COLLABORATION FOR BETTER PATIENT CARE WITH CHRISTINA DIARCANGELO AND GUESTS
Christina: Hello everyone, and welcome to another episode of I Am Christina DiArcangelo. And today you'll notice that we have a lot of guests on because we have something very important that we want to talk about today, because each one of these guests that you see today and you hear have already been on my show and we've talked a little bit about this subject. But after talking to the three of you and then obviously being on Dan's podcast as well, I thought it might be a good idea for us to talk about patient enrollment, subject enrollment as it relates from a clinical trial site level. And today you'll see that we have United States on as a site level person with Dan. We have Poland and ten other bordering countries that Anna is here to talk about. She's here from Poland, and then we have Pathik who's here from India. So I am so honored to have all of you guys on today. Thank you for joining me.
Pathik: Thank you. It's our honor.
Anna: Thank you very much for the invitation.
Dan: Thanks for having me.
Christina: Thank you. So where do we want to get started? What is it that kind of annoys you from a site level as it relates to when you get a protocol and you're expected to operationalize it? What are some of the things that are aggravating for you that you think we can do better from an industry perspective and then we can just kind of go from there if that sounds good for you all.
Dan: Sure. I don't want to hog up all the space, but I can go on forever. Let's start with the inclusion exclusion criteria of these studies. They are unrealistic and increasingly so since I started in 2005. I noticed a huge increase in complexity that's largely due to exploratory endpoints, I believe, and unrealistic expectations of these protocols written by scientists and MPHs and whoever else is writing these things, and probably ivory towers that are never connected, maybe never treated a patient in their lives. And then having us, expecting us to find these patients just out in the doctor's offices, which rarely they don't exist. So that's like where I would start with my biggest complaint. I understand why it's done. Well, to some extent, I understand why it's done, but that's been my biggest complaint by far.
Christina: Thank you, Dan. I can definitely understand your perspective on this topic because we've talked about it before. I've been responsible as a CRO to run studies that are of this caliber, where even I'm wondering, well, how are we going to find these people, right? It's like trying to find a pink panda bear in New Jersey. They don't exist, right? Everybody knows that there isn't a pink panda bear, right? It doesn't matter where geographically you're sitting, there's no pink panda bear unless it's a cartoon. And I find that, in my opinion, some of these things that I've seen as far as the developments of these inclusion, exclusion criterias because most of my time I've spent sitting in the sponsor side rather than being on the CRO side. That didn't start until 2010, really, technically. But I get hired a lot to come back in house and fix problems when they don't enroll trials properly which all stems back to how they design the trial to begin with and what their inclusion exclusion criteria is. Anna, Pathik, what are your feelings on this inclusion, exclusion criteria issue? And if you can also bring up something that you find aggravating, I would really appreciate it if it's different than inclusion, exclusion.
Anna: I may add few comments here from my side. I am a medical professional from my background and I am starting my career in clinical research as a sub investigator and working together with research teams and looking at these criteria and protocols like medics. And of course, sometimes it really looks weird when you see some of the criteria that cannot be combined altogether in one patient, when it should be all together in one person, in one organism, as whole bucket of these diseases that the person always have here. But as we usually said, and in our industry, now we're speaking that we need to listen we need to listen to our patient's voice. And as I know that the last version of GCP, it is now also has some of these new notes about engagement of patient groups, patient advocacy into the development of protocols. Perhaps we're coming now to this stage when finally the patient's voice will be heard and understood from the industry as we have now. It's written in some way in this main document of our industry and in our clinical research trials as well. So, yeah, I fully support this idea regarding the inclusion exclusion criteria. And sometimes maybe we have some misunderstanding of the procedures because they sometimes created this protocol scheme of procedures in such a way that it's not possible to convince patients to participate in a clinical trial just to follow all of this procedure. That seems weird for them and medical professionals with this frequency, with some specific amount of blood or something else that should be, for example, IMR that should be performed with some frequency that is weird. And this sometimes is the burden for our patients to agree to participate in clinical researches, even having all of these inclusion exclusion criterias in place.
