Reseach Confidential_Adrienne Gaggi: this mp3 audio file was automatically transcribed by Sonix with the best speech-to-text algorithms. This transcript may contain errors.
Joseph Kim:
Welcome to Clinical Research Confidential! On this show, we highlight and demystify the inner workings of this greatly misunderstood activity called clinical research. Now, why is clinical research important? Well, it’s the basis for nearly every modern remedy for sickness and a growing method to build trust and solutions meant to optimize health. But it’s not for the faint of heart. And so on this show, you’ll hear what it really takes to succeed in the clinical research game. I’m your host, Joseph Kim, and I’ve spent over 23 years in the clinical research industry, now serving as the chief strategy officer for ProofPilot. Get ready for some adventures as we look into the underbelly of clinical research.
Joseph Kim:
Hi everyone! I’m delighted to have as our guest today Adrienne Gaggi, who has a very interesting career in clinical research and has decided to come on Research Confidential as her first podcast appearance. Adrienne, welcome to the show!
Adrienne Gaggi:
Thank you, Joe. It’s great to be here.
Joseph Kim:
So you’ve made a pretty good name for yourself on LinkedIn because you are speaking candidly about some really sensitive, hard, thorny topics around research, and we’ll get to those, but let’s start first by talking a little bit about your personal history. You have a very interesting history with regard to clinical research, like you’ve been a pharma tech and you’ve been on the site side and now you’re on the sponsor side of things. So just give us a rundown of your education and how you got to where you are today.
Adrienne Gaggi:
Yeah, I will say I’ve been passionate about drug development ever since I was little, like eight years old, I’m saying I want to be a pharmaceutical scientist, pharmacist. So that’s really what got me into it. Just passion for drugs and helping people and trying to change lives through these little chemical entities. I have a background in pharmaceutical science from Ohio State, and I have a master’s also from Ohio State in clinical pharmacology with a focus on clinical trial design. And I had a tough time trying to decide if I wanted to be a pharmacist or if I wanted to go straight into research. And so basically I promised myself with a bachelor’s, I’m like, I’m going to graduate, hit the ground running, and see where I get, and if I eventually need a PharmD or PhD, I’ll go from there. But I landed as a clinical research assistant at a small study site and quickly worked my way up. I was a study coordinator, a senior study coordinator managed that site and I bounced around to a CRO, worked at, as a CRO internationally in China for a little bit, and that was very interesting, and I would say for the last 4 years, 3 to 4 years, I’ve been on the sponsor side from larger pharmaceutical companies. Right now I’m at a small Boston-based biotech, so I’m the Associate Director of Clinical Development. So I basically plan to design and start-up all the clinical trials and their pipeline for multiple programs right now, so I stay very busy. Yeah, thank you so much for having me, Joe.
Joseph Kim:
Of course, so it’s funny, you have seen not just, well, now you’re seeing like the beginning of how drugs are made and developed, but you start your career on the retail end of things like actually working with the final patient, the final product, and then everything in between, which is a pretty interesting journey. What did you find most surprising about the retail experience, the site experience, and the sponsor experience?
Adrienne Gaggi:
I don’t know if this is the most interesting, but I think the thing that stands out is just how important patient education is about their medications. I was a pharm tech in college working on my degree and the amount of patients that would come and pick up their drugs and not even know the name of the drug, it’s, or they’re like, Go, I need my little white pill. And it’s like, okay, that could be anything, you have 15 drugs on your profile. And I think that is the most interesting thing is just educating the public on these different medications and interactions. And then going to the study site, it’s the same thing, you know, a lot of people don’t really know what is involved in clinical trials. The lack of patient education is the most interesting, surprising thing to me.
Joseph Kim:
And for someone like you and me who have degrees in science and have a passion for it, it’s a second language to us, and so we have to remember that not everyone is living and breathing this. Even very educated people, quote-unquote, if they haven’t been studying science, they just don’t know, right?
Adrienne Gaggi:
And the hard part is that they just don’t care either, that’s the biggest thing. Even my educated friends that I, you know, I try to talk about my work or about healthcare in general, and it’s like no one cares. And then now with COVID, that’s like a whole, it’s almost like controversial, like vaccines. Don’t get me …
Joseph Kim:
It’s funny you say that because for a long time, I used to say that nobody cares about clinical research either. And on two levels, like some people just like, oh, I don’t care about it, but also no one actually just cares about it. They don’t think about it at all, so it’s just not part of their existence or they’re not thinking about what it takes to have a medicine on the shelf. So yeah, good point.
