Welcome to Farmer Talk Radio. I'm Andrew Goldstein. In this podcast, I'll be joined by raw Lima, SVP of Strategic Clinical Operations of Inception Group, about clinical trial rescue. In this conversation, we're going to address a scaffolding approach where chief medical officers of biotech companies can prioritize the areas that need immediate support without sacrificing the entirety of the trial and thereby safe time, money and energy rall. Why don't you introduce yourself.
Hi, my name is raw Lima. I'm the executive vice president of Clinical Operations for a company called Inception Group. I've got about twenty five years of experience in the industry, most of that as a VP of clinups for very small biotech sponsors.
To get us started, can you define what you mean when you talk about a rescue and what you mean when you talk about scaffolding.
Yeah, I know this one really touched a nerve at the CMO conference when we first started talking about it. What I'm really getting at with a rescue or when people historically and my experience talk about rescues, they're really talking about completely changing their vendor, right they're talking about ripping their study up, study out from the roots and almost starting fresh right. That is very much a nuclear option, and that is very expensive, very difficult operationally to pull
off without tanking the whole study. And so what I'm what I'm actually talking about is coming in and rescuing a study right doing what is in the word without going nuclear and the the or without I'm going to use a building analogy and we're going to beat this analogy up throughout this whole podcast. You don't have to demo the building to build a new building, right the way that we refab buildings in New York City and all,
we're not knocking everything down. We're putting up scaffolding and we're repairing it from the insides, and we're targeting what needs to be fixed. And so if you use that analogy that it really is the what I am talking about. It's it's putting some controls around what you do have and targeted fixing the things that you might need to fix. But what that really comes down to is identifying what needs to be fixed rather than focusing on the symptoms,
which are often bad enrollment. The costs are getting out of control. Those are the sorts of things that get people to say we need a rescue, but really identifying what is the problem and getting to the core issue so that you can keep what's good and fix what's wrong and support the greater infrastructure that is your study.
So how can biotechs better identify the root causes of these issues so that they're treating those rather than treating a symptom.
This is very much an art form and it is the million dollar question, right, But if there are going to be problems, they really come down to first you'll hear me. Start, there is a fundamental truth to the operational reality of your study. So sit down and map your study. Who are the vendors, Where is that information flowing right, Where does the information get collected, How does it flow into a database, How does it flow into your clinical database? Who is engaging with the patients? Right?
So really map your study out so that you understand how it works. And when I'm saying this, I'm really speaking to the executives, right, the chief medical offices, the CEOs. I'm assuming here that you have a clinops team who might have already done this, and if you don't, you should probably start there. And get one who can help
you with this. But very often, and I've had this experience being a lifelong clinops person, that very often that work gets done at the ground level but really doesn't get fed up into management in sort of the detail that it probably needs to be. Particularly when things are going wrong. What you end up getting is opinions of what is going wrong rather than sort of really trying to identify yourself. But the targets are you know, ultimately they come down to a few targets, the sites, right,
So are the sites able to execute the protocol? Are the patients able to execute the protocol? Right?
Like?
