How to start clinical trials/research as an ancillary in gastroenterology
Over the past few weeks, I spoke to not one, but three physicians who are deeply involved with clinical trials in gastroenterology.
◘ Dr. Narayanachar Murali, Gastroenterology Associates of Orangeburg (South Carolina)
◘ Dr. Don Lazas, Founder and Chief Medical Officer, ObjectiveGI (Tennessee)
◘ Dr. Chris Fourment, President and CEO of Clinical Research Strategy Group and Precision Research (Texas)
In this interview, you’ll learn three different perspectives on clinical trials/research as an ancillary in a GI practice. We’ll explore the pros/cons, costs, risks, and operating models.
Consider this interview as a primer on starting up with clinical trials/research. In the coming weeks, we’ll release more detailed interviews on the topic.
The Transcribed Interview:
Praveen Suthrum: Hi, my name is Praveen Suthrum and I am the President of NextServices. Thank you for joining me. What you’re about to see are three interviews with the GI leaders involved with clinical research. Like many of you, I have been very interested to learn about what is the right way to go about building a clinical research ancillary in gastroenterology. In this interview, you will meet three people. The first is Dr. Murali who is a gastroenterologist based in South Carolina and he has done clinical research for the last 25 years and you will learn how the field has evolved over the years. The second interview is with Dr. Don Lazas, a gastroenterologist from Tennessee and he’s also the co-founder of a company called ObjectiveGI. ObjectiveGI helps GI practices get started with research initiatives. And you will learn about why he began his company and how to work with them. The third interview is with Dr. Chris Fourment. From the beginning of his career, he has been focused on clinical research as an ancillary. He has worked with large groups such as Texas Digestive and helped them develop their program. He is today the President and CEO of Clinical Research Strategy Group and Precision Research. Like me, I’m sure all of you will find these interviews very insightful. If you have any comments or questions please feel free to leave them and I’ll be sure to get back. Thank you.
Dr. Murali: So, when I was in training, I used to be very closely aligned with the clinical trials manager at the University of Kentucky where I came from and professor McClain who has so much foresight and is an amazing mentor encouraged us to be deeply involved in these trials. You know, we were not just hanging around doing sundry work but he made us understand what trials involve, how it is done, what is the ethics. We got a good grounding in it. So, when I started my practice it naturally came to me to seek out clinical trials. Of course, everything has changed. We used to do these trials quite easily in those days because there was less paperwork. So, I started my first clinical trial in the first year of my practice. For some reason, I was very busy from the first day I started. So, by the third month, I was seeing a lot of patients and initially, there were a lot of drugs that were being tested for… reflux, for ulcers, for heartburn, for Hepatitis C. We got involved in almost all of the trials and for some reason sponsors also tended to gravitate towards my practice. So, I’ve always had a steady interest both from patients and especially from the sponsors.
Until about 10 years ago the paperwork was manageable. Today they have created multiple layers so you not only have the same or more paperwork but you have more scrutiny. And the need for a very accurate paper trial to support your electronic documentation it’s the other way around. So, we have to have three systems one is the study binder which has to be still and it’s around five with all kinds of information. And every paper in that has to match what is in the electronic case report form which is there in the EMR version of the whole thing. And third, as you know in my case, I maintain records through chronological PDF files so it has to match that as well. You have to establish SOPs for everything you do i.e. Standard Operating Procedures. So, that you have a uniform policy of distributing information, authenticating your papers, and being able to account for what you do. It is very hard. If you just have some EMR, you can’t just do that. It’s very hard.
So, you would think an EMR would make your life easy but it can make it very complicated. So, now what the trial designers have done is… they have replicated the paper version using the electronic version. So, we’re supposed to keep all these records for many years. Come to think of it the amount of storage space that I need has become a big problem for me. But as many trials as we have done over the years, I have these boxes which contain all these materials, we send samples and they all take up a lot of space. Everything is sent frozen. So, you know these are bulky containers, I can’t squeeze them I can’t compact them. So, all these things have to be thought of. So, it takes up usable space in my office.
