Trials with Maya Z

Maya TrialHub (00:00)
Hello everyone. this is Maya. with Trials with Maya Z and I'm with Dan Sfera. Dan doesn't need any introduction, if you ask me. But for the sake of following the tradition, Dan

I would say a dear friend of mine, someone that I follow since the very beginning of my clinical research career. And I'm pretty sure that a lot of you listening today are following Dan Sfera as well. He's the founder of Clinical Trials Guru has been part of sites, clinical research organizations, biotech initiatives, all sorts of things. And when I started my mini series on the importance of Standard of Care in clinical research,

Dan was one of the first people I decided to invite because, actually exactly because of that, because Dan has been a part of almost every single role in the clinical research universe and can contribute to a very diverse and very interesting, like with very interesting perspective. Like we were discussing beforehand, Dan, you have this big picture understanding.

of how the different stakeholders work together and what are the missing pieces between them. Thank you, Dan, for agreeing to once again join me in the conversation. Welcome once again,

Dan Sfera (01:23)
Thank you, Maya, and congrats on all your success. It's actually amazing what you've been doing. Been following you since you started, I think. Yeah, 2016, you said. That's when we first met.

Maya TrialHub (01:36)
See, I'm good student.

Dan Sfera (01:38)
No, it's amazing. We need solutions to these problems made by real people, not necessarily by institutions.

Maya TrialHub (01:47)
Yeah, well, I always admired institutions and all the big initiatives they start, but I also see that they can't fill in the gaps across the board everywhere. And sometimes we as individuals, in our challenges and individual pathways and careers, we come across problems and issues that open our eyes

It's up to us to actually whether we will take the challenge or not. And as I mentioned to you earlier, one of the challenges that I saw lately is the fact that the industry, like our clinical research industry, doesn't necessarily understand that there is such a big difference between how people are treated country by country, region by region, and implementing the patient voice, something that we preach for so many years.

But I like to say I'm a pragmatic person. And when you tell me implementing the patient voice, honestly, I don't understand what this actually means. How do you actually do that? I know that there so many people doing that for a living. But then again, I know it's super complicated. But what I understand for sure in a practical aspect is that not implementing the patient journey in the clinical trial comes with real, real challenges.

down the road once you start your clinical trial. I was mentioning to you that throughout the years with FindMeCure, we've supported millions of patients out there. And I saw firsthand how patients are deciding whether they're to go for a clinical trial or they will stay the normal standard course of the available treatments according to their either insurance coverage or let's say

their country covers. And I just saw how important it is for the clinical trial to understand these patients upfront so that they can maximize their chances on either getting these patients aboard, but not only getting them involved, also making sure that they will stay in a clinical trial. But then you've been a patient coordinator. You've been managing sites. Also now being a part of clinical research organizations, you have way more, even more

let's say, even more direct conversations with patients. Tell me, how do you see, how do patients actually make these decisions on whether they start, like whether they should join a clinical trial and how do they compare that, like how do they compare their clinical trial options, option with their otherwise like options, Standard of Care options?

Dan Sfera (04:35)
A couple of ways so majority referred by a clinician However, and I'm speaking from my anecdotal experience with my sites Advertising so if the site runs ads and they do a decent job of Raising interest not awareness people usually get curious and

Maya TrialHub (04:53)
Mm -hmm.

Dan Sfera (05:04)
Now the people clicking, they're two cohorts. They're either people, because remember these cohort now from recruitment is not people that have been referred. They're referring themselves. It's a different mindset. It's either they've fed up with their current treatment as is, and they're not going to wait for a doctor to tell them to do something. They're going to take their health in their own hands and look, or they're just curious. Like, what is this? This is interesting.

Maya TrialHub (05:15)
Mmm.

Dan Sfera (05:34)
those are generally the two camps of patients I've seen when it comes to following up on advertising or following up on like a social media recruitment. now that's a much smaller cohort than the ones referred by the physicians, but they're all people at the end of the day. And matter of fact, like some of them there's overlap, some get referred by their doctor and they say that, I'll think about

Maya TrialHub (06:01)
Hmm.

Dan Sfera (06:03)
And then they actually see our ad and they reminds them, you know, my doctor actually told me to look into this. So here they are. they're either, like I said, fed up with the current treatment, whether it's their doctor or the outcomes they're getting, or they're curious, as to new stuff or both. It's very rare that it's a moneymaking.

Maya TrialHub (06:27)
Mmm.

Dan Sfera (06:32)
endeavor, although there are some where they're looking to get paid and that's the primary motive, but that's in my experience the minority of cases, at least for the majority of therapeutic areas. So these are just real patients.

