BackTable Urology
Ep. 207 Integrating Clinical Trials into Routine Urology Practice with Dr. Behfar Ehdaie
Tue, 31 Dec 2024
How can urologists run clinical trials efficiently while improving enrollment and reducing costs? In this episode of the BackTable Urology Podcast, Dr. Behfar Ehdaie, a urologic oncologist at Memorial Sloan Kettering Cancer Center, joins host Dr. Aditya Bagrodia to discuss methods and practical implementation strategies for clinical trials in urology. --- This podcast is supported by: Photocure https://www.photocure.com/ --- SYNPOSIS First, Dr. Ehdaie shares personal experiences from starting pilot trials, engaging stakeholders, and integrating trial processes into clinical practice. He also discusses mechanisms to reduce cost and improve enrollment while explaining the concept of two-stage consent to minimize patient anxiety. This episode aims to provide valuable pearls for young investigators and experienced practitioners alike on conducting successful clinical trials. --- TIMESTAMPS 00:00 - Introduction 04:39 - Challenges in Clinical Trials 06:21 - Case Study: Focal Therapy Trial 16:45 - Case Study: Hernia Trial 20:17 - Innovation in Clinical Trials 26:25 - Two-Stage Consent 36:11 - Final Thoughts --- RESOURCES Photocure https://www.photocure.com/
This week on the Backtable Podcast.
I had a fellow once who was really interested in kidney cancer and he goes, how do I become a kidney cancer expert in my institution when I'm going and there's five, six other people doing kidney cancer surgery? Well, I said, go to the cooperative group, bring a high-risk kidney cancer protocol to your institution. You don't need to be the one who wrote the protocol.
You just have to be the site PI, which the overall PI would love for you to do that. The protocol is written. You just need to enroll patients and now you can talk about your trial at your institution. You'll have patients directed to you who are eligible for that trial.
Hello, everyone, and welcome back to the Backtable podcast, your source for all things urology. You can find all previous episodes of our podcast on iTunes, Spotify, and at backtable.com. This is Aditya Bagrodia as your host this week, and I'm very excited to introduce our guest today, Bifar Adai from Memorial Sloan Kettering, Department of Urology. Bifar, how's it going today?
It's great to see you again, Aditya. Yeah, pleasure's all mine. You know, I had the good fortune of training under Bafar when I was a fellow there. Very, very thoughtful clinician, exquisite surgeon, and, you know, my opinion has... properly, methodically moved our field forward substantially, particularly with prostate cancer.
So today we're going to talk about, you know, the technical title is Novel Methods in Clinical Trials. And maybe I'll just extend that a bit into...
practical implementation strategies to study new ideas in a way that's safe effective and perhaps not overly onerous as well so before maybe if you don't mind share a little bit about you know how your interest in clinical trials and moving the needle kind of began
Well, thank you for that. And, you know, my interest in both research and clinical trials is very similar to, I'm sure, many urology residents and fellows who start their career. We want to make a big difference. We understand that retrospective papers and studies are important.
But ultimately, to understand the impact of any of our either decisions, interventions, we need to do randomized controlled trials. And those trials still remain the landmarks of our education when we look back at what we've learned. So our goal and many goals like mine was to just be able to contribute to the field in a small way. And the experience happened, you know, very early on in my career.
As you know, when I completed my fellowship in Memorial Sloan Kettering, I was ready to hit the ground running. And I was fortunate enough to understand that perhaps some areas of research that needed to be done were in both biopsies, this is pre-MR targeted biopsy era that was universally accepted, and focal therapy. And all that tied into my interest in active surveillance.
So I went to London and spent, you know, three to four months with Dr. Hash Ahmed and Dr. Mark Emberton. And it was astonishing to me to see how easily their system was set up for patient enrollment and clinical trials. I remember when I returned, I went to my research mentor, who was Andrew Vickers, here at Memorial.
And I had probably a full sheet schema for a clinical trial that probably had like eight rows, six columns, trying to answer four to five questions. And I thought it was just great. And I remember Andrew sitting back in his chair and going, you put a lot of thought in this, but... This is not how I would approach clinical trials.
