is pancreatic cancer. As a matter of fact, I was just I think I can say that. I was just asked by one of the uh major journals, clinical Cancer Research, uh, to review a, a paper from the Northeast looking at uh algorithm in the blood to uh detect pancreatic cancer early. Now, what we know is Every single pancreatic cancer patient needs chemotherapy. Why? Because it already metastasized at the time it becomes invasive. Otherwise, the guidelines would say, oh, if it's a small one, you watch it and every single pancreatic cancer patient per guidelines requires chemotherapy. So, I'm looking forward to reading that paper, but If the blood test only detects early-stage cancer, the, the cat's out of the back. So, we will always look and see what percent of high-risk IPMN, for example, are detected. And when you look at the, you know, there's a lot of buzz for colon cancer uh screening. When it comes to high-risk adenomas, they're like 13%. You don't screen to find cancer, you screen to find pre-cancer, so you prevent it from developing. If you have a CDH1 mutated stomach cancer, you don't screen them until you find stage 1 cancer. You remove the stomach before it gets. So that part somehow the community has embraced and, and is enthusiastic about because it sounds good. But then, the areas where we have so much better data and where we can change the outcomes, for example, decision making in the adjuvant setting based on MRD testing, there's still a lot of pushback and hesitancy, you know. Um, tell us a little bit about your role. You've referenced the Stern Center. So tell us a little bit about it and, and what do patients need to know and, and what do doctors need to know about it. So, the SEN Center is the clinical trial office or clinical trial unit uh uh of the Chow Comprehensive Cancer Center. So every single clinical trial uh within uh the Chow Cancer Center is managed by, within the SEN Center. Um. It's, it has grown from, I think, 20 FTEs when I joined 2016. We are at 160+ FTEs. It's a huge machinery and it's literally the village it takes to do good clinical research. And we pride ourselves and, and it's, it's a very matrix environment with clinical operations, uh, finance support, regulatory support, and highly qualified and trained. Uh, clinical research coordinators that interact with the patients, managers, we have succession planning, we have, uh, promotion planning. So part of the, uh, quality of the Stern Center is that the majority of our senior leadership in terms of cleanups, etc. within the cancer center comes from within, and they, they, they sort of come through our own farming. They come as assistant data coordinators. They really learn everything from, from, from bottom up. So by the time they're ready. And I always tell my investigators and colleagues. These people are trying to help you and and protect you actually from making mistakes because mistakes can be costly for the patient and, and for the FDA and for the institution per se. So I think what we have is a very, very high-quality clinical trial unit with highly qualified, uh, dedicated staff that's growing by the day because uh our, our portfolio is growing. And I think that's one of the best uh units I've worked at in, in, in my career. That's really impressive. Tell us a little bit like this pressure to publish or to present at conferences. I know you're quite prolific and you present in a lot of, uh, places as do your other UCI colleagues, but you know, tell us a little bit about that pressure. But then also, what are you excited about? Where is the team gonna go in the next year and where can maybe our outside colleagues see some of their work? Yeah. The the door to happiness uh opens inside. So sometimes you don't have to, um, you don't have to push. Things will come and that's maybe the, uh, penultimate level of the, uh, clinical trial Maslow. You do everything correctly. You do it by, uh, you do it right. Things will fall in place, meaning you open the right trials. Uh, you enroll well, then you're a higher enroller and you get the academic, uh, credit. You write your own trial, that your your trial, you finish it. It's guaranteed that everybody who within UCI will be getting that publication and as a matter of fact, we, uh, we submitted, I think, 10 abstracts to GIASCO which is coming in January, um. Half of those investigating initiated trials, half of those industry sponsored where we did well. So, it takes time, right? It takes time till it matures, but you, you just put your head down and do your work and do it correctly, good things will happen and I think that's been the experience and it's super important to tell junior faculty that the first day you come, you're not gonna get the first author paper. I just was in uh Berlin last week. I presented the first author on a stomach cancer trial with a novel anti-clouding. 182 by specific antibody. I was not because of my looks first author, but because we actually enrolled the most patients globally, right? So, um But I'm now 9 years at UCI, so it takes time, but it will happen if, if you put your head down and just uh uh. And sometimes we tell our patients this is the trial you participated in, you know, you contributed to that data and they get all very, very proud. Yeah, well, it seems like it, you know, it certainly takes a special type of phenotype, sorry, special phenotype of physician to be here, right? Like. Uh, a small group of medical oncologists decide to go through this route, um, and, and so when you guys are recruiting, you know, when the cancer center is recruiting new physicians, do you find that that phenotype is what has attracted here, or do you also have oncologists that maybe aren't necessarily there but like to support the work and maybe don't want to do the actual writing and, and grant writing and analysis, even at the biggest cancer centers like MD Anderson. We had a mix of oncologists with different uh uh uh interests. There are truly academic oncologists who enjoy the patient