I do these trials for only one reason which is to stay ahead of the game and to offer my patients the very best of options for treatment. You know, today my focus is completely on Inflammatory Bowel Disease. So, I have concurrently about eight or nine clinical trials going on in my practice at this time. So, there is a steady flow of patients, very busy. And as you know my wife, Anu, who is a scientist. She gave up her job to help me. Today, she is the Trials Director and she’s also the sub-investigator on all of the trials with me. She wears so many hats without her I would be doing nothing. So, she really helps me do all the trials correctly and she understands all the regulatory matters very well because she’s an MScR. (Masters by Research)
Advice for starting clinical trials:
It depends on the size of the practice. In a large practice, you can afford to hire a full-time staff to direct the trials, then you can hire subordinate staff to do the blood draws, to handle specimens, to do the ECR of entries, all these things and you can delegate the work. Remember that all comes with payroll, right? So, you’re increasing the payroll. Clinical trials are not a way to make a lot of money. Although, it may seem like that, you know if you just look at the raw numbers you might say “Oh my gosh! You got paid a hundred thousand dollars” or more but then how much of it is going towards other expenses? So, it is a labor-intensive task, and if your motive is to make a lot of money look elsewhere.
Number one is to have a very good Trials Manager who is willing to do a lot of other things early on in the business. Because initially, you will not be very busy. So, when you’re having only one or two trials you can’t afford to have the level of staffing that big organizations have. So, the person should really work closely with you and there must be a clear understanding between the PI (which is me) and my staff as to what their delegated duties are. They have to put the patients first. We need to have the patient volume to support the trials. For example, because of my focus on IBD, I have a very large IBD practice. So, I see a lot of patience with Inflammatory Bowel Disease and many of them come from the three-state area to my practice. So, if I want to recruit it is very easy for me to recruit patients.
I don’t usually advertise, I don’t go through other routes, I don’t try to call doctors to refer patients to me, I don’t do any of those things. Fortunately, we have a steady stream of patients some of them very sick, some of them are not responding to current drugs. So, there is a huge need and this has really helped these patients. So, what you do… is at the beginning, even before you do anything, you sign the non-disclosure agreements, you look at the trial design. They’ll send you great detail about what it is all about. You will usually get a floor sheet that will tell you what is the order of things that have to be done.
You should have good cost accounting knowledge in order to budget correctly. Everything is negotiable. So, you have to know your operational costs over and above your cost per unit time of operating your business. So, in my case, I have an integrated practice with both endoscopic services, clinical trials, and clinical practice all in one roof. So, I understand my cost pretty well. You must account for this time that is wasted and time that is taken up with the trials. It is not as simple as – I see a patient, I write a note, and I’m done. There will be so many queries back and forth no matter how meticulous you are. You are going to have queries coming back to you. Each one of those involves logging onto the computer, answering questions, referencing your source documents, clarifying things, repeating labs if necessary. It is very involved. It is not easy; honestly, it is not easy at all. Somebody has to be there to help you.
Of course, with clinical trials you’re exposing yourself to litigation as well, right? So, you have to be aware of that. You have to know where your comfort level is, what is your knowledge is, how do you manage complications? You need to have a standard operating procedure. So, you need to have a policy and procedure manual in place much as the hospital does. You have been to my practice and you have seen how in-depth everything is, right? So, that is how it has to be. Without that level of connectivity to information and the patients, you can’t do these things.
Dr. Lazas: Well, I think we’ll start with the ‘Why’ first. Gastroenterologists traditionally have understood the value of ancillary services and with consolidation efforts to stay fiercely independent. Whatever your track is with your practice as a gastroenterologist, we all realized the value of ancillaries and sophisticated practices have really built their businesses around extending services around new ancillary lines. The biggest one of the bigger challenges in the ancillary world has been – research. And there’s a reason why only 5% of practices have clinical research and you can talk about some of these challenges. But there’s tremendous upside for research and we see it as a transformational ancillary service in gastroenterology that can really transform patient care that’s part of our tagline at ObjectiveGI. There’s also a tremendous need in the research community in terms of Pharma, a tremendous shortage of qualified sites to conduct clinical trials in most areas of research.
So, really a tremendous opportunity but there are challenges and we stepped into that void to really address the need we felt… that a platform for conducting clinical trials and in the busy workflow of practice wasn’t in order. So, we set out and created ObjectiveGI. We built this at the point of care. My Co-founder and our COO, Colleen Hoke, and I started this company really with a few premises in mind. First of all, we knew that clinical research was most effective, and most valuable when inserted at the point of care in an integrated way where the clinical research literally runs alongside of the clinical team in terms of the day-to-day patient care.