Adrienne Gaggi:
Yeah, and I would say I honestly didn’t really know because when I started in college I thought like drug development, I had to be in a lab and that wasn’t really my personality. So I was always getting nervous, and I thought my choice was like being a lab or be a pharmacist on the retail side. So when I discovered clinical research, I’m like, Oh my God, I can do research and be involved with people directly, I really liked that.
Joseph Kim:
Now let’s talk about some of the hot topics that you brought up on LinkedIn, which I have often struggled with myself and I don’t have a good answer for. And when it comes to, so for our audience, which is life science and healthcare professionals, many of them don’t even know what it takes to actually run a study. And one key component of running studies is finding clinics to run them and then trying to gauge whether or not they can actually enroll this study. So tell us a little bit about that process and then we’ll get into some of the more provocative ideas around study enrollment estimates.
Adrienne Gaggi:
Yeah, I definitely can because I have done it solely by myself finding clinics and then also having a CRO help. But yeah, it’s, I, you know, a lot of my clinics from just working in that area, but basically the CRO, you know, you start up the study they propose say 20, 30 sites, and you kind of just go through the list of like recruitment rate, you know, years of experience that the PI has the number of studies, the different kinds of studies, and then if there’s any like major 483s deviations on previous trials, so I think that is the initial what you’re looking for. And then also the recruitment numbers, which I think anyone in the field, it’s kind of interesting being on the site side. It’s like, okay, yeah, you have to over-inflate your numbers, but it’s to the point that these numbers are, you know, they used to always be double. It’s like, okay, you cut the site’s number in half, now it’s like 3 to 4 times. And now all the sites are doing at least 2 to 3 times. So it’s like, okay, what’s the true number? Which I don’t honestly even care if you can only select one patient, fine, but tell me that I’m not going to not include your site, you know, as long as you have good qualifications in every other area. But it’s like, yeah, when everyone’s just overinflating their numbers and then I don’t pick enough sites. If everyone says they can do at least five patients, then I’m going to say, if I have a 50-person trial, I need ten sites. But then it gets time to enroll and they all only enroll one patient, I’m in trouble. So I think, I get it, being from the site, I get it. You want to get the study, but also from the sponsor side, it’s like there’s nothing we can do to make the site commit to that number.
Joseph Kim:
Yeah, so let’s try and unpack this because I never understand the root cause of this. Now, clearly, you’ve been on the site side, so you, you know that there’s a desire to enroll, and as some of the comments on your LinkedIn post said, sites only get paid when they enroll so everyone wants to enroll, but there seems to be this weird guessing game or this arms race of like, I can do ten patients, we’ll cut it in half. Well, we know we cut them in half, so let’s go to 20. We’ll cut that in half and that’s ten. And like, where do you think this actually started?
Adrienne Gaggi:
I think it started from when I was on the site side. And I have a good friend that’s in business development for trying to contract new studies and it’s kind of getting attention from the sponsor. It’s like, oh, you want to select the high enrolling site because you want your study to be done faster, so it’s like those sites get the most attention. I try to eliminate the guessing work by being really upfront with my site and being like, look, I’m looking for 2 to 3 patients per site from every site, and if you can’t do that, let me know, so they don’t have to feel like they have to give me like a false patient number. I also think a lot of these sponsors, like they don’t give the sites all the information upfront. The protocol that they end up getting is a lot more complex than what originally planned. So it’s not all the site’s fault at all.
Joseph Kim:
Well, what’s the balance there? Because as a sponsor, you know, you only know X amount percent of your study and you’d like to think you have the inclusion-exclusion criteria nailed down 90%. And if sites make their basis on that I&E criteria, they’ll say one thing. But you’re right, if that changes, you almost can’t fault the site, like so, let’s look at the sponsor then, like, what are we doing? Not we, I’m not the sponsor anymore, but what are sponsors doing? How are they misbehaving when it comes to selecting sites and helping them figure out how much they can enroll?
Adrienne Gaggi:
I think a lot of it is that they only give the protocol synopsis with the bare minimum. Sometimes, you know, they want to get their site selected before because sometimes it takes four or five months to get sites up and running if they’re bigger institutions. So I think kind of just jumping the gun. But I think on every, and my biggest thing with like clinical research is like honesty’s number one. So it’s like just everyone being honest or if like a site doesn’t know, like, I don’t really know how many patients I have with this disease in my database, and, you know.