Maya TrialHub (06:47)
It's very interesting what you mentioned, Dan. Yeah, it's very interesting what you mentioned, Dan, because I do get a lot of questions. When I speak with someone that's not from our industry, for example, and they're just generally interested why patients are joining trials, the first thing they say is, do people join because they're getting paid for that? Like they always think that it's because of the money. But actually, I agree with you, Dan, that the people that I've met, like who...

actually volunteer for clinical trials, it's rarely the money. They don't even think about it. They even raise money from friends and family so that they can be a part of a clinical trial, which is another story. And they shouldn't have to do that. But sometimes they need to. I wonder, what are the expectations of these people? Especially the ones that see the, because let's say the ones that are referred by a clinician, let's say they have the conversation with their clinician.

Dan Sfera (07:27)
Yeah.

Maya TrialHub (07:46)
but the ones that see the advertisement and they straight come to the site. What are their expectations when asking for the clinical trial and what are the things that are truly important for them?

Dan Sfera (07:56)
90 this is why I think we can do so much better The vast majority I would say 80 to 90 percent think it's a scam But they still want to come in and see what's going on So as long as you the admin I call it the admin the person scheduling their visit behaves like a good human being

has a conversation with them, maybe raises some early awareness of what research is. They come in a little bit less guarded, but they're still skeptical when they come in. Like, what do mean you guys are going to pay me? Like what do have to do? They're very skeptical, especially Hispanics. I'm in the Hispanic community here and it's extremely laced with a lot of skepticism, probably stemming back

the culture and Latin American countries where, you know, maybe there's less ethical considerations for patients or less of these kinds of discussions. At least in the past, I know Latin America has made great strides in a lot of their countries as far as research, Mexico, Colombia, Argentina, to name a few. But they come in skeptical and then it boils down to the coordinator and how they make them feel.

And we will have patients like a small percentage less than five leave. come in but they don't sign the consent. Probably less than five. It might even be less than two. It's so rare that it's actually memorable when they do because it's not common. But that tells me the patients are afraid of something. you know usually the ones that leave are

Maya TrialHub (09:30)
Mmm.

Dan Sfera (09:48)
Physician up. They're not patients of the PI. They're from outside our network and They're looking they're desperate enough to look for Treatments in what they consider weird places But they're afraid and that shows me that the journey starts with awareness really I mean if you are afraid and You still show

Maya TrialHub (09:52)
Mm

Hmm.

Dan Sfera (10:17)
someplace that you don't know anything about. Like that should tell you what the health situation is for that person. Like why would you, if I'm afraid, I'm not going somewhere unless I'm really desperate and need some changes in my life, right? So you're seeing these people coming in. Now, thankfully the majority of them end up staying and have good experiences. Even if the study drug

doesn't work for them. As long as they're treated well, they're willing to do more trials because they understand. then the referral rate from them is super high. So that's how you could measure the site's success is how many referrals are you getting from the patients themselves? Because that's the best form of advertising right there is getting the patient to refer friends, family of theirs. That works much better than any advertising.

You can't pay for that kind of referral, honestly.

Maya TrialHub (11:19)
Hmm, yeah, I guess in the center is a trust and that's maybe the reason why people who are referred by either friends or their clinicians are way more confident this is the right choice, the right, let's say, option where when you just like see an advertisement, like you just simply don't know what's behind that. And I

You just reminded me, actually, a few years ago, my team was supporting something like a stress test of a protocol draft. And we were comparing the Standard of Care between Germany, the United States, and one more country. I forgot which other country was that. And I was looking at the medical guidelines, the United States versus Germany. I think it was an oncological disease. I think it was Glioblastoma

And it was very interesting to see that in the medical guideline, the clinical trial, because Glioblastoma in general is a very severe indication. People don't have many options in their, like, let's say in the standard let's say in the Standard of Care, not many options. Also, usually this disease progresses very fast. So the percentage of people passing away is pretty high, unfortunately.

The bottom line that medical guidelines in the States were having a clinical trial as an option as part of the guidelines. But in Germany, that wasn't the case. And it was very interesting to see that these guidelines are followed by doctors at the end of the day. So the problem with the US guidelines was that it says, let's say, third line treatment, like repeating the second line treatment. It didn't work, but you repeat it with the hope it will eventually work. Obviously,

It's maybe pointless, but let's say for some people, maybe it will be a miracle. A miracle will happen and suddenly the second line treatment will work if you apply it once again. Or a clinical trial, but there is nowhere pointed out where you can find this clinical trial and what clinical trial you can probably refer to. even though, let's say, mean, yes, doctors are smart. They know that they can go to CT .gov. But then again, how many doctors really have this opportunity?

and the percentage of doctors involved in clinical trials is also not that high. But in Germany, that was not even an option. It was actually repeating the second line of treatment. And basically, that's it. do you think that, actually, not do you think, I know you think like that, but how can we ensure that clinical trials are yet another Standard of Care option? How can we make sure that clinical trials are part of the patient journey?