We learned that patients were endeared to this model, they were seeing their physicians more often as an investigator, they were getting education about chronic silent diseases like NASH and their patient engagement experience was really tremendous. So, it really added value to the care paradigm. Second, when we built ObjectiveGI we knew that we had to build a research platform that could be integrated into the workflow of the gastroenterologist. We’re busy transactional doctors, we’re thinking procedures, were thinking how can I get out of the clinic to my ASC to do my scopes, And I understand that having done it for almost 25 years now. So, we knew if we were going to conduct research it had to be done in a workflow friendly way.
The future is Chronic disease management.
We also wanted to select diseases and disease states that really were the future of GI. So, as we know it now, we’re being encouraged and directed to take care of the metabolic syndrome as gastroenterologists and bariatric care, and really the future is chronic disease management. And so, as we started thinking about our focus and interests, we knew that we wanted to be around the management of chronic diseases and oriented towards metabolism disorders and fatty liver disease of course fits that mark quite well.
We now have 14 sites across the U.S. involving approximately 150 providers we started with NASH, I’m sure we will talk about disease states and why in a moment but we have been involved in over 25 NASH trials so this is rather complex research. There’s a tremendous need for this work. There are over 100 NASH trials currently underway. And, five large phase-three trials that will be starting in the coming quarters. So, there’s a tremendous opportunity here for us to do this work across our site network. For instance, if you think about the bariatric care program in a GI practice, it’s easy to start slinging balloons down but if you don’t have a foundation on which to build a sustainable program in bariatric care then you are kind of stuck. But research really foundationally is the most credible way to lay the foundation for other and additional ancillary services.
Traditional joint venture model:
So, it’s a traditional joint venture model. Gastroenterologists are very familiar with this model in terms of the ASC structure. It is far less capital intensive than say starting an ambulatory surgery center or even a pathology lab. Of course, the capitalization is based on ownership in the joint venture partnership. We establish a separate LOC. We have separate banking. Finances are completely transparent, there is no skimming off the top, and it’s not an MSO model. Of course, there are expenses to the joint venture which include fair market value payments to physicians which is the clinical side of research so physical exams, interpreting EKGs, laboratory testing, and some of the training that’s involved. And we have a Medical Director in all of our programs. So, there’s fair market value payments to physicians, there are stipends to patients, there are occupancy costs. On the expense side, we really love to lease space either in the footprint of the GI partner or very close to or in proximity to them. That helps with the workflow. We talk about streamlining and workflow efficiencies, right? It’s good to be embedded or near the practice.
We typically require about 1200 square feet to build our research centers of excellence. And additional expenses will be, of course, employee expense. It is important to note that we hire, train, and manage and then lease back the employees to the joint venture. So, that’s another really critical aspect. And then finally there may be other expenses in terms of leasing. For instance, if we need to lease a fiber scan, our NASH research really requires a fiber scan for all our programs. So, we can lease them through that joint venture. But all of those would be expenses.
The profit-split is based on ownership. We typically like to partner with groups that are five to 30 providers in size. It is important from the standpoint of having a few people. We start with one principal investigator and we like to have two to three sub investigators. When it comes to investment it is typically going to be less than $100,000 on the practice site. We put in our money first. Our partners can invest their money incrementally as needed and we’re very flexible there. And the capital really is spent on standing up the site and getting it going. It takes about $20,000 to outfit a research center in terms of laboratory equipment, and we have to hire and train the employees, we have to lease the space, and then we have to court our sponsors, clients in terms of notifying them that we have a research center. Identifying the trials that we think would be best suited for that new study. Then getting the pre-site selection visit where they sort of review the site, and qualify the site and then awarding the trial and then having a site initiation visit and then subsequently having your first screen and that’s the first revenue event. So, that whole trajectory takes about four months. Most of our research now is in NASH and those trials are very competitive in terms of not enough sites for sponsors and as we’ve developed a network, we have been able to command a premium.