And it was at that moment, despite my training in epidemiology and my public health degree during my fellowship, I realized the learning curve is quite steep. And from there on, my interest started.
It is a process and it's laborious. And I guess it's intimidating enough that many people don't ever give it a shot on the one hand. Then a lot of people try and they fail, on the other hand. I mean, I guess they learn something along the process. It's not a total failure. But it could be helpful to take a case example, perhaps one of your early clinical trials.
And let's just literally walk through it from, you know, you're familiar with the disease. prostate cancer, biopsies, surveillance, focal therapy, and you've come up with a question that you think is worth answering. Let's walk through the nuts and bolts of taking that question to a trial.
So, yeah, I mean, your point about trials not accruing or completing is not just a urology problem. It's universal. You know, we know that only 3% of adult cancer patients actually enroll in clinical trials. The vast majority of trials... don't accrue. In prostate cancer and localized disease, for example, we had 11 clinical trials that didn't accrue over the past two decades.
So we knew this was a formidable challenge. But I also understood that sometimes you have to start with some singles and doubles before you try to hit a home run. And the first part, and throughout this whole conversation, I really hope to share some pearls. And the first pearl was you have to ask an important question.
And important doesn't mean, you know, New England Journal of Medicine featured article important. What important means, it has to be important to stakeholders. And the stakeholders are often our patients. It could be our colleagues or clinicians within the field or specific subspecialty that we're working in. And so understanding what that important question is, is the purpose of mentors.
So spending time with them and asking them, where is the puck going? My earliest trial was in focal therapy. It was very clear when I started that the field was just beginning. However, what we lacked was good prospective data, especially in North America. And so when we sat down to begin writing that trial, it was starting with a question.
And the question that we had to answer was, does focal therapy do what it's supposed to do, which is treat the area that we're targeting? And are we able to select those patients? And finally, as we answer that question, how is the patient's quality of life? And to answer that question, I thought we can write the trial. I had mentors to put it together.
But immediately right off the bat, I realized the important question needed to include our stakeholders. And because this was a multi-center trial, we brought everyone together at the very early stages, not to share an already written protocol, but to talk about the skeleton and more importantly, make everyone buy in to the outcome measure. And that was the first step.
We wrote a skeleton draft, brought everyone in a room. It was a Saturday morning in New York City. I remember people flew in. We sat around a table. And when I proposed the idea... the questions directed our trial, meaning they really guided our next steps. And the first question we had to ask was, do we want to do a trial in low-grade prostate cancer or intermediate-risk prostate cancer?
And it was interesting because at the time, this is now 2013, 2014, Although active surveillance was considered a treatment option for men with low-grade disease, there were still questions about percentage volume with Gleason 6, if there's extra capsular extension, if it's detectable on MRI.
And really the idea of Gleason 7 prostate cancer being something that we can monitor or think about outside of radical treatments was not firmly in place. But we also realized that that's the group of patients in 10 years that we will probably be speaking about with regards to focal therapy. So we had buy-in right off the bat that the group of patients we want to study...
Yeah, I mean, it's easy enough now to say that's a no-brainer. And a focal therapy trial conceived today on September 26, 2024, including grade group one patients would probably get a lot more pushback in terms of, you know, you're exposing folks that should do extremely well to some harm is generally, I think, accepted. So...
I mean, to me, it highlights an important point that, you know, getting it kind of right-ish off the gates, maybe even taking a bit of a gamble in terms of what's this going to look like. You know, it's so easy to look at a trial that was conceived 10, 15 years ago and slice and dice it to bits because of the methodology involved. back then, but it sounds like you made the right call.
And I'm sure that was a big call. And if I may, I think these days, appropriately, the key stakeholders absolutely involve patients as well. It's really been nice to see over the course of our careers that having the advocates at the table, the stakeholders is key. All right.
So you decided looking at essentially oncologic outcomes, quality of life outcomes in patients considering focal therapy was going to be the way that you go. Fair. And maybe one other question before, you know, this is something I kind of struggle with. It's like, do you provide a skeleton to keep the conversation moving? Or do you kind of leave it open ended with all the opinions?