Joseph Kim:
Some sites have done this before. And when I was at Merck, we used to do this, I don’t know if they still do it, but we would give them kind of like a little bit of a quick Excel spreadsheet with the top, I don’t know, 5 to 10 eligibility criteria. And we’d help them, we’d actually pay them and say grab 15 charts of people that meet the general indication and let’s run them through this criteria and let’s see how many you drop out, and let’s say it’s you pull 15 and five of them will pass those, so I’m just making easy math. So a third of your patients basically might be eligible. Now, that doesn’t mean they’ll say yes, right, they may not sign consent. Like, so have you looked at using like a more systematic way to help the site vet their own population? Or have you heard about this like catching more popularity?
Adrienne Gaggi:
I have heard about it. That’s a great idea. My approach has been that I basically just estimate when I plan my trials, I am starting just to estimate like a rare disease recruitment rate of 0.2 patients per site per month. You know, recruitment is always behind no matter what. So I’m like, okay, we’re going to act like it’s a rare disease, so that’s really what I’ve been doing, giving the numbers upfront, like how much I expect from each site I think helps. I was going to say something else. Oh, but coming from the site and seeing these studies with these impossible inclusion-exclusion criteria. When I, I mean, talking about being patient-centric, I really try to open up my criteria as much as I can while still maintaining data integrity and patients, yeah.
Joseph Kim:
Yeah, it’s a tricky balance.
Adrienne Gaggi:
Yeah, because I saw something with the FDA recently that, I mean, for an example, like HIV criteria, it’s just a norm to ban a patient with HIV in clinical trials, but there’s sometimes not actual justification for that. And having sponsors actually reevaluate all the common criteria, like, oh, no cancer in the last five years, it’s like, okay, but is that that’s what we’ve always used, but is that really necessary?
Joseph Kim:
Yeah, I mean, well, let’s take a little detour, which is like when we think about patients who’ve always been excluded, it’s women of childbearing age or potential, right? And what I always think about is, if you have a disease that’s sort of chronic like asthma or psoriasis, and if there’s never been any research done on you, as you know, on pregnant women and you’re a woman and all of a sudden now you are pregnant, it’s very hard for someone like that to know whether this drug is safe and effective, or mostly safe, if you’re pregnant. Like, what are your thoughts around that?
Adrienne Gaggi:
I personally have never seen a trial not allowed childbearing potential women. It’s usually if you’re a woman of childbearing potential, you have to have very effective birth control to be in the trial. I can say there’s extensive animal studies for fertility and reproductive systems and the drug, which I think is a lot of that data, and I think maybe if a patient gets pregnant while on the trial, they, we follow up with those patients. But luckily, I have never encountered a patient getting pregnant in one of my trials.
Joseph Kim:
Yeah, it’s to your point, like there needs to be double-barrier contraception. I’ve seen it occasionally, but it’s in the single digits. But we usually end up discontinuing them, which is, I understand. So both things are true, I understand that we want to avoid any issues around the pregnancy or the unborn child, but it also means we don’t get data for that population. At any rate, it’s one of those questions that I don’t know that we can answer, but it still comes up.
Adrienne Gaggi:
Yeah.
Joseph Kim:
Let’s talk a little bit about decentralized trials, because your other posts that really caught my eye was very provocative around decentralized trials, and it basically was trying to question this notion of decentralization as an actual real problem or capability that we should really think about. Give us your sense around why did you ask that? Well, let me quote your post, actually, it was, are decentralized clinical trials really the future, or are technology companies just making it seem like they are so they can sell us their products and services? Great question, unpack that for us.
Adrienne Gaggi:
Yeah, so I feel like everyone’s throwing around decentralized trials, which I won’t even, how I feel about the name, doesn’t make sense to me. But it’s like when I’m doing my everyday job, it’s like no one actually mentions it in the actual day-to-day life, so it kind of just feels like this thing people like wave around to get attention, but they don’t really know what it means. To me, decentralized trials don’t make sense, really. What everyone’s trying to do is centralize the trial, like the complete opposite, right? Now, trials are decentralized, they’re spread across, say, 50 study sites across the USA. Well, tech companies want to do is bring it all into one platform, you know, have the platform, do EDC, e-consent, collect the wearable data. So what these companies really want to do is centralize the data, a centralized trial, which is kind of why I feel like it’s coming from tech companies because they already don’t understand the basics of clinical trial right now or where they’ve been.