Three parties sign the contract:
So, three parties sign the agreement – the Sponsor, ObjectiveGI, and Principal Investigator at our site – in as a representative for the site. So, the principal investigator has clear responsibilities that are well known and well established in clinical research. They are responsible for oversight of the trial. They’re responsible for doing the clinical work, the clinical aspects of the trial, the record-keeping, reviewing labs, and regulatory and compliance issues, which we support very significantly through our platform.
Working with ObjectiveGI:
Now, what does ObjectiveGI bring? We bring the sponsor relationships. We have very deep relationships at the top of the scientific and clinical teams in the largest Bio-Pharma companies in the world down to very small Biotechs in the NASH space. We bring those relationships, contracting, negotiating the contracts, and budgeting. We have a Quality Assurance team that oversees and monitors and provides training and quality. Of course, we hire and manage the employees as I mentioned earlier and they’re leased back to the joint venture. We do revenue cycle management for clinical trials. We do a lot of internal training for our staff and our sites through our platform. And then our technology platform really is exceptional in helping to refine our processes and scale our processes across our sites and provide technology applications that create the efficiencies in our system, that create better capabilities for pre-screening, for identifying patients for clinical trials.
Dr. Fourment: So, Clinical Research Strategy Group (CRSG), the customers for CRSG are 1) the site that only wants to build research but doesn’t know how to get started, doesn’t want to take the time to build or figure out how to build the infrastructure. The second, customer in CRSG is the site that is already built and already running research but maybe wants to take it to the next level whether it is just increasing the profitability, increasing the geographic size, and scalability. But the key with that group is… to really provide for groups that want to do good research, the tools to build the infrastructure and allow them to be sustainable long-term on their own.
With Precision Research, Precision is called a centrally integrated research network or CERN and what this – it is a network of really good GI clinical research sites around the country who have shown a lot of performance in the past and who already do good research. And what Precision does is, it contracts with pharmaceutical companies who bring studies. And once we bring the study to the research network, then we handle a lot of the pain points for the sites. We handle a lot of things like the startup, we handle the contract, and we handle the budgeting, the regulatory (for instance) is all done for them. We build out the source documentation; we build out the study in the CTMS system or the Clinical Trials Management System. So, we do a lot of the heavy-lifting which allows the sites that are a part of Precision to do what they do the best, which is to identify patients for trials, and get them in, and see the patients.
Dr. Fourment’s background:
So, after medical school, I got an offer from a pharmaceutical company to come into their medical affairs division and I worked for seven years in IBD at the pharmaceutical level as a medical science liaison and liaison between clinical operations and medical affairs in the U.S. So, one of the things that, that allowed me to do is to see a bunch of clinical research happening across the country. And I saw sites both in academic and community practice and worked with those sites in clinical trials.
And what I noticed was that there were a lot of sites that were probably destined for failure in the next five years. In other words, the burden of doing research at their site was becoming so much that they weren’t going to be able to, kind of keep it going. And because of the burden and because of the pull of their regular practice the doctors probably at some point were going to have to make a choice, to decide whether or not they wanted to devote more time to this research effort or whether they just wanted to continue their practice.
I then went to work for TDDC, in the GI alliance and worked with a great partner, Dr. Tim Ritter over there. Where we, for five years built that program, to one of the premier GI clinical research programs in the U.S. And after that, I decided to really continue to do what I think I love doing which is helping sites become really good.
Research as an ancillary:
So, basic reasons I think to do research as an ancillary in the practice and to create an ancillary out of it are that it sort-of helps everyone. If you look at it from the patient standpoint, the patients have access to those therapeutic advancements that most won’t have access to for the next 10 years and they have access to them today through clinical research. So, it’s a great way to bring those things to patients sooner. What it does for patients who don’t have insurance, for instance, is a great option. It is a great way to be able to see patients more.
If you take IBD as an example you know, I think all of us believe that in the ideal world we would be able to see our patients sooner then, let’s say six months for a visit and with research you are able to do that. You are able to see your patience on a graduated scale to make sure that their disease is being aided by the approach that you’re using. It’s a better patient touch. So, that’s what it does for the patient. For the practice, you know, I think to our point it can certainly be an ancillary. You know we look at these research visits, and I think ideal to me in my mind is an average patient visit in research generating around $1700 to $1800 per visit. And when I look at how many visits a coordinator is ought to have over the course of a month generally speaking what a grade looks like for me somewhere between 20 to 30. So, if you multiply let’s say 20 visits by $1800 per visit you can see that if you have the patient in your practice, and you bring research into your practice, it doesn’t take long to really grow to a point where it can become a good ancillary. That’s the direct value for the practice.