And many times, there's so many opinions that you never make any progress. Can you talk a little bit about that balance?
Yeah, so obviously the first pearl is make sure the stakeholders are involved at the very beginning to help form the appropriate or important question. But within that, a small group is always better than a big group. I've been involved in consensus meetings where you have 20, 30, 40 people in a room, and you're right.
There should be a lot of conversation, and finding consensus is extremely difficult. But starting with a smaller group is the key. And so although we had a skeleton, we knew what direction we felt the discussion should be led. And we just provided some of the input, some of the data that helped people in that room understand. and help ourselves get to the right answer.
And so although I could have started that meeting saying we should treat only intermediate-risk prostate cancer, I think the data that was presented, the conversations that were had, not only allowed us to see a new perspective, maybe something we didn't consider, but it helped everyone else get on board because, frankly, they own that idea as well.
So we were able to determine the eligibility criteria in one meeting and discuss what's the next steps. And I think what we didn't realize in the other parole is that we were trying to write a trial like you see every other trial written, which is off the bat, millions of dollars, lots of eligibility criteria, lots of exclusionary criteria, triple checks and double checks for every step.
And that turned out to be something that was eye-opening. This trial that we started in 2014 and 2015 that ended in 2018 or 2019 cost over $3 million to put together to enroll only 101 patients. Obviously, that's not feasible for many investigator-initiated trials.
So I realized early on that these trials that are outside of clinical practice, meaning we have separate assessments of quality of life, we need research study assistance in every step of the way, patients are not going through the same pathways as our straight clinic pathway to be enrolled and consented and the trial discussed wouldn't be feasible unless we do one of these trials maybe in our lifetime.
for each individual clinician who's interested in trials. And that's when going through this trial and subsequent trials, I realized our trials need to be integrated in many ways to our clinical practice.
And this was a pioneering concept that was championed early by Andrew Vickers and Peter Scardino, who were able to upfront tell us what the outcomes we measure in trials are often the outcomes we measure in our clinical practice. So if we want to look at radical prostatectomy outcomes, we want to look at biochemical occurrence, positive surgical margins, sexual function, urinary function.
And why not, in every modification that occurs in the operating room that surgeons do every day, Why not just record that, randomize patients or the surgeons, and look at those outcomes as we would anyways without the need of research study assistance or other factors that really make the complexity of clinical trials very expensive?
Yeah. I mean, I was exposed to this where patients receiving prostatectomy, for instance, and I'm sure we'll talk about this, would basically, to over-summarize, sign a bit of a global consent for interventions that we would consider non-major, if you will. And that's clearly where some...
interpretive latitude is allowed and then they'd get their procedure and maybe they'd have their prostatectomy extracted via vertical incision or horizontal incision maybe they'd have a certain type of lymphadenectomy maybe you know some of the newer things ish coming through the pipe
Retzius sparing versus traditional posterior approach or anterior approach or hood sparing, you know, God knows what that is well within your right as a surgeon to try to offer the best oncologic and functional outcome. Now they've been properly studied.
So maybe I'll ask, you know, when you're thinking about this, if I've got it right, how do you kind of decide what is a reasonable shade of gray versus this is really something beyond a typical modification within a standard that needs separate consent, infrastructure costs, et cetera, that you're kind of alluding to?
Yeah, so as we think about clinically integrated trials, our outcome measures need to be something we record as part of clinical care. Nothing separate. Our eligibility criteria should be very similar to the patients we treat every day. In this specific trial that you're speaking about, which was our umbrella trial and modification of radical prostatectomy, You're right.
We were looking at modifications that surgeons do every day in the operating room, but we don't record. Oftentimes when we do, we do a before and after study and say, I've done this 200 ways this way. Before I did it a different way. Here's my retrospective study outcomes. Well, we decided let's ask those questions prospectively. And the modifications had to be decided upon by the group.