Joseph Kim:
You know, it’s ironic you say that because in the year 2000, so I started my clinical research career in 1999, and I remember right around 2000, 2001, we had something called to your point, centralized rating, which to me made total sense, right, because that means you took it out of the sites and you had it done it through a central location. And so the patients would call up a phone number and do their Hamilton Depression rating scale over the phone, then that to us was centralized rating. And the rationale was that actually, the science is better because instead of having 50 people do the rating scales, you’ll have three, so you have better integrate reliability, validity, less or drift, blah, blah, blah. Then it sort of stopped and we didn’t do a lot of things centrally, and then, yeah, in the last five or ten years people have been talking, mostly five years, I guess, the sort of decentralized trials. Tell me more about this name, because your first response was like, I’m not even sure how I feel about this name at all. I mean, is there anything more behind that other than just truly being centralized versus decentralized?
Adrienne Gaggi:
Yeah, I think the name that everyone wants to say or should say is centralizing the trial, centralized trials, having it all in one place. And I think the idea behind it is great, like streamlining trials, having what really it would be having less technology involved, because I know when I was a study coordinator, it’s like you have to log in a portal for, to do that ECG, you have to log in for the PFT. You have one system to enter data, you have another system to randomize a person, you have another system to look at the lab results. So I think, yeah, technology to put that all in one place and have one login would be amazing, and not having to like, I used to have an excel tracker just for my username and passwords. I mean, I still do, but, so I think that idea behind it is great. I also, I don’t think it’s possible for a lot of trials, specifically like phase two trials where they’re looking at safety and you have patients coming in for blood draws or PFTs, I know I do a lot of respiratory trials, immune-mediated diseases and it’s like, or a six-minute walking test, like, how are you going to make that basically virtual instead of like decentralized trials? You want like virtual trials where you’re collecting the data at the patient’s home. So I think there’s a lot of hype and I get a lot of messages from tech companies being like, look at my platform, look at this, look at that. Also, the thing that I don’t get is if this trial is really decentralized or centralized, then you’re going to need less sites. The reason we select a bunch of sites now is so you can kind of get a span of the whole United States to say, but if you can recruit patients virtually, you don’t need that many sites. So you’re asking these sites to push out your technology, and basically, it’s a lose-lose for them because if it works, they’re going to essentially lose their job in the future, in seven, eighteen, 50 sites, you might need only five, like five PIs, so that’s kind of what I don’t get.
Joseph Kim:
And that’s a real economic disruptor, right or wrong, right? That’s a huge shift in the future of sites coordinators, phlebotomists, and PIs, primary investigators, which also brings the point of if you decentralize things to Walgreens and home nurses and blah blah, blah, as far as I remember, the PI must be there to provide oversight. How they provide oversight to Walgreens to make sure things were done correctly. Do you see a way that could happen?
Adrienne Gaggi:
Well, that’s like my biggest concern too, with these tech companies. Like, okay, are the project managers GCP certified? Yeah. Who’s actually overseeing the data? I know sometimes I have issues with my PI, even logging into a portal to do their training at the start of the study, so to have some of these doctors take the time and look at all the data and if they’re going to be comfortable writing, signing off on something for a patient they’ve never met, which is I think it’s great for a lot of like mental health studies where it is just a bunch of questionnaires and you can collect all that data remotely from surveys. But yeah, for like serious diseases like cancer, COPD, asthma, yeah, I just don’t think anyone’s actually being honest with it. If they actually think like every trial will just be this virtual remote trial, I don’t know. I mean to say hybrid because I think they’re like realizing it’s not possible, so they’re like, oh, like hybrid, but also a huge thing with patient recruitment. When I was at the site, patients, their favorite part about joining the trial is to interact with the study staff. I would have patients that would keep coming back for all my COPD trials and they loved hanging out with the staff for like 5, 6 hours doing the appointment. They get a lot of attention from the PI where at your general doctor’s appointment, you see the doctor for 15 minutes. Here, they can talk to the PI as much as they want, ask any questions. So it’s like if you take that away, I’m not sure if patient recruitment would really increase. You’re taking away most of their stipend. So … the hand over their data, which I think everyone’s already a little.
Joseph Kim:
Skeptical about.
Adrienne Gaggi:
Yeah.
Joseph Kim:
Yeah, I was at a conference in Toronto last week and someone said something that the OGs, right, the originators of patient centricity were the sites, because you’re the ones who have always been talking to the patient and generating that engagement that’s human and not technology-based, because engagement is more than just do this task, do that task. It’s an emotional connection between the coordinator and the patient. So I hear that a lot, I’ve heard that from folks at Javara and Brad Hightower, we visited him last month and he says pretty much the same thing. In terms of a successful DCT or maybe more realistically, hybrid, what would it need to look like for you to actually be a believer? Like, oh, not only does this work for everyone, but it’s done with high quality and oversight.