Dan Sfera (14:14)
Well, I think with oncology, it's a whole new world. know, that's oncology trials treatment. I think should be treated separately. If we do make clinical research as a Care option, it should be an oncology and rare disease. The difference between oncology and everything else is in oncology, you're not looking for treatment for

chronic condition, you're looking to get better to find a cure and hopefully not need it again or at least need it in limited doses for the future. But when you're talking about something like diabetes or obesity, you know, I think we need to be careful with clinical research as a care option just because of the slippery slope that can create for the sponsors, the payers.

Maya TrialHub (15:10)
Mmm.

Dan Sfera (15:13)
I think oncology should be treated separately in this regard. And I am for clinical research as a care option for oncology. For everything else, I do believe that the current, I guess, regulatory framework of looking at research as experimental and not treatment is the correct way to go. And I think it's because the stakes are not the same. You know, having

diabetes management or having weight loss or having eczema reduced versus having your breast cancer eradicated is two different

Maya TrialHub (15:50)
Yeah, no, I agree with you, Dan. Just one caveat, I also kind of disagree with you because I understand what you're saying and indeed in oncology you have maybe higher stakes, but with chronic diseases sometimes you may also have some huge unmet needs. And I remember when I gave birth for the second time,

For some reason, I mean, I'm not gonna go into details, but I experienced very severe side effects. One of the side effects was because I was with C -section and I had migraine, but such migraine that I can't even describe you. That was like next level pain. I mean, I had suicidal thoughts, like literally it was that bad. And migraine is actually a chronic disease, but that can severely damage your life. So.

It's not oncology, it's a chronic disease. But then again, in some cases, if your unmet need is that it's damaging your life, think clinical research should be an option. And then I don't think we should promote clinical research and let's say advertise it, like say go, like do research, not the Standard of Care. I'm just saying that if you are aware what the options are and be able to measure

the pluses and minuses together with your clinician or the PI, for example. That's one way to decide actually what is better for you because for different people, you have different preferences and different expectations. And that's where understanding the local Standard of Care is so crucial because for a patient with chronic disease in Bulgaria, you know, I'm originally from Bulgaria and someone from Germany, I can tell you the difference is very, very high.

So the motivation of someone from Bulgaria joining, even with chronic disease in Bulgaria, might be completely different than the one in Germany. But anyway, Dan, you also mentioned something different that's also very important that sometimes the protocols, not sometimes, like we've discussed that protocols are getting more and more complex. And the eligibility criteria in these protocols

sometimes exclude 90 % of the patient population. And very often, this is to do with how people are being treated. So can you tell me from your experience, how often do you face clinical trials that fail to actually understand what is the patient's journey before the patient is to join the clinical trial? And how often actually this causes difficulties with recruiting or retaining the patients?

Dan Sfera (18:31)
yeah.

Well, just about every study, but I do agree with you then in that sense on your standard of research as a care option. I was thinking from the payer standpoint and advertising and treating it treating it as an approved drug. and then the sense that you just described with we should have as many physicians as possible doing research. Absolutely. That's actually my goal.

Maya TrialHub (18:43)
Wow.

Dan Sfera (19:06)
One of my goals in life is to raise awareness and if you're a patient now, I'm a paid we're all patients. Actually look does my doctor do research in the town? I'm in a small town. I already know all the doctors who do it That's a dumb question to ask myself. But if I like when I'm in that bigger city, you know, it actually Says a lot about the physician that they do research, especially if they're not an institution that they're just a private practice

that also does research. shows me a lot of things about the doctor. It shows me about the quality of care that they look to provide. It shows me that they care enough to have different streams of revenue for their business. I think patients should be encouraged to look for physicians who also do research. So I agree with you there. Patient journey misunderstood by the sponsors all the time. And I'm on the other side.

I'm on the site side, but when I do jump over into the sponsor and CRO side, also myself fall into the trap regularly because even though I know everything I know and we're going to talk about on this podcast, I'm putting myself in the framework of what the sponsors have to deal with. And I empathize with them like, well, the regulator said you have to do

You got to do it, but there's some pushback you can do. It's a negotiation process between the regulators and the sponsor. And if you don't push back, the regulator is not going to make the trial easy for you. And the regulators could care less about the patient journey. Right? Like that's for people like Maya to figure out. That's for people like me to figure out that's for sites and sponsors. The FDA is trying to make everything safe.

for the patients. They're starting to provide guidance on inclusion with the recent initiatives around the diversity and obviously that stuff is big, but at the end of the day, their job is safety first. And the patient journeys for the industry to figure out. And that's what people like you are doing, but

Maya TrialHub (21:20)
Yeah, of course.