Oftentimes, a modification that six, seven, eight other surgeons also agree on incorporating is probably not a large deviation from the intervention itself. You know, we're not telling radical prostatectomists to do focal therapy as a randomized arm. We're asking them, for example, to do retia sparing on cases or not do retia sparing.
Or like you mentioned, when we close the incision port, instead of closing it vertically, close it horizontally to see if we can reduce infection rate. So these modifications, when you get to the point of asking a group, again, getting the key stakeholders, organically become modifications that can be incorporated and can be seen as standard of care.
Having said that, most of these trials are not comparing A versus B with both our experimental or intervention trials.
We're always comparing to a standard, and that standard is what we've been doing, a standard of care, with a slight incremental improvement that we perceive but hasn't been proven yet, which really brought us to the second trial that we really enrolled in, which is our hernia trial. So, again, the idea sprouted.
The importance of the idea was a retrospective paper we did in SEER in which we found that approximately... 7% of patients who get a radical prostatectomy in the United States have a subsequent hernia operation, umbilical hernia incision repair within three years of the operation.
So almost one out of 12 men getting a radical prostatectomy and go on to get a secondary surgery due to our intervention. So we asked the simple question, can we improve that? Well, the literature provides some guidance. So we knew the question was important to reduce even 30%.
That number would be a significant improvement in patients' lives, a quality of life, cost to the healthcare system, burden of treatment for patients. And there was data to suggest A is standard of care and B is standard of care. We just didn't know which one was better. So we launched the concept, let's go ahead and do a cluster randomized trial.
We already assessed hernia after surgery at both the six-week follow-up, six-month follow-up, and one-year follow-up as part of our notes and systematic approach to seeing patients. So why not up front? tell surgeons that we randomize every three months to say, now close your incision vertically or close your incisions horizontally.
This is not an earth shattering study that will change the future of prostate cancer. But because it's not, it can't be an expensive trial. It can't be a burden on surgeons. It can't be a burden on the healthcare system or patients. So it's these small questions that are still important and can direct our clinical management can be answered if it's already integrated in our healthcare system.
So in this study, all we needed to do was we had the outcome measure already measured. We had patients eligibility criteria based on who we take to radical prostatectomy. All surgeons were on board. And so we would randomize a surgeon every three months to do it one way or the other. And if they deviated,
because they felt the patient needed to do it one way for some clinical reason that they had that we didn't want to adjust, they would just record that. Say I was, for example, randomized to vertical, but I did horizontal enclosure for this patient for XYZ reason. And that's why in our consents with patients, we always state, we don't know what's better. That's why we do these studies.
But in the operating room, this trial that you're signing up to will not alter what a surgeon does to you if they think one way is better than the other. All we're doing is asking for your permission to collect data to determine if the intervention made an impact. And so that trial enrolled over 1,400 patients over a three-year period, but was interesting.
We enrolled those patients through the middle of COVID. So without research study assistants in the office, seeing patients virtually, without our infrastructure that we're fortunate to have at Sloan Kettering, but were not available during that trial. But the trial continued to accrue because we were still taking care of patients.
And so that was another pearl that by decluttering the clinical trial process, making it more part of what we do in an integrated fashion, we can enroll more patients, we get more patients access to trials and answer questions that are not deemed landmark questions, but important questions because the cost or incremental cost is very low to our healthcare system, including our resources.
Yeah, I love that. I mean, you know, to maybe exaggerate a little bit. And if we took that same study and did it kind of through a more typical mechanism, let's just say the patient's been decided they need a prostatectomy and you have to get all these tests, audiometry and liver function chemistries and whatever. Then you get randomized.
Then you have research assistants that support these trials for three years. You have kind of all this stuff, this clutter, if you will, baked in, which makes it onerous to the research staff. The cost can become prohibitive immediately. And you end up saying, is it worth spending $2 million to try to answer this question? Not only is it worth, can I get somebody to pay that?
which is another tricky one. But it's almost like if we can just use a little bit of common sense, there are checks and balances to make sure this doesn't go rogue, I suppose. And it sounds like there's a kind of an oversight committee. You can answer questions that are worth answering without making it so intensive, laborious, cluttered, as you say, so that it never gets off the ground.