care, but they don't wanna be sitting down and writing the protocols or reviewing adverse events and grading them, right? But they contribute and a lot of them are have more papers than I do because they contribute so many patients to the trial. So there are sub-investigators on these trials and they contribute and enroll, but they don't wanna have to do all the paperwork and the other things that are associated with it. And when I interviewed junior faculty, I think I give him more. Life experience, and then I interview them, I tell them. Clinical research is not glorious that you say, I'm the PI. I sit there and things happen. That's the reason you have a protected time is to respond to the coordinator in a timely fashion. If there's a serious adverse events, you have to submit it within 24 hours to the sponsor and the FDA. You have to sign off on that. You have to go through these. Adverse event logs, you have to, there's so much associated with clinical research. So these are the things that I tell them that that's why you have a protected time. So, are you, are you willing to do that? And we expect at some point you start writing your own protocols. Now, We have an infrastructure of supporting junior faculty to succeed. So really, um. I try to be upfront with them and when they come, then we know they're actually motivated to do it. We have clinical trial boot camps for junior faculties, for fellows. We have uh advanced uh um mentoring programs for, for mid-career faculty who want to take the next step. So, and the Stern Center provides, uh, logistical support, regulatory support, finance support, and writing support for, for investigiate trials. So we really try to make it as, uh, painless as possible, but. I'm trying to be very upfront before we hire them and say this is what's expected, and when they come as. In that role, usually then we know they're already motivated. So it's like another full-time job basically, right? Like, so you're gonna have your patient care and then this is gonna be all of that on top of that. It's the other 40% where you're not in clinic, but it's not like you're off. Well, I, I know for me I've absolutely learned a lot. I mean, I'm, I am a cancer surgeon here but didn't, don't recognize or don't appreciate everything that goes on behind sort of the curtain of clinical trials, trials. It's a pleasure for me to recruit surgical patients and then. If they and take care of them and if they can benefit from a trial then hand them off or participate in it, but I, I, I, I gotta say this has been very eye opening for me to, to recognize all the hard work that's done not just by the physicians, but I think what you're really highlighting here is this massive team behind you. I mean, 140, and, you know, uh, co-workers there to, to help support the work. I mean that's just a fraction, and then there's everybody else that's, that's there that's not in the Stern Center, so I must say it's pretty impressive. Thank you. I think it's, it's, we're very proud of the SEN Center, but as you say, it's the nurses in the infusion uh uh rooms and there's the PPCU nurses for our phase one trials where the patients have to stay like last night till midnight to have blood draws. You know, it's, it's much bigger than the SEN Center, but the coordination of this is, uh, is a daunting task, but also very rewarding when it works out. So I know UCI Health is growing every day, and I think thanks to, you know, people like you, the national reputation, international reputation is growing as well. Um, one key thing I just wanted to call back to is you talked about sort of our distinct population here in Southern California being special and potentially leading to You know, more patients needing GI cancer support. So for those who don't know or who might be outside Southern California, what are those qualities and do you expect to start drawing more people here? Uh, we actually already started, we, we went from being the best kept secret in Orange in Southern California to not being a secret, uh, for the stopgap trial where we give chemotherapy into the peritoneum. Half of our patients came from outside of California actually. Um, so this is, uh, I, I think our expertise is, is starting to shine through in, in, in specific diseases in, in stomach cancer, and, and liver cancer. And that's reflected by our demographics, uh, 38, 40% Hispanic patients, 28, 30% Asian patients, and that comes with, with relative high rates of specific cancers. And the last point maybe to make is I tell my junior faculty, learn from your patients and then write the trial that addresses them rather than to say, I want to do what I want to do, but I never will see that patient because I don't have that population. It's, it will be a win-win, and I think that strategy has paid off in terms of getting the name recognition out and I have to say I'm surprised where we're getting from East Coast inquiries about our trials and, and we had a patient, I had a patient who was a physician in Michigan, a radiologist. He went on 3 different trials at UCI even. After the first trial, I told him the trial is available at Sloan Kettering in New York, which is closer. I said, no, no, no, I want to stay with you guys. This, he went through 3 different trials and he would fly with Delta from uh Detroit once or twice a week just to come to us. So I think uh uh we are, we are getting more and more recognized for that. Weather is nice too Thank you both so much for being here. That's a great conversation. Learned a lot. I expect that you will just continue to do great things here. I appreciate it. Thank you so much for having me. This has been Physician Huddle by UCI Health. Thank you for joining us. This was an episode of the Physician Huddle podcast by UCI Health, produced by Brett Shaheehan, Angelica Yagubi, and Victor Ting. For more episodes, information on clinical trials at UCI Health, or to refer a patient, view the show notes or visit clinical connection. UCIhealth.org. Created by