What is the burden you are putting on? And I don't mean theoretical burden in terms of, you know, this assessment takes fifteen minutes, this assessed assessment takes thirty minutes, But there's an there's a real burden that comes Sometimes those assessments aren't done in the same place in a hospital, and so if you stack them up, and sometimes if
you stack them up, it becomes very burdensome. And if you stack those things up with timeframes and they are done on opposite sides of a hospital campus, that is virtually impossible for sites to do, and that will will come out in things like protocol deviations. At best. At best, people will try and you will get failures. But what at worst what you see here is people don't do your protocol. They just say it's impossible and they quit
on you. And so having that discussion, and not just with the pis, but with the research nurses, the study coordinators, finding ways to touch other parts of the institutions so that you really understand what is going on. So that's the first is really understand how this is happening at sites. The second is, well, who's interacting with those sites and who's asking those questions? And very often, particularly small biotechs
will be very hands off with this. They hire a big cro they hire some contractors, and then they get hands off because they say it is their job. At the end of the day. That might be right, it is their job, but it is ultimately your responsibility and it is clearly when it goes wrong, your problem. So spend some energy there and do it yourself, or get very experienced people who you trust, know, maybe have experience with, have worked with before, and bring them in. And this
is what I'm talking about is scaffolding right? You may have hired somebody for it, but you don't have to fire them and hire somebody new. Maybe just get a targeted approach to go do things like talk to your sites. Maybe have a targeted approach of having an independent third party person come in and talk to both your clinical operations group and your vendors and figure out what's going wrong. The last piece or the second to last piece that
could be wrong. Is the vendors themselves right? So is their staffing appropriate or do they have the right kinds of people doing the work? Have you had a lot of turnover? Right? Those are sort of red flag signals.
And then the last really is in the contract. And so I've met again, I've been in experience of this where we as biotechs have done it to ourselves, where we put out an RFP, it came back, we didn't like the price, so we redlined it, and then it turns out we needed all of those things, and then that shows up later, right, And when that shows up later, we tend to be surprised by it, but it's very
often shouldn't be surprised by it. Really looking at that contract upfront, like being honest with yourself about what you really do need, and then keeping a documentation of what we've readlined so we're not surprised by it in the future. Keeping them in things like a risk log are important. Way is to sort of mitigate this in the future. I'm not saying don't readline. I'm not saying don't try
to be efficient, but just be honest with yourself. Be honest with your future self about some of the compromises you might have made, because it does make it easier to reckon with them and identify what those problems might be if you have a strong record of it. And
today it's never too late to do that activity. And so if your contract was written poorly two years ago, or maybe you're a new team on a failing study and you're trying to make that decision, today is a great day to start looking in the mirror and being honest about the contracts you have in front of you and what they do and do not include, and trying to reckon with that all at once, because it is
very painful to do it incrementally. That that is painful for the vendors, and it is painful for the sites. It is painful for the overall study. So getting at the sites, vendors, contracts are really the three and the last pillar, if we're going to beat the house metaphor, the last pillar is the protocol itself, right, So the protocol, the sites, the vendors themselves, and the contracts.
So I understand the contracts, and I understand the protocol. But you know, when you're talking about site burden, or you're talking about vendors who aren't educating off actively, or don't have the right staffing or have turnover, you know, why is the answer scaffolding rather than you know, a rescue and going to a different group to work.
With that the ultimate answer might be going to a different group. What you want to be able to do, though, is a soft landing, right, And so cutting across into a new organization that has all sorts of new rules and a new way of working might be a similar shock to the system as before. So what I'm actually recommending is putting up scaffolding to make sure you're solving
the right problem. Because, for example, if the problem is the protocol, but you think that it is the staff, and you go and you fire your cro and then you hire a new one that is a very costly and painful activity that ultimately won't get you anything because your actual real problem was the burden on the sites
from protocol assessments. And then the new CRO is going to come in and have very similar challenges and you might have very similar outcomes, and so if you're not identifying the right problem, then you can't actually solve for it. And sometimes what you have with for example, staffing issues, Let's say with cras, this is a very common one where you know a lot of the cras out in the field, particularly with larger organizations, don't have as much
experience the company. Those companies are built for scale and they have some lesser experience staff, and if the issue is with those, then finding ways to support those just firing those staff and putting a new inexperienced staff, you might not get the kinds of people you want with the next one, and you're going to have to train that new person, and so you could get into this cycle of finding where what you really need is somebody to do some oversight and education of those people which
may or may not exist inside of that CRO right because the CRO is never going to be an expert at your clinical trial. They're never going to be an expert at sort of the intricacies of your assessments and the way you want things done. They're just not right. They're not living your trials every day. Some of the boutique CROs do and engage differently, but the bigger ones don't.