Christina: I think sometimes as the sponsors develop the protocols, they don't look at the amount of time they expect these patients to your point, Anna, to be there at the site. Some of these studies I've worked on in my career, especially oncology studies, my god, the patients there 9 hours, they're already sick, right, and they don't feel well and they don't want to really be there. But this is their last hope, right, to participate in this clinical study in some patients minds, right? Especially if the disease state is really bad. So if they're going to sit there for 8 or 9 hours. If they're able to still work, they're taking time off of work. If they can't drive, they have to then depend on someone to either pick them up and take them. Or maybe the sponsor allows a stipend for a taxi or Lyft or whatever type of transportation is allowed in your country. So I completely agree with you. And when I have my advocacy hat on, which is separate than my clinical research hat, these are the things that we try to advise our sponsors on, is listen, they're not going to sit there for 9 hours and they need to eat something also. Like, what are you going to do about that? Pathik, your thoughts?
Pathik: Yeah, no, I completely agree with whatever's said. Sometimes we work with global pharma and there's one protocol across the world, and many times in India we have different genetic makeup, everything's different. So there has to be a little bit tweaks allowed to the protocol, which if our IRV brings it up, it generally doesn't get passed. The other thing which Dan brought up is about complexity, increasing and unrealistic expectations. I can remember an instance where we were working with a global pharma company and for some reason it was a competitive enrollment, very tight timelines. We had to do 10 patients in 3 months for an RA study. And in the first month I get a call from the VP saying, what's going on? You've only enrolled 3 patients so far. There's this other site which has done 12 patients. Where are you guys? And at the end of 3 months we did enroll 9. We couldn't do the whole 10, and the other site did 25. But you won't believe this. About a couple of months later, the VP calls me back and said there were enrollment issues with that site and 19 of them were non evaluable subjects. But your 9 were all perfectly good subjects. So sometimes the expectations are just unrealistic. And I'm glad this guy actually was gentlemenly enough to call back, but this doesn't happen very often.
Christina: No, it doesn't. And I don't know about you guys, but since we've been stuck in COVID, right, since 2020, and we've been operating clinical studies in COVID, right? And we've had to do things differently to get the patients to come into the sites because they're afraid because of COVID. Right? Then we had patients who got COVID and we have all the patients that took the vaccines. Right? So now our patient population is corrupted. How are you going to find, so the reason why I'm bringing this up is one of my clients in particular that I worked with for 2 and a half years, they were running 4 phase 3 studies at the same time in a neurological disorder. I won't say exactly, because you guys know I can't. However, I had cautioned them in the beginning. It was '21, fall of 2021 when we were kicking the first phase 3 off and then all the other ones were coming behind, I said listen, you've got to focus on the COVID aspect, not just from a retainment or trying to get the patients to come into the clinical program. But you've got to think about what these patients now look like, if they have the vaccine, if they had COVID, do they have long hauler syndrome? Because that is going to impact your study to the maximum capacity. Guess what? Fast forward to last year. It was ironically, my dad's death anniversary. That's why I can remember in my crazy mind and they, this company, publicly traded, had to release a press release that they bombed the first phase three. Then the other phase three was following suit. All these they were all blowing up, right? And so they tapped me and said, can you come back in and look and see what you think is wrong? First thing I said was, who did you enroll in this study? Did you allow long haulers to come in? Did you allow the vaxers to come in? Did anybody get COVID while they were on your study as well? That was the first thing I said. And guess what? I was right. That's why their studies bombed. They enrolled the wrong patients.
Dan: Yeah, and just wait until the next opportunity is going to be creating treatments for vaccine injured and long COVID, however you differentiate between those two. Maybe we'll get banned from YouTube for discussing this, but one of the things I wanted to bring up was I forgot who said this quote, but we already live in the future. It's just not evenly distributed. So I think in 5, 10 years, maybe sooner, we're going to have patient leads coming to us from our studies, like passively. I'm on a study now where the sponsor it's incredibly complex. 55 exclusion criteria, 55. The patients have to do all kinds of things. We have to jump through all kinds of hoops, like we're acrobats. But the sponsor hired this very good tech vendor that is a patient recruiter. And we've been getting, I'm telling you, lots of leads. They saved our study. But that's because our coordinators are calling. There's many sites, the majority of sites, they don't have time to follow up with the leads. So you're almost creating new problems because now you already have busy sites, now you're giving them all these leads. The sites are not interested to pursue these leads because that's a lot of work and the study is difficult. They're going to screen fail anyways. Why bother calling 50 people when only one maybe will get in? When I have an easier study, maybe I can enroll like two more in that time. So we have patient leads now. I think in 5 to 10 years with AI and with all these electronic medical records being integrated, the leads are going to be there, but it's going to require a new role at the site to persuade patients to do studies. And that's a full time job. And I don't think it's going to be the coordinators being able to do it because the coordinators have plenty of work as it is. Now you're adding another full time job to it. So the future is already here. It's just not evenly distributed. And we got to start thinking about how we're going to respond to that because it's a good thing to get all these leads. But we haven't cleaned up our problems from before, so we're just adding more tasks for coordinators to do.
