Trials with Maya Z

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Maya: Hello. Hello, it's Maya Z again and I'm here with Dan Sfera. Everyone knows who Dan Sfera is, I guess. I was joking just before we started the recording that his videos are part of our onboarding plan for people who don't know anything about clinical research. So yes, here we go, the star Dan Sfera. Thank you so much for making the time [00:01:00] and coming here today.

I won't say anything about you because there is so much to say about you, but yes, let's say that I'm also one of your fans. So, Dan, just briefly, can you introduce yourself?

Dan: Yeah, my name is Dan Sfera. I'm a fan of yours as well. I love seeing my fellow Europeans, you know, I'm European, born in Europe, US immigrant. Three years old site owner, lucky, and fortunate enough to be a site owner from a very young age and I've done a lot in between - CRA, and training. I still do training of people to be CRAs and CRCs, but I'm a site owner still.

And I may complain a lot because that's what gets views, but I'm very grateful for what I do.

Maya: That, that's very important because if you don't love what you do, then you're definitely in the wrong room.

Dan: I'd been doing something else a long time ago.

Maya: Yeah. So Dan, one of the reasons [00:02:00] I wanted to bring you to my podcast is because I'm huge, let's say my passion is how we can plan better clinical trials. What can we do to improve the process and then get better results thanks to that? And as I shared with you before, I know that clinical research associates are on the front end of running clinical trials and observing clinical trials progress, but I've never heard from, let's say, feasibility teams or even clinical operations to hear how they're involved in the clinical trial planning process.

So are they involved in the clinical trial planning process? Should they be involved or maybe they shouldn't? What do you think?

Dan: Okay, so, ideally, yes, they should be. Practically, I don't see how that's going to happen. The way they are burdened with so much work. They can't even handle their training on the protocol once it's up and then training the sites. [00:03:00] Ideally, you would need them, because in theory they're supposed to be the connection, the direct connection to the sponsor, to the site.

That question should include, uhm, taking that question further. Should you include study coordinators in the conversation, at the end of the day, those are the two main workhorses for a study - the CRC and the CRA, and that dynamic is very interesting. That's what makes this trial successful.

Now, 90% of the time, these two groups are just told what to do. That's it. We don't care what you think. This is the study. Very smart people made this study and you are to follow exactly as we have laid out and planned, or you'll be retrained until you do, or you'll be removed [00:04:00] from the process. I mean, that's the way it is.

As a coordinator at the site level as recently as yesterday, and when we're done with this video, later today, doing things, CRC tasks for the site, it's extremely important, because the way these studies are becoming unfeasible, not just for the coordinators, of course, the CRAs, but the patients, and there are a lot of reasons behind it.

Regulations are the ones you cannot argue, and that's fine. But there are plenty of other reasons that are not regulations, they're exploratory endpoints for sponsors. Instead of investing in another trial, they try to mash everything together into one study. So if they have a drug and the drug works for, [00:05:00] let's say, arthritis, but they think, " Okay, maybe, this drug also can work on the hormonal, the PAG access. Okay, I'm not going to get into detail, but PAG access as well. So we will plan this protocol. Of course, it's going to be for arthritis, like we're going to have all the endpoints, that's fine. But we're also going to throw in certain things that are not necessary for arthritis.

But we're going to throw in these other exploratory endpoints and we'll just make the site do it. They already have to draw blood, so let's just throw in four more tubes and add a specialty lab. So they are sending the tubes also to the central lab. But while we're at it, it's just the coordinator, they're not important.

Let's have them also send to this lab internationally, where each time they do it, they have to [00:06:00] fill out a customs form and they have to put dry eyes. And then if the results come back bad or below a certain threshold, they have to draw another lab. And then they do other things that have nothing to do at this point with their arthritis.

Maya: Do you think that the CRA would know that, honestly, I haven't worked with CRA so closely. The CRA doesn't care. Okay. So maybe we need to work closely with the coordinators because they will know what the burden is for them and how this impacts the study.

Is that what you're seeing?

Dan: Yes, but the thing is the sponsors don't want to know because they're going to do this. It's saving them hundreds of millions maybe to add these, to squeeze the juice out of the orange. All of it.