And to your point, A lot of what we do is based on what has been done in the past. So we just follow that same model.
The other aspect, and I'll throw another pearl, is that I really think joining research council committees, IRB committees in your hospital will open your eyes to not only see sort of the breadth of research being done in the institution, but how clinical trials are being scrutinized. I sat on the Research Council here at Memorial for five years.
The most we would scrutinize is eligibility and exclusionary criteria as part of a trial. And that would be a reason a trial would go back and forth with the investigator, give edits, come back to the Research Council, give edits, go back. And then we prolonged approval for three to six months just talking about liver function tests.
Part of what we do in clinical and creative trials is actually to eliminate almost all eligibility criteria and exclusionary criteria. Typically now, when I write a trial, I want one or two lines of eligibility and exclusionary criteria because what we're trying to answer is patients that we are treating now. So the eligibility is a patient that I'm already treating.
I've already determined eligibility. And so everything gets scrutinized. Everything that's an exclusionary eligibility criteria, remember, a research study system has to sit there with a checkbox. with every patient and make sure those things don't fit in those criteria. So we've now really emphasized, eliminate things that are not necessary.
There's no reason if you're doing a clinical trial of hernia repair to include liver function tests as an exclusionary criteria or checking an INR. Those things are done routinely for every prostatectomy. If a patient's a prostatectomy candidate, those steps have already been passed. So we sort of think two steps ahead and say,
If we're integrating our trials, let's integrate how we manage these patients and how we select patients.
Yeah. I mean, it's one of those things that's obvious and it's not. I mean, this is separate, but perhaps related. At many institutions now, a blanket IRB for retrospective studies that pose zero risk to a patient are disallowed. Or biospecimen collection protocols may be challenging to get through. MTAs, DTAs between institutions can be a little bit complicated. And
I guess, you know, just reflecting back in America, I think a few bad apples can really screw it up for everybody. You know, a perfect example is, in my opinion, when you go through the airport, you can't take something more than three ounces. You got to take your shoes off because somebody once upon a time did some stupid stuff with shoes and a small bottle of whatever. I mean, is that it?
Are we kind of handcuffed in so many ways because some of these things have gone awry when providers are given latitude?
So there's always a purpose behind every regulatory action or sort of dogma. But I think what we've learned over time is we need to challenge dogma because things have changed in time. Clinical records and assessment of electronic medical records has changed. We now, at the tip of our fingertips, know what everyone's allergies are. We know what past medical history they have.
We don't need to re-interview every patient at their follow-up appointment because we know their previous note is in the chart. So I do agree that there needs to be thought put in, and there always is, about adding or subtracting any inclusion or exclusionary criteria.
But if we start from the baseline, less is more, I think we can, even if you reduce it 10%, the list of items that you put on that inclusion or exclusionary criteria is critical. Oftentimes, even though the Research Council spends time on that section, investigators cut and paste probably from other trials and just add those things as routine.
So if you've done that, take a minute, because even though the inclusion, exclusion criteria may not be important up front to you as you write your trial, It will be a time and administrative burden in the future because every one of those criteria has its own paperwork that needs to be signed off and checked off from a regulatory perspective for every single patient.
So by reducing those, you've reduced paperwork, you've reduced administrative burden. But the other aspect of this is the burden on our patients. We transitioned from clinical integrated trials to this concept of two-stage consent. And the idea behind that was really when we sit there as our traditional consent in a randomized trial, we say, this is this new idea. It's really cool.
I'm really excited. I want to dedicate the next 10 years of my life studying this. This is what it is, and these are its risks. Oh, by the way, here's this other thing that I'm trying to move away from, but I'm going to balance with equipoise, talk about how this is just as good and has these risks. And a patient leaves those rooms, and now there's many sources of data that show this,
with this burden of information that creates anxiety, that creates an inability to fully understand what they're reading or trials they want to enroll in or not enroll in, which actually reduces enrollment.