Like they're there to check boxes and to do source stark verification and collect documents, right, They're not really there to live your study. And so have somebody there to live your study and to help them through their day, help them be more efficient. And that's a real value add that you can put inside of your organization who can go across your programs or across all of your sites and across all of your vendors to create that consistency.
And that really does look like your clinops group. But again people don't think of it this way. They think of that as extra staff that you don't need and that you can redline. But that is a function. If you separate everything into its little component pieces, then if there really is nobody to tie it all together, then
what you often get is disassociated pieces. And it's not that those pieces are wrong, they're not coming together the way you want, and that often is what I'm talking about with scaffolding, Like, don't fire the people at the bottom who are making the pieces and get new people to make pieces, because they're just going to make those pieces. You need something different.
So how can companies implement scaffolding effectively?
You know, there's a lot of ways to go about this. Some have an instinct to go internal, right, so just to hire some extra people internally to oversee those activities. What I would say to most CEOs and CFOs cmos out there is that clinops is a very very difficult job. That is, you know, forty percent skill and like sixty percent solving problems right that come up emergently, and the
more skilled people are prepared for those emergent problems. In order to do this well, you need somebody who's seen those problems before, who are prepared in have backup plans. It is a very hard job. Don't under resource it internally, right, Let's start there. Don't underresource it internally. There is a lot of information, there's a lot of data to look at. There's a lot that can go wrong, and when those things go wrong, you're already like two months too late
to solve them. And so you really need people there living and understanding it in order to engage it well. So everybody wants to keep it into a tight internal staff. Just have some slack in your systems so that you can handle what I call the unexpected, the expected unexpected problems. Right, things are going to go wrong, make sure you have slack in the system to cover that. Also, make sure
you have people who can talk at multiple levels to vendors. Right, So very often we biotechs are built with very very high level people in mind, and they have high science
and high technology at their forefront. But if you if you skip down a few levels, the people who are cras don't necessarily have that same sort of skill set, right, They're just there's they're not going to have that skill set because their job is to be broad bridging the gap to understanding sort of what is coming up from the field, like the complaints and the difficulties, and then what the science is saying and how to implement that. You need people who can bridge that gap and so
really focus on that. Those sorts of i'll call translation skill sets. It's not translations of language, it's translation of jargon that that you really you really need, and so you can find this potentially through consultants, through boutique CROs, through through internal hiring with the right sort of skill set approach, right, but be really mindful that you have different people with different levels of skill that all need to be communicated and messaged to, and that in and
of itself is a skill set. I'd also say this on this point that as technology has become more and more infused into what we do, many of people, many of the people who deliver that technology are technology companies, not clinical companies, and so you really need somebody to do And I'm not talking data management in the classic sense i am I'm literally here talking about programming in
IT and back end data in you know, architecture. You really need somebody who can speak that language as well, because you know, nowadays it is very common to have four, five, six, maybe even up to ten different data sets feeding your final analyzable data set. Getting all that information to be brought in and talk to each other is actually extraordinarily complex, and you really should have somebody dedicated to speaking that language, because if you don't, you will have problems tying the
information together, and that is very hard to unwind. Once it is built right, it's a lot easier to build it right. Kind of add on to it, do transfers. If you build it wrong and the transfers don't work, that can be very painful and that often doesn't show itself until you are trying to get data out and
it becomes a crisis. So really really focus on these points of translation, and don't underestimate both that they exist and that they are getting more and more complicated as the as sort of our industry fragments.
Seems like you're looking for unicorn here who can speak the technology, you can speak broad and speak the jargon. How do you find these people?