Christina: It's ironic that you brought this up. I swear to god, you guys, this wasn't something we rehearsed before we got on. But this is why APA opened up the wing to start recruitment to help sponsors. Right? The last study that we sat on, which all the press came out when we were successful and we met our endpoints and decreased pain 77% after day 90, that was pretty huge. Right. What we did was we had the electronic capacity through Spectral because we have bots that can help find patients, right? And we have Cannabot and Dr. Bot that talk to patients and pre screen. So what would happen is we would get a hot lead to APA. APA then would spend almost an hour on the phone with these patients because you guys get it why it would take about an hour? Because we're trying to listen for things they don't necessarily know to tell you. These are uneducated people. They don't work in this space. Right? It's our jobs to help provide them with education and comfort in this process without looking like we're trying to force them to come into a clinical trial and violate their rights. Right? So what we did with that was APA would have the schedules for the sites. So if we had people that were ready to come in after we did our next round of discussions, they got scheduled immediately into the clinical trial sites. The study coordinator didn't have to do anything. Now, once they got to you, now you have to do your job, right? And you've got to reschedule them back in and all that good stuff. But we gave everything to you hot and everybody was scheduled in for you. It was like a concierge.
Dan: That's the future. Yeah, that's the future.
Pathik: That is the future. I completely agree. It's great that it enables, technology enables. But the life of the clinical research coordinator is really hard, I would say, because they have to deal with so many stakeholders, whether it's the principal investigator, the site director in the site, the monitors, the IRB at times. So they're just juggling a lot of balls in the air and still they have to keep the rapport with the patient really good so that the patient comes back and reports if they're facing any issues. I think the study coordinator is really critical. Unfortunately, the CRC has never given so much importance or due in the whole clinical research landscape, I guess.
Dan: Yeah, CRO role will be limited in the future, I think at least the CROs that we know, it the top 5 or however many there are after the mergers. But yeah, that'll be different.
Anna: Yeah and that's why they're coming to these decentralized clinical trials, that this will be the future as well and will be the combination. I agree with all of you with some of this approach in patient recruitment, in patient engagement activities, because in any case, it should be the delegation of responsibilities. Otherwise none of the research members, research team members will be not able to perform with a high quality, with a high speed their duties. So this should be this delegation and of course the separate work with patients and especially maybe for this decentralized, more remote activities, more remote work that will simplify the operation inside research team and with patient community as well.
Christina: Yeah, I think the technology aspect, what we've learned in COVID is that we need to make sure our technology is bumping, right. That we're helping these patients because when we can't find the patients because we don't know what's wrong with them because of something that happened to them medically, that's a problem. Right? And then the patients that have to stay on until they die, those poor people. I remember working on those kinds of studies and you didn't know if the person was alive or dead. Right? Half the time you're waiting to figure out from the site if they know what happened to subject 29 and if they're still here or not. Technology is definitely going to make sure that a lot of these needs are met for the patients.
Dan: Yeah, the delegation will change too, because at what point do we put technology on the delegation log or whoever's managing the technology? Maybe, I suppose, but at some point in the maybe not too distant future, it's the technology itself that's going to be on the DOA log. So it's just a matter of time, I think.
Pathik: Yeah. We started off with a decentralized piece during COVID and I'd be honest with you, we did face a lot of issues initially. There were pushback even from the investigators, some patients as well. So it wasn't easy with technology. But I think we are slowly getting over that and we are over those challenges. So I agree, technology is going to be one of the key components in clinical research going forward.