It reduces patient autonomy because now they don't feel they're making that decision on their own, especially if they're not there to investigate everything that's been told or if they remember everything. So we said, why don't we just remove the burden of that initial conversation? And so the concept was, up front, let's tell patients that we're dedicated to, for example, we had a trial, again,
We talk about singles and doubles, especially low stakes trials. I was very interested in improving pain and discomfort in our biopsy room. And you've been there with us when you were a fellow with Casey as our ultrasound technician. And, you know, the patients, especially when active surveillance was growing, were getting lots of biopsies.
And it was the number one complaint of every active surveillance patient was, you know, I love not having radical treatment, but God, this thing hurts. So we were like thinking of different ways to improve it.
And one concept that came up was, why don't we get our integrative medicine folks who do this with pediatrics and they figure out ways to reduce pain and discomfort for, you know, bone marrow aspirates or other things through basically the power of mindfulness. Let's get them involved and create tapes that patients can listen to during the biopsy procedure and do a mindfulness exercise.
Well, that's a low stakes trial. Obviously, no one's going to have a massive adverse event from that. So we thought that was a good trial to randomize patients and use this concept of two-stage consent, which was saying we would consent patients to say, we are interested in reducing pain and discomfort and improve the biopsy experience.
And would you sign up for us to approach you in the future at random if there is something that may benefit? And today you're signing up for us to continue to monitor your outcomes and record those as part of a clinical trial. Of course, no patient says no to that. There's no intervention. There's no secondary study. And all I'm asking for is record your outcomes.
And then after they sign that consent, they go home. They get placed in our pool of patients in our trial for biopsy experience. And we randomly select one group that we approach at their biopsy and say, hey, remember when we spoke about our initial discussion that we're looking for ways to improve and we may randomly select you for something if we think it might benefit you?
Well, you were selected and this is the intervention. We're going to give you a headphone. You're going to listen. Are you interested in enrolling in the study? There's no 50% chance that patient's going to get the other side of the token. At that point, they just need to hear about what they've been randomized to because the other option is just standard of care, go do your biopsy and leave.
So that conversation, when it's easier, I was allowed to be excited about this new intervention and speak to them and answer their questions. They were well-informed and then we would collect their data. And it essentially is a randomized controlled trial because those patients were randomly selected after enrollment.
And I remember we looked at this data, which we published recently, and looked at specifically patient anxiety, patient understanding clinical trial, feelings of autonomy, and those were off the charts compared to traditional randomized controlled trials that we use in historic data.
So it was very clear to us that reducing the burden at the time of consent actually created more informed consent, less anxiety, and increase our enrollment into clinical trials. And so that was the next pearl, which was to really take the concept of the standard randomized controlled trial discussion and modify it to this integrated trial if you're comparing it to a standard of care procedure.
I mean, it sounds simple and it's genius. You saw me smiling. For our listeners, they obviously couldn't see me smiling because it is tough, right? When you're approaching somebody for a trial and you're excited about the new and you're trying to couch that in a balanced type of discussion, it's challenging. Yeah. Yeah, I love that.
So, you know, just to kind of maybe dig into this a bit further, the consent is actually taking place at that first introduction of the concept that we may reach out to you about interventions to improve the biopsy experience or the systo experience. And then... Your recording outcomes, which seems to be a critical common theme here. Then you intervene.
Maybe that's warm irrigation for a Sisto versus room temperature. Maybe it's headphones. Maybe it's, you know, I don't know, picking their favorite playlist on Spotify and you go with it. And then at that time of the intervention, so to speak, the system, the biopsy, the whatever, music in the OR, you're saying, okay, now we're going to intervene. Is that still okay? You're excited about it.
You collect the outcome and you're cruising. Does this sound about right?
Yeah. I mean, the second consent is a full consent conversation, but directed at the actual intervention without really... clouding that with the information from standard of care. So you can now even imagine not just looking at, let's say in this case was a mindfulness approach. You can consent all biopsy patients in your institution.
And now instead of just having a mindfulness intervention, let's say you want to compare Flomax versus no Flomax for all patients. So that could be a secondary randomization that's also occurring in the background. So you can approach a patient and say, Oh, by the way, there's two things that we think may benefit you. The first is we'll put this tape on and you listen to it during the procedure.