Well, I guess that's my sort of point is that it might not be It might not be a single person, and don't underestimate that it might need to be multiple people. And I get for small companies that that that may be difficult. But that's where I'm saying, borrow this from boutique CROs or from consulting companies. Get your one or two good clinops, people who know enough to kind of put their tendrils in and to really help to help
you as an organization speak the language. But then borrow some independent experience from just bringing in your vendors, right because they might ask questions that you don't really understand, but you might think you understand, and that's where you go wrong. So just borrow that and make sure you have sort of solutions for checking your instinct and then if something does go wrong, borrow more of it. And that's the scaffolding approach, right like early on, try to
infuse this into the way you build your program. But if it goes wrong and you're at a rescue and you need to scaffold, then go out and find independent people who are good at this particular problem that you need to solve, or the set of problems that you might need solve, and go and engage with that and start with fact finding and then move yourself up. As we talked about early on, Andrew, the answer might be fire. You know, the ultimate answer might be fire your cro
and demo and rebuild. I'm not saying it doesn't happen, but I'm saying that it should be a process to get you there. That's where scaffolding can help.
So to drill down a little bit, you know, if you're going to need to bring another vendor in any way you know are there time and cost savings is that you know you don't want to end up in a situation where you're firing all your cras and hiring a new batch of cras who and you're going to end up in the same situation, or you know where, where are the time and cost savings for switching the approach?
The goal is to identify your problems and target them so that you are not just blowing everything up, and so you're walking your way there smartly, right, like we are not demoing the building because we wanted to change an electrical plug. The time and cost savings come from not actually demoing the whole thing and so incrementally walking your way to solving the problem, to the solving the problems in front of you and making sure that you're solving the right problem is the smart way to go
about it. Right. It goes slow to be smart, but
being smart goes fast. Right. It's that sort of mindset, right like you might feel that that need to go do something, break something, and keep moving, But often what that does is it is it compounds the complexity and compounds the problems and makes it very difficult to continue to operate long term, right, and you don't want to tank everything and so identify and I would say, if you are are held bent on actually changing over your CRO, it does actually make sense to overlap your new CRO
and your old CRO, and you might want to do that in a staged approach, right, So bring in your new CRO's project manager and maybe CRA manager at first to really get a sense right and engage them as internal consultants and let them get a feel for the study and what they're going to need and make sure they really understand it before you pull the trigger and change everything that the sites see. So you might end up, like I said, you might end up in those same places.
It might cost you more in the short run, But the goal is to smooth out the operations, make things mean for your customers, and make make things organized on the back end right, so you don't have sheer chaos everywhere.
So at the cmosumm it this past year, Ken gets brought up and I think he's brought this up in years prior as well, that we're seeing more and more protocol amendments happening, which add more money to trials and add more time to trials and earlier in our conversation, you spoke about expected unexpected? Are these inevitable? Are these rescues in scaffiolding approaches inevitable based on the way that
we currently run clinical trials? You know, he's there that we could be doing from the beginning so that we don't have to do an amendment, so that we don't have to, you know, hire another group to watch over everything, or hire another internal person to watch over everything.
I don't have this data, but I'm gonna I do believe that some of these amendments are inevitable because what's driving particularly for biotechs, right, biotech aren't really in the phase three space. They're in the phase one phase two space largely, right. Some do move on, but by the time they move there, they themselves become more mature, their programs become more mature. So really what drives a lot of these amendments early on is phase one and phase
two research. And I think it has gotten worse over time because the medicines we are doing don't have clean and clear regulatory pathways. Right, we actually don't know what the answers are, and we don't really know what we are doing, and we're using phase one in phase two to learn and I don't mean this in a bad way. That is good science. That is exactly the way science
is supposed to work. It's that the propulsion of these personalized medicines out of pre clinical and into human it goes a lot faster than in the with small molecules. And so what you're seeing is we're sort of learning on the job, right and we're learning with diseases that aren't well studied in academia, right, Like they don't have
big data sets, so we don't know the answers. And so I do think that we have to expect that some amount of amending the protocol, some amount of what we think is good science, hits the wall of practicality. That's the site the protocol or site issue where it seems like it's a good idea to do this thing and then send them to do a scale and then send them to an MRI. But those two things happen in vastly different places inside of the inside of the institution.