Maya: Hmm.

Dan: The shell, even the crust, the peel, until there's nothing left, and then maybe [00:07:00] even vomit it and do it again. That's how it is. It's cost-cutting. So, this whole thing of exploratory endpoints is something no one's discussing. And yeah, it's saving sponsors a lot of money. But when sites are complaining and sites are frustrated, and when we say clinical trials are getting harder, this is one of the main culprits.

And by the way, the patients suffer, because I have a patient who has to come back for a screening visit for a simple study - what should be "simple" - 10 tubes of blood for a screening visit, when they only need four.

Maya: Wow. Wow. Yeah, I can see myself in this situation saying: " No, that's insane. Why would you need that?" So, yeah, makes a lot of sense. I wonder if sites are not happy, [00:08:00] but the sites' communication goes through the CRAs, right? So wouldn't they complain to the CRA and then the CRA wouldn't then go back to the...?

Dan: I do. So let me tell you how this works at the site level, right? And I'm unique, because I'm a CRC that owns the site, so I can't fire myself, right? I'm not going to fire myself. Most CRCs, 99%, will never escalate these issues. So they're just going to talk to their CRA and their CRA is going to tell them, " Hey, I know, I know how this study is. It's tough. It's insane. I'm sorry. insane for me too. There's nothing we can do." The CRA is just a therapist at that point, " Hey, let's see how we can fix your issues." They're not changing, they're not there to change anything systemically.

That's not their role, nor does the CRA escalate it because then they're going to think, well, sponsors are going to think, "I don't want to do this."[00:09:00] They're going to find someone else. And there are plenty of people that are so eager to be CRAs that they'll find someone. So this is the problem. And yeah, you can argue some of these exploratory endpoints are also justified in safety.

But, to what extent? They take a little bit of truth and they run with it because it's an opportunity for them to see, "Okay, maybe, there's some data here that we can do another indication for this drug." So the coordinator has to deal with this. I talk to you, my CRA, about these things until I realized that it's not going to do anything. So I've already jumped to the CTM and I'm finding the CTM at the sponsor level, and I'm complaining to them and I'm asking them, " What's the rationale?" And I've determined these are the conclusions that I've received and I've talked to colleagues who are other CTMS at other sponsors. They tell me the truth. Robert Goldman is one. This is what they're doing. They're doing [00:10:00] exploratory endpoints. The studies don't have to be this difficult.

Maya: Yeah, from the scientific point of view, maybe it makes a lot of sense. Look, maybe it makes a lot of sense because with a limited budget, you can actually get more data and then that will help you run your business more efficiently, I guess. But I understand that there should be some sort of a limit to how much you can push. How much you can save yourself, the budget. And I wonder, at the end of the day, you think maybe you're saving some money by having just one trial and then having these extra endpoints collected, but at the same time if that prevents the clinical trial from being successful, aren't you losing money at the end of the day?

Dan: They're looking at it as it's going to be successful, and it's still cheaper. Even if the study takes longer to enroll, it's still cheaper than doing another study.

Maya: Got it. That's interesting. Okay. But we started speaking about sites. We started with the CRA, [00:11:00] but you made it clear how important the role of the site is. I wonder, actually, two questions. First, everyone knows that when feasibility is done, one of the ways to interact with sites and get them, let's say, availability for a particular clinical trial, they'll run a site survey, for example, a site questionnaire.

So during these questionnaires, are usually sites being asked about these extra endpoints? Or can you complain about it, for example, you've seen that before and you're just making sure that you don't have this in your clinical?

Dan: They'll give you hints like.

Maya: Uhhuh. Okay.

Dan: Like, they'll ask you, " Does your site have capabilities to do this, this, this, and that? And then you just say " Yes" or " No" to all those things. And you might wonder, " Okay, why are they asking?" Yes, okay, there's probably going to be an eye exam. Why is there an eye exam needed for this [00:12:00] indication?