And the other one is this medication that we would put you on afterwards to see if it reduces your risk of urinary retention. The point being is each one of those are separate outcomes. One's looking at pain, one's looking at urinary retention rates. They're separate. They're not going to interact with one another.
Now you have multiple randomizations occurring, and your standard of care group is still the standard of care. So that's your control group. So you're basically, in many ways, creating multiple trials within a large cohort. This was initially described by Dr. Rawlings years ago called multiple trials and cohorts trials. The problem was is that... It was still randomized trials.
You still had the regulatory features, the clutteredness of follow-up. But what we decided was we will do this two-stage consent and combine it with our clinically integrated trials, meaning we're still collecting this patient's data and information outcomes as part of routine care anyway. So there's no incremental cost after that initial setup of all these measurements for each additional patient.
So we were able to run the secondary trial of the headphone study. We enrolled 280 patients in one year, published that data recently. And again, the cost was just the cost of getting the trial up and running. Everything else was part of our standard of care. This was a randomized control trial. For your information, it did not show a benefit in mindfulness for patients.
I think the discomfort was still uncomfortable. Of course, we transitioned to transperineal biopsies in clinic now, which are its own challenge. But the point is, we were able to run a trial again, low cost, greater cruel. And remember, when you talk about a cruel, I don't think of just about a cruel for a trial. I think of it as from the perspective of access.
Now, almost 80% of our patients who are getting biopsies at Memorial Sloan Kettering had access to a trial as opposed to, oh, I forgot to tell this patient about our trial. I was a busy day in clinic. I was running behind, so I couldn't really talk about this. Or, oh, our fellow didn't discuss this with the patient.
Every patient was being approached as a standard act by our research team all under this umbrella protocol. So it took away the human factor that I think impacts access. And of course, by decluttering the initial consent, patients felt autonomy. They had better information. They felt in control.
And they understood at a very basic level what we were doing and what was happening to them, which not surprisingly improved accrual because those patients would say, yeah, I think I want to be, I understand what's going on and I want to be part of this trial.
The patients who chose not to be part of that trial would probably not choose in any other form because they didn't want any of their outcome measures being recorded as part of any data collection. So that was very separate and that was a very, very small group of patients.
No, I mean, these are tremendous pearls before. I mean, the clinical integration of trials, the two-stage consent. What are some of the other things that you feel have been particularly effective in your illustrious clinical trials enrollment career?
So, I think some of the other pitfalls that you learn most about was you have to make sure you meet with your clinical research team bimonthly. So every two weeks, even if you've only enrolled one patient in any trial, it is worthwhile to get everyone in a room, or nowadays on Zoom,
And have a conversation because A, there's a lot of blind spots you may not be aware of that your research study assistants are aware of. Or if there's a medical student working with you or a resident or fellow. B, it keeps people engaged because there's an update that needs to be provided every two weeks.
And it allows everyone to reflect on what we're doing and create pride, especially if there's really things are moving in the right directions and everyone's doing their work and all those things sort of support one another.
It can't be, you know, once every quarter when I have to report my information to the IRB, I'm going to hurriedly get a meeting together, get the information from my research study assistant, quickly send an email to the IRB. That doesn't work. So I tell all new investigators, make sure you have regular meetings.
And I think bi-monthly is a very good cadence in our world, especially as busy surgeons. The next factor is when you think of a trial, always think the idea of pilot trials. We want to run before we walk. And some of the ideas we have are really good ideas. I mean, I have, obviously, as you know, some of the most brilliant individuals that I'm fortunate to work with as fellows.
And they come in every year. It feels like they're so prepared academically and they're ready to answer some of the most important questions in our field. And they're ready to write that 800 patient trial. And they probably will do a good job writing that protocol. Yeah.
But I always tell them, well, there's so many things we don't know, and getting this trial through an IRB at these numbers is probably going to be a long process because there is a lot to take into account. Let's start with just a pilot phase. Let's start with a small group. Let's learn. Let's see how we're doing things. And frankly, pilot study...
is seen very differently from a regulatory perspective than a large randomized phase three trial. I tell everyone, before you jump and before you start running, walk and start with that initial pilot trial.