Christina: And it's been interesting. I don't know if you guys are seeing this, but I know that we're seeing this on our side, that now, because of what happened with COVID and trying to keep these patients engaged with you and all these things, people are now building mobile clinical research units that they actually go out to the actual patient. They can pull the blood because they have an ER room. They basically built in an ambo. And this is how now they're reaching to their patients. And I think that's really smart, especially in populations where to Dan, where he is, this kind of thing would be a great idea. Because now you can go to the patient, you can see them, you can do what you need to do. You have your chain of custody, and you go to the next one after you get that one done.
Dan: Oh, yeah, absolutely. And also like things like getting medical records and getting the data, the more accurate data. So watch what happens when we're able to get the data more accurately from EMRs, from patients that are no longer self reporting on forms, but you're getting the actual medical records from the providers. And look what happens to the recruitment rates when you're no longer putting patients in based on their self reported medications and medical history. You're going to start excluding way more people. So tech is going to help a lot, but it's also going to make things a lot more difficult when it comes to recruitment and randomization. Most importantly, screenfill rates will increase.
Christina: I agree with you, because when I was talking about the other study that failed because they recruited the wrong people, when patients would come into the actual clinical trial site, from the beginning, it was up to the patients to tell the doctor whether or not he or she had that ailment. They're not doctors, and especially if it's mental health. Right? Your chips are already stacked against you as a clinical trial site. Right. You've got to believe with what the patient says. But sometimes they've forgotten what they've said 2 minutes ago, right. Because they have brain fog or whatever else is going on with them. So it's very hard to work in those types of TAs, therapeutic areas when you're in the space where you have to listen to the patient and you don't have access fully to the EMR.
Dan: Yeah, absolutely. We have one of my sponsors for my podcast, Creo, they're rolling out a product very soon. In the United States, 90% of the electronic medical records are the same 5 providers, and they've got a deal with all of them to where once the patient signs the consent form and the authorization to release medical records is included, the site doesn't have to do anything. The records from this patient, no matter where they are seen, automatically appear in the source. It's done. So imagine going through 3 hour pre-screenings and screening and then getting the consent form, only to find out, oh, wait a minute, the record says something different than what patient told me. I got a screen file now, so good luck with this, guys.
Christina: It's true. It's true. Everybody's agreeing, right? This is what happens in political research. And then US sites try to explain to the sponsor, these are the things that are happening. These are the patients we saw. These are the patients we had to kick out for all these reasons. You're always under the gun to prove that you're doing what you're supposed to be doing, when it should be like a peanut butter and jelly approach. We're in this together, right? So if a site tells you, or your sites tell you that there's a problem and that they're seeing this, you should be paying attention to those trends and make a change, because you're not going to be successful.
Dan: They often don't want to. I mean, in the case of the small biotechs, they have investors that are waiting for the quarterly reports. In the case of the large pharmas, they're stubborn and willing to wait until they get the patients they need, fit the round peg into the square hole, and they're willing to just add more sites and open up sites everywhere else in India and Poland and Mexico and wherever else until they get it. I think the life of a site is going to get a lot more difficult. The trials are going to get more expensive and I don't think they're going to change the inclusion, exclusion criteria. So, yeah, it's going to be a different industry here by 2030.
Pathik: I'm certain it's going to be. Yeah.
Christina: I would agree.
Anna: But at the same time we should remember I don't know how it's in the US. But in Europe, if we are speaking about decentralized clinical researches and all of these mobile units, clinical research units, the European regulations and legislation is not ready for such a huge wave of this approach in clinical research because I'm now working more with European sites in different countries and we have this decentralized approach and few studies that are going to start and we see a lot of problems on the regulation level with ethical committees, with everything that is going to be done smoothly and quickly. But it's also a huge button to continue and to start this type of clinical researches. Perhaps it will come. I know that it's more common in the UK, in the United States, but Europe is not ready to start such type of activities. What is the future?
Dan: Either here in the US. I mean, you have tech vendors that make the technology transfer simpler, but you have massive failures of decentralized clinical trial sites like CVS Health. They're no longer interested in doing research. They thought it was something easy. Hey, we have a lot of patients I don't know how many patients CVS has in their database, probably several hundred million. They have all the leads they can get any patient they want, but they found it very difficult and not worth their time. Same thing with Care Access, where they tried research on a bus, having a bus drive around and screen patients in underserved communities. That didn't work well. Pfizer lost billions of dollars investing in them or on a vaccine trial for something, I think for Lyme disease. So technology is going to facilitate transfer of the data, but the work is going to be continued to be done at the centralized sites. So I don't think DCT, the way the investors are talking about it on LinkedIn, is going to be here. Like, we'll have elements of it. The tools, Care Access failed. CVS health failed. But the tools they used will work. But it'll be small sites like me using these tools at a fraction of the cost that they paid for. Maybe we'll even get it for free. Sponsor will just say, hey, use this tool. Here you go. Here's more work for you.