There are probably some safety issues, which in this case, there are safety issues. Okay, but then, why are they asking? Regarding the labs, they don't ask you, because in the labs, you're just drawing tubes, so everybody has that capability. If you're drawing any basic CMP panel, you can draw tubes for specialty labs too, so you don't find out till later, usually right before the SIV, just in detail how complicated these labs are. So when I'm doing the survey, in my head I'm like, " This is a normal study, you know, just five minutes to draw the blood and then 20 minutes to process them." When we're getting trained for the SIV, we're like, " Whoa, wait a minute. If this happens, then we have to draw this one, and then if this one is, we have to ship it to three different places. Oh, wow. Well, now it just became an hour and a half, but okay, we [00:13:00] were already at SIV. We have to do it now." That's the way it works. And so it's not, the details are not in the feasibility. You might get hints. But you're not seeing the full picture.

Maya: Hmm. Does that happen also with diversity? Because, you know, diversity is a huge topic now, everyone expects that this will be mandatory actually, maybe it is mandatory. Maybe there is no clear definition yet of how it will work and what exactly FDA will require, but it is more or less mandatory now.

So, with diversity, do you see a similar picture, like with these [00:14:00] endpoints?

Dan: My site is on the border of Arizona and Mexico.

A lot of our population are Spanish-only speakers, our first two patients are Spanish-only.

We still do not have, despite the industry's push for diversity, and the reason they selected us is that at least half of our patients will be.

Maya: Yeah.

Dan: This is desperately needed because the FDA mandated it. Do you know, Maya, that we still do not have the Spanish informed consent?

Maya: How come you started the trial?

Dan: We have fancy technology for anything you can think of. We have air bills for four different places and customs forms. We have apps. We have things to remind us about everything that we don't even know about, and they want Latinos in the study, and we're [00:15:00] still waiting on a Spanish informed consent.

Maya: You know, what you're sharing now is exactly the reason why I started the podcast because I love being at these conferences, speaking with all sorts of leaders and, CEOs and, you know, innovators, disruptors, and so on. And at the end of the day, these everyday things remind us that we have to start much, much earlier to think about the basics.

If we are site-focused, patient-focused, or whatever, what does this mean? And you now gave me this example. If we want to have a diverse population joining the clinical trials, then we should better do our homework to invite these people, to make it easier for them to be a part of that.

And I guess that e-consent or whatever consent in Spanish shouldn't be a big deal, right? So, in this case, why is it [00:16:00] that you don't have consent? Do you think it's more like a process type of thing? It's because there are multiple stakeholders involved with that and nobody knows who owns what?

Dan: No money in it.

Maya: No money. Oh my God.

Dan: Where's the money? This is why I'm so jaded, like, all these disruptors, all these people with their hands out, " Hey, here's your problem." They invent a problem that doesn't even exist, " I have your solution here, CRO, give me the money." Translating informed consent doesn't require anything disruptive.

Maya: Yeah, of course.

Dan: But there's no money there either. It's just something they put, " Oh, well, we don't have it yet. The IRB didn't have a chance to review it. Our certified translator is not, they didn't do it yet." What do you mean? Spanish has spoken in almost 40% of the United [00:17:00] States households.

Maya: Hmm.

Dan: You cannot find a certified translator? I understand if it's some obscure language, but Spanish?

You can't find a certified translator to get it on time? Do you know what the sponsor told us? " We know you have a Spanish-speaking site. Just translate the English consent into Spanish." That's it. That's what they tell us and document it. So all these ideas and tech boils down to, " If I can't make money on it fast, the coordinator can deal with it."

Let's just give more to them. That's okay.

Maya: Yeah, yeah, I understand what you're saying. So, is there any way we can improve and make sure that what sites are experiencing and what patients are experiencing can go to the decision-makers' ears? How can we shorten that distance and make it work?

Dan: I think there's so much [00:18:00] between the sites who treat the patients and the sponsors who pay for everything.

Maya: Hmm.

Dan: 50% of the budget is wasted on the middlemen. And the middlemen are business. They're going to look at a high margin. Translating consent is not high-margin. That's a low-margin task.

Maya: Hmm.

Dan: It's not exciting, it's not going to be talked about at Scope. At Scope they're going to talk about e-eCOA or " Oh, let's enhance the patient journey with more apps because those cost money and CROs love it and CROs want to pay for it because they're going to impress the sponsors that they have the technology."