A lot of our grants, what we write in clinical trials, we do a 20-patient study, prove that we could randomize patients, make sure patients understand the trial, and we worked out our multi-center group of institutions that we all communicate with one another.
Makes sense, right? I mean, you see perfect examples of that. You know, one recent one that comes into mind is the recent BRIDGE study comparing BCG versus gem dose C for non-most invasive high-risk bladder cancer. The study PI did a small pilot at their home institution. It went well. And then through the cooperative groups, we're able to get something substantial moving.
I don't see it as a sellout to test the waters and see how it's going to go, you know, because we've seen amazing, ambitious trials, a dime a dozen, unfortunately, answering really critical questions that just never got off the ground. Fantastic before.
So, you know, as we approach an hour here, you know, I wanted to maybe just have you run through, you know, lessons learned, things that work, things that didn't work. You've touched on some of the pearls and some of the pitfalls, but any that we didn't cover?
I think the last part of this, and I tell this as a role as a mentor now, of course, when you came as a fellow, we were colleagues. I don't consider you my mentee. You came in fully credentialed, excellent surgeon, and I think we worked together on cases and actually discussed things all of the time in the OR. But I feel like as my hair has gotten whiter, I'm expected to be more of a mentor now.
And so in that role, the question I'm often asked is, how do I get my trial career up and running early? You know, and so I say it's actually very similar to becoming, you know, a expert in your own field. And the way you do that, I've always said, is you need to be considered an expert by not the International Academy of Surgeons, but really locally.
When the person who vacuums the floor of your office building, if they have a family member that has prostate cancer and they come to you and they say, can you take care of them? You've actually turned out to be a local expert at that moment because they chose you. So how do you become a local expert, which is critical? And the way I think you do that is you go to cooperative groups.
Go to your, find your cooperative group. Those meetings are open. They're an incredible collection of individuals dedicated to patient care. This is not a meeting where everyone's presenting their paper of the week. You know, these are people really there for their patients thinking about trials. And go and bring the trial in your disease area.
I had a fellow once who was really interested in kidney cancer and he goes, how do I become a kidney cancer expert in my institution when I'm going and there's five, six other people doing kidney cancer surgery? Well, I said, go to the cooperative group, bring a high-risk kidney cancer protocol to your institution. You don't need to be the one who wrote the protocol.
You just have to be the site PI, which the overall PI would love for you to do that. The protocol is written. You just need to enroll patients. And now you can talk about your trial at your institution. You'll have patients directed to you. who are eligible for that trial.
So as a young attending, now you're seeing every high-risk kidney cancer patient because your institution says he's got the trial or she's got the trial and we need to get them into your study. And right there, as soon as you get that first traction, you understand how a trial works.
You're working with the people behind the scenes, but at your own institution, you've become now the site expert for advanced kidney cancer, for example. And that, I think, is the easiest launch point, especially in the first six to 12 months of your career, to get into clinical trials, become an expert in your field locally, which is critical.
Stop worrying about regional expertise, international expertise, and hit the ground running.
I love it before. And I can think back to the early days when I was just starting and kind of knew that germ cell testis was going to be my primary area of interest. And the SEMS trial was just kind of getting going. And I reached out to SIA. We opened it there. And I was literally so thrilled to put four patients on. And that did give me some validity within my own kind of institution, region.
kind of got things going. So I think it's super sound advice, whether it's multi-institutional IITs, co-op group trials, get out there, see what is exciting to you, interesting to you, and then you knock it out of the park. And maybe I'll just also add, I think in the spirit of always improving, don't be intimidated. It doesn't need to be, like you said, a grand slam from the get-go.
It could be a QI project that you're like, huh, that seems compelling. I would like to disseminate this. And then you can look at different mechanisms. Well, before, you know, thanks. I knew it was going to be a thoughtful, reflective conversation on other things that have worked well and some of the pitfalls as well. So I appreciate your time.
Great to see you again and look forward to connecting soon.
You too.
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