So if you're really trying to do them at the same time, that takes inordinate amount of infrastructure for an institution and might not be possible in some institutions, and so those sorts of things that we could do in one site or two sites, but then as soon as we try to scale up even to five or eight sites start to become improbable, if not impossible. We have to amend the protocols, right, and we have to amend the way we engage with the science and we engage
with the operations, and so those things are inevitable. I would say, I would say this, start by building it in. If we know that this is true one big failure, that maybe it's a failure, maybe it's a reality of the financial constraints of a company. Right that start by building it in. We expect that there's going to like expect that there's going to be two or three amendments, and then suddenly you're not surprised by having two or three or four amendments. Right, The financial hit is less.
And so if you if you build knowing what happens in the real world, then these become less of a shock. I think where they become a problem is where we think we know the answers, we try to engage with it, or we read line contracts, we readline protocols right and
say no, no, no, this has to be in. This has to be in, and then they become unenrollable or the budgets are way you off, and then those things start to impact operations and then what managed, Like I said, management has the symptom problem right, well, the board doesn't like what is happening from a budget standpoint or an enrollment standpoint. We've got to change things. We've got to
rescue this trial. And you'll hear people start talking about rescues or you know, we're not getting what we want. And then again you really have to identify why. And sometimes you did it to yourself, and sometimes it's the protocol, and sometimes the vendors doing it to you. But if you solve the wrong problem, then you're just going to be five more months delayed.
Anything else that we didn't touch that you wanted to share with the with the audience.
My goal here is to really get people to be thinking about operations as a strategic partner rather than just a delivery partner. Bringing operations into the room where you're planning the science and planning the logistics and whiteboarding and nap getting a protocol all is a valuable project. It is a valuable prospect if you have the right person doing that, a high enough level operations person coming in
to do that. And then even once that is done and you have a cro and you have a group, what I would what I would say is, you know, listen to your listen to your consultants, and listen to the people who might not be science oriented, right so you know, get your program protocols in front of study coordinators. Really go and engage with those sorts of people because they're going to have a perspective that you you might not otherwise appreciate. And if you can cut that off early,
then you know you're doing better planning. Right. It's it's the same way that the industry has made a big push to bring in patient voices. We think about our patients as the ultimate customer of the drugs, which is true, but the ultimate customer of pro calls is sites. And you should really be thinking about the people who are executing the trial at the site level and infusing their voice as well about what is and is not doable.
Don't just listen to the pis. The pis the pis overview everything, and the pis know the science and they have a particular lens. Go talk to the nurses and go talk to the you know, drug infuses or the technicians ultrasound and MRI. You got to go talk to them and find out what is and is not possible. And you know there is a fundamental truth. So the earlier you find it out, the better you're planning is
going to be. Don't stick your head in the sands and really think about operations strategically, both at the beginning and when you're thinking about rescue like infuse that back in.
Thank you so much for your advice and expertise in the clinical operation space and for talking about scaffolding and rescuing and how we can better approach different issues that may come up in the clinical trial space. But where can people learn more? Connect with you.
If you wanted to reach out to me. I'm sure my information will be connected in this website. But I work for a company called Inception Group, and we are an outsourcing partner and we engage mostly with very very small biotechs, and so I know I've done a lot of this for small biotechs, So you know, just reach out to me personally or Inception Group and we can go from there.
Thank you so so much again and looking forward to speaking to you again soon. I hope you enjoyed the podcast you are listening to raw lima SVP of Strategic Clinical Operations at Inception Group, about new approaches the clinical trial rescue that can save time, money, and energy by better anticipating potential challenges and identifying root causes. For more information about Inception Group and their clinical operations and project
management services, please visit Inceptiongroup dot com. For more information about the Chief Medical Officer Summer three sixty editorials, podcasts, or webcasts, please visit CMO three sixty dot org