Adrienne Gaggi:
I think, I’d be interested in the next couple of years, right now, there’s so many companies, you don’t know which ones are good. I think seeing what happens in the next couple of years of the companies that get a good reputation and provide the high-quality data, I think just time, it’s not that I’m skeptical completely, I kind of just don’t think it’s necessary. I think you should, like sponsors should be putting the money back in the sites and coordinator’s pocket, like the people that are really running it, offering like travel reimbursement for subjects, increasing their stipend to the $50 a visit isn’t really, we’ve been using that metric for like ten years now. I’m like, that’s not going to get someone in the door. So I think giving the sites more funding that they can adequately have a patient-centric trial and provide for their patients and pay the subjects, because a trial doesn’t need to be remote, if you’re covering flights and you’re covering hotels and mileage and food.
Joseph Kim:
Yeah, all great points. I think we just have to remember these are human beings and we’re asking them to basically really upend their lives for a short time, and we have to meet them where they are, which oftentimes requires fare reimbursement for the time and effort happening. And maybe with regard to study designs, these study designs continue to get more complicated. Have you seen them get more complicated or simpler?
Adrienne Gaggi:
Oh, insanely more complicated. I think when I started my career, it was like very straightforward. You had one screening visit and then the next visit was randomization, then you had treatment period, follow-up. Now it’s like the screening periods are like four visits long, then you get randomized, you have a bunch of visits. So when I design my trials, I need to be like, would I even be able to participate? Like, I think if you have a full-time job, it’s really difficult to join clinical trials. Some of these appointments take 2 to 4 hours long.
Joseph Kim:
Right, and there’s not like actually good insight into how long that will be. So I recently joined my first trial for COVID and it was always guesswork around like, wait, how long is this going to be? Or when I was left with the saliva kit to fill up, I actually made two errors on that one, and I’m in clinical research, so the confusion and complexity is definitely increasing for sure. So what are some low-hanging fruits that can be solved in the near term with regard to complexity? So take DCTs out of the mix or feasibility, but like what are some obvious small problems you think we could solve together as an industry like in the next six months?
Adrienne Gaggi:
That’s a big question.
Joseph Kim:
It is a big question, there’s so many problems.
Adrienne Gaggi:
From a technology standpoint.
Joseph Kim:
Technology, workflow, like, yeah.
Adrienne Gaggi:
I think the sponsors actually being more involved. I think they leave a lot up to the CROs. I think that’s what I would like to see, having sponsors directly connect with each site and giving them a representative to reach out to. Yeah, I don’t know what I would like to see in the next six months.
Joseph Kim:
Well, think about it and I hope you can maybe post it on LinkedIn when you think of a good answer. But I mean, I think the question is hard because there’s so many problems. One thing I continue to hear from sites is, help me make sense of the 12 different portals I have to log into, right? Seems like you’ve ….
Adrienne Gaggi:
Yeah, I would think that at this point there could be like a platform where you have all your portals, even if it’s like different links. I don’t know if that already exists, but yeah, just having one portal.
Joseph Kim:
Yeah, it’s funny you say that because that’s a feature of one of our products, ProofPilot, so we should talk later for sure. We do a lot of things to try and eliminate guesswork and orchestrate the study so it’s much easier for sites.
Adrienne Gaggi:
Yeah, it’s, you have like a mobile app that allows like the study to be directly on the phone.
Joseph Kim:
It could be mobile or desktop to make it easy because sites work in a variety of technology devices. So, yeah, you know, without being too salesy on this podcast, we can certainly continue talking for sure. But I do want to thank you for spending some time with us today. It’s really great to see someone who’s seen drug development and delivery on a number of different touch points. I’ll keep following you on LinkedIn, you have great posts, and I wish you well, thanks for joining.
Adrienne Gaggi:
Thank you so much, Joe.
Joseph Kim:
Thank you for tuning into Research Confidential. We hope you enjoyed today’s episode. For more information about us, show notes, transcripts, and resources, please visit ProofPilot.com. If you’d like to debunk a clinical research myth, share some war stories, or maybe just show our audience what kind of heroics it takes to pull off gold-standard research, send us your thoughts, episode ideas, and more to help@ProofPilot.com. This show is presented by ProofPilot and is powered by Outcomes Rocket.
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| hosted by Joseph Kim