Pathik: Yeah. So in India, we did it a little differently. What we did is we didn't have mobile clinical trial units. What we did is we tied up with, say, large diagnostic chains to go and collect the blood. We tied up with the big logistic company like FedEx to actually ship IP, and then somebody from the site would go to the patient's house to administer or to take history or whatever. So that's the way we managed. We got in the right players to do it. And it wasn't not like CVS or this bus company who just got on the bus to try and do the whole visit. But I think I agree with Dan's point that it's going to be the smaller, intuitive sites who know the business, who are going to survive. And, yeah, you've got to have brick and mortar at the end of the day.
Dan: That bus got a metaphorical flat tire and maybe a literal flat tire.
Christina: I remember one time I was working on a treatment in the DR, the Dominican, and we were meeting with the authorities. So we obviously, I stayed in the United States for this because we're in the middle of COVID and our lead principal investigator was on a bus going somewhere. I don't know exactly where he was going, but he had taken the call, like the Zoom on the bus. And I'm like, what is going on? You knew that we were going to be on this Zoom. Why are you on a bus? Who's going to listen to you if you're on a bus? I can't even hear what you're saying. There's all this background noise. When you brought the bus up, I went back to the DR, and I was horrified. And then, you guys know I make faces, right? So I'm trying not to because we're on camera. So I'm, like, trying to be like.
Dan: Well, and that brings up another issue. Like, if you take a bus into an underserved community, even in the United States, they're not used to. There's places in the US. Where there's no health care. So if a bus comes in doing a study, I imagine in India, it's the same in Africa and in Europe. If a bus comes through a village, okay, US, Mexico, India, I don't care where if a bus rolls through a village with doctors on it or people wearing white lab coats? Not doctors maybe. They're going to think that's health care. They're not going to think that's research. And who has the incentive to tell them, well wait a minute, this is not health care. Nobody's going to tell them that because you're going to have a line around the corner waiting to get in that bus. So what's informed consent going to be like and how do we prevent coercion? I don't see how this is going to occur ethically. I think this is going to blow up in people's faces if they continue to pursue it.
Christina: All they need is one patient to call because their rights were violated and it's because of the way that they were handling it and conducting themselves.
Dan: Or someone to get hurt. I mean look at what happened in maybe, you know Pathik in the 90s or early 2000s, right. Where these doctors went to villages in India and didn't consent patients. They just put them in studies but told them it's medical care and then the Indian government shut that down.
Pathik: Yeah, that's happened. Yeah. There's black sheep in the industry everywhere.
Dan: What difference is it if we call it DCT because we have mobile phones and computers on the bus and satellites on the bus like it's the same thing happening.
Christina: Right. Well guys, we're at the end of our time already. It flies by when you're having fun, doesn't it? So I want to thank you all for being on with me today and I think this is something that we should continue to talk about. Site level issues. I'd be happy to keep doing these things because I think it's important that the industry sees that the same issues, regardless of where you are located geographically, they're all having the same issues. So why is that and what can you do better?
Dan: We just need to network more with each other and prevent this nonsense from taking a hold of our industry. I think the small companies are the new big. And if you want to talk about decentralization, we should talk about small sites, small business owners, like all of us here, connecting that's decentralized trials, not some AI that's going to go on a bus and enroll people in a research study where they think it's treatment and other kinds of nonsense.
Anna: We are all in one boat. We are all together. Our patients, research site CRO and sponsor. In any case, from all of our activities will depend the outcome of our mission and industry, what we are doing and why we start to do this.
Christina: Thats Right. Why are we doing it? What is our why? Our why is to help people feel better safely. Don't break any laws in doing it.
Dan: Be a human being. saveoursites.com Everybody should check it out.
Christina: Yeah, no you're right. Well thank you all for being on today. I really, really appreciate it. And as always we say. Remember we are the same. I am Christina DiArcangelo.
Thank you for joining.