Dan Sfera (21:28)
I think it starts with the design. if the regulators are pushing back on, these patients need to be excluded, somebody needs to come back with evidence. Well, for these conditions, you know, this is the percentage of patients actually taking this. Like, do you want us to exclude these patients? Because that actually excludes a lot of African -Americans, a lot of Latinos. Like it's a negotiation. You have to be able to, you have to be informed. You have to know.

And a lot of these smaller sponsors don't have the budgets to do that or don't have the know -how. And this is why consulting work is booming. Even though there's job freezes, consultants have never been busier right

Maya TrialHub (22:05)
Mmm.

Interesting. Is that actually an advice that you can give to? Because I personally don't have any experience with consultants. But like, is that something that can really help by the companies overcome this barrier with regulatory authorities like FDA?

Dan Sfera (22:19)
Mm -hmm.

I think as far as the, sponsors are concerned with the FDA, yeah, they need, they need to be looking out for the, the, the wellbeing of the patients. And when it comes to the consultants, like they're, they're the ones who usually have the understanding of what the patients, what that actual patient looks like versus what the, what the, what the regulators are looking for.

Maya TrialHub (22:36)
Mm -hmm.

Dan Sfera (22:59)
And they're, they're usually talking about the same thing. It's just the regulators have everything in silos and in blocks. And then the sponsors, especially when they're less experienced, they get afraid and say, well, we have to do this. Whereas a good consultant will, come in and say, well, actually we do have this. This is, this is what they want. It's just a matter of framing it in a way that, makes sense. So it's a negotiation process, but yeah, consultants that know

All stakeholders, obviously the more stakeholders you have experience with the better, but if you at least understand the site side and the sponsor side or the site side and the regulatory side, you'll do well. And if you have more than two stakeholders experience with you'll do very well. And you're a one stakeholder too, you're a tech vendor, which is a whole nother

Maya TrialHub (23:46)
Hmm, interesting. What

Yeah, there are many stakeholders, like in that case, that you have to understand. But at the end of the day, clinical trials are complicated. What about real -world data, Because consultants, they're so precious because they have experience with negotiation, definitely. But then, can also the data help you show proofs to the regulatory that at the end of the day, you're not just making suggestions and you haven't decided on this eligibility criteria only

because that's how you feel, but that's what the real world shows you. And at the end of the day, you're right. wants to ensure FDA, EMA, they want to ensure safety, but also they want to ensure that you're bringing a treatment that's relevant for the real world, right? So can this data help you out in one way or another?

Dan Sfera (24:40)
Yeah, but oftentimes the applications are so different. the biotechs do this well, you know, they usually come with completely different mechanism of action, unless they come with the, with the generics that are repurposed. But when it's a completely new mechanism of action or a new therapeutic indication.

Maya TrialHub (24:46)
Hmm.

Dan Sfera (25:05)
the real -world evidence not that helpful outside of the safety profile of the drug. Like that's understood. If it's like a repurposed generic, okay, the safety profile is understood. If it's the same formulation, if you change the formulation, you still understand that real -world evidence becomes important. But now you're talking about efficacy, which you don't really have real -world evidence there. And if you have real -world evidence for safety and efficacy,

the FDA is probably not going to be lenient with your study. it depends on what you're going for, but yeah, real world evidence is extremely important in a lot of cases. But if you have both safety and efficacy data, regulators are gonna say, why do we need another drug in

Maya TrialHub (25:55)
Yeah, exactly. I have one last question because I know you're running out of time, but just one last question because I want to emphasize on actually what are the implications then from your perspective? What are the implications of not considering the patient journey and the local Standard of Care when planning your next trial design when drafting your protocol and so on and so forth?

Dan Sfera (26:18)
Bottom line is going to be delayed enrollments. Whatever you as the sponsor thought is going to cost you, both money wise and time wise is triple it. Your estimates are always going to be wrong. I don't know the exact data, but 90 % of trials are behind on enrollment. So, you know, what makes you different? Like the, this is the, the main reason is not understanding

who the patient is that you're looking for. A lot of times they don't exist or they're the anomaly. They're not the norm. Like they're, you know, you can't have somebody completely healthy in every other medical system but severely ill and the target system. Like that's not usually how the body works in a lot of cases. And if you're looking for a needle in a haystack, you're going to take a lot of time. Like your estimates.

The estimates are no good for this kind of

Maya TrialHub (27:24)
Yep. Thank you, Dan. I always enjoy listening to your perspective and keep doing your work because you're inspiring the rest of us, definitely, and teaching us also on all these different things that are happening from a different stakeholder's perspective. And I would just summarize. If you don't really take into consideration the patient journey,

you will end up having challenges down the road, challenges that are much harder to be fixed rather to be prevented. So do the homework, spend the time, spend the resources, but make sure that you understand the patient journey and the local Standard of Care. Thank you once again, Dan.

Dan Sfera (28:08)
Yeah, thank you, Maya. Keep doing your thing, too. We really appreciate it. We need more people like you.