The indirect value is that – not every practice has research and so the way you’re viewed in the community if you have a research program going on in your clinic may be much different than the gastroenterology practice down the street. And that could impact things like referrals as you get referrals in from the primary care. That could impact the way that the patient sort of views your practice if you have research. So, there’s both a direct and indirect value to having research in practice.
And then there’s the last part which is profit. So, if it helps the patient, and it helps the practice, does it help the bottom line? And you know, the way that research runs in a lot of cases in practice it’s kind of a break-even type of a prospect. But there’s a way to…in a method to really making research become profitable. So, if you like the first two pieces, if you believe that it helps the patient, if you believe that it helps both directly and indirectly to the practice, there is a way to get profitability.
Clinical Trials Management System:
One of the things that we rely on heavily is a Clinical Trials Management System it is sort of like an EMR for research and it allows a lot of transparency into the program. It also allows us to draw metrics from the program. One of the things that I see often in clinical research programs is if you ask the site how they’re doing in research. They’d say, “Oh we are doing phenomenally well!” Okay. So, how many visits are your coordinators having per month? “Uh…I don’t know, but they’re busy” is the answer that you will get. What we can do with the Clinical Trials Management System is to start to put some metrics in place so that the entire practice has an idea of how we really doing. So, in other words, how many visits are we conducting over the course of a month, how much per average visit are we getting? And that allows us to be able to go month over month, start to see trends. And so, in the practices that I work with, if we don’t have a CTM system in place, we would work to get one in place. So that, we can kind of draw on some of those metrics. That’s an important step. The other things that we do to get started are – we create SOPs (Standard Operating Procedures) that represent what the sponsors want to see out of research, and what the FDA wants to see out of the research. We create a corrective and preventative action plan or a CAPA plan. A CAPA plan is what we use whenever something goes wrong in research and we have a protocol deviation to make sure it doesn’t happen again.
Establishing a budget:
To establish a budget for the sites again based upon the actual value of the time that they’ll spend in studies and we put together justification letters so that when the sponsor comes back and says well we can’t give you X number for this particular procedure you say, ‘ Hey look that’s my policy here at the site’. It’s a holding type to some of the things that you know, are reasonable value for the practice is important. Not taking less than what you’re worth.
The role that we play at the site is more of a Co-directorship, right? So, we really partner with that site and I’m on calls multiple times a week with each of the sites that we work with to make sure that things are going in the right direction.
So, it is a cost involved, obviously. As with any ancillary, if you build an infusion center you’re going to have to buy infusion pumps, you are going to have to buy chairs, you are going to have to do all of that. For the equipment costs for what you need to do research – refrigerators, freezers, centrifuge, and things like that. The cost for all of those is around $15,000 per site so if you want to do multiple sites it’s going to be sort of amplified there. Again, the cost of the CTM system is nominal. And then CRSG can work in many different models. Either to help identify staff that practice could hire and or we are considering models where we could actually find the staff ourselves and so, depending upon what the practice wants to do, depending on what level of risk they are looking for, we can work within those constructs. And it is important to do it individually so rather than having just a sort of one-size-fits-all kind of a program, we’re able to look at what the site’s needs are and what the site’s desires are.
Now obviously, if they take on a lot of risks, they’re going to keep the majority of the profits in that case. We are taking on a lot of the risks, then the profit shifts to this side.
Types of trials:
So, there is a lot of IBD research, Crohn’s and Ulcerative Colitis, in both phase two and phase three. Phase two trials are the shorter-term studies and phase three are the longer-term studies sometimes out to seven years. So, there is a lot of work that really needs to be done that is on offer right now. There is also work going on the luminal side, and eosinophilic esophagitis, celiac disease, and many others. On the hepatology side, there are NASH trials. And I always recommend that sites should consider broadening out their scope.
By Praveen Suthrum, President & Co-Founder, NextServices.