But at the end of the day, it's not more technology that we need.

Maya: Yeah, I agree. I have one hypothesis that if we relocate the [00:19:00] budget that we are bringing to enrollment assistance, the guys that help the investigator identify their eligible patients, for example, and relocate this budget to coordinators, I think we'll have better patient recruitment because I agree with you. If sites are engaged and happy and willing to collaborate on this clinical trial, and then if we provide meaningful clinical trials to patients and meaningful clinical trials that give them some value in one way or another, but also take into consideration what's normal and what's not normal. For example, we will be successful in patient recruitment one way or another, but if we just try to fix things with technology, what we are doing now, not just in clinical research, not just in this industry, but all industries, is just put some more technology. That's not going to happen.

That's not the only solution. I'm not saying that we don't need technology, don't get me wrong. We do.

Dan: Technology is great. I'm a huge fan. [00:20:00] Our site uses everything eSource, eReg, and eConsent. We use all of this stuff. The only old-fashioned thing is we give cash to patients, but everything else is the highest tech. Because it works, it does work. But at the end of the day, we don't need more. We don't need another app for a patient to log their diary when we don't have a Spanish informed consent and we don't need all these tools that they think are going to enhance the patient experience when it's just to get more data for the sponsors. When a sponsor pays for something to a vendor, they're asking, basically, " What do we get out of this money?"

And so it usually means more data and that comes at the expense of the patient having to be more burdened, actually not less.

Maya: Hmm. Yeah, I understand. Well, Dan, if there is one thing that you would like to change in the way [00:21:00] clinical trials are being planned, what would that be?

Dan: Well, I don't know because it's easy for me at the site level to say, " Hey, let's get less exploratory endpoints. It's getting ridiculous. But if I were at the sponsor level, it makes sense. It's like, " Yeah, why not?" So I think sites, myself included, by the way, this study I chose that I'm complaining about, I chose it, right? And I didn't realize it was that difficult when I chose it, but I chose it. Do you know why? Because we have a huge amount of patients in our community that would benefit from this study. That's why I chose it. I didn't choose it for money. Of course, I assumed it's gonna be a fair budget, and it is.

It's a good-paying study. So I'm not complaining about that. I'm not complaining about the budget. But I think the fact that sites are being ignored, especially coordinators. Coordinators are [00:22:00] the bottom of the totem and they're the ones doing - they and the CRA are doing everything like PI, just for safety and oversight.

But the CRA and the CRC are the workhorses and they don't have any voice. And I don't know how you give them a voice. That's meaningful. I could see them giving a voice to show that they're giving them a voice, but not doing anything. I honestly don't know how we can change it because I understand the incentives from the sponsor and then I understand the incentive from the site. We have to learn how to deal with these difficult studies because they still pay well and our patients could benefit from them.

Maya: Yeah.

Dan: I'm not sure if I would change anything.

Maya: Yeah. Well, Dan, you are right, and at the same time, I know of many colleagues of yours who just decided to quit and never do a clinical trial anymore. So I think that we just can't [00:23:00] agree that that's the status quo and that's it. We shouldn't change because we know the metrics. I don't know it off the top of my head, but the percentage of sites that do only one clinical trial, and then they quit. It's huge. And, in the US, for example, you have a lot of professional sites, but in Europe, for example, there are not that many. So that means that you're competing with the general practices of these doctors. Why would they do a clinical trial where they're challenged and they don't feel heard, for example?

So I think we should do something. I don't have a solution, but I hope that we'll find the solution one way or another.

Dan, thank you so much for accepting my invitation.

Dan: Thank you, Maya. This is great. We gotta do more.

Maya: Yes, we will. There are a lot of questions, but I'm pretty sure that even now, people who listen to them, will get some insights. I learned something new. So, thank you very much. [00:24:00] One thing that I love about you is that you're always transparent and speaking loud.

Many people don't and they just quit. And that's why we are here. But I hope that this will change. So thank you so much for doing what you're doing, Dan, and thank you so much for your time again today.

Dan: Thank you as well.