TRANSCRIPT
Deborah Borfitz:
Hello and welcome to the Scope of Things podcast, a no-nonsense look at the promise and problems of clinical research based on a sweep of the latest news and emerging trends in the field and what I think is worthy of your 30 or so minutes of time. I'm Deborah Borfitz, Senior Science Writer for Clinical Research News, which means I spend a lot of time with my ear to the ground on your behalf and a lot of hours every week speaking to top experts from around the world. Please consider making this your trusted go-to channel for staying current on things that matter, whether they give us hope or cause for pause. In another five minutes or so, I'll be speaking with Christine Senn, Senior Vice President of Site Sponsor Innovation at Advarra, about how to overcome some of the deadlock in clinical trial recruitment that is tied to obsolete marketing guidelines currently in place.
Deborah Borfitz:
But first, the latest news, including surprising discoveries about beta blockers, low-dose aspirin for lowering the risk of colorectal cancer recurrence, repurposing drugs to prevent breast cancer relapse, remote participation research to learn why athletes and military members face higher ALS risk, the first agenic AI platform purpose-built for life sciences and needed guidance disseminating research findings. In a breakthrough discovery from the so-called reboot trial, researchers have found that beta blockers, the standard treatment after a heart attack, especially for patients with uncomplicated myocardial infarction with preserved heart function, may in fact offer no clinical benefit and can even worsen outcomes for women. A subgroup analysis revealed that women treated with beta blockers had a higher risk of death, heart attack, or hospitalization for heart failure than women who didn't receive the treatment. The reboot trial, published in the New England Journal of Medicine, was conducted without pharmaceutical industry funding, and the new knowledge it generated is expected to reshape clinical guidelines globally.
Deborah Borfitz:
In another study appearing in the same prestigious journal, researchers in Sweden found that low-dose aspirin halves the risk of recurrence after surgery in patients with colorectal cancer harboring mutations in genes within the PIC 3 signaling pathway, a mutation found in approximately 40% of patients. In the randomized clinical trial involving 3,500 patients from four Nordic countries, patients with a genetic mutation in PIC3 had a 55% lower risk of recurrence when treated with aspirin compared with a placebo group. The belief is that aspirin makes the environment less favorable for cancer by reducing inflammation and inhibiting platelet function and tumor growth. Findings here could influence the treatment guidelines for colon and rectal cancer worldwide, particularly since the drug is well established, readily available, and extremely inexpensive.
Deborah Borfitz:
In the randomized phase two clever trial, University of Pennsylvania researchers have shown that it's possible to identify breast cancer survivors who are at higher risk of incurable relapse due to the presence of dormant cancer cells, and they could effectively treat those cells with repurposed drugs in 80% of study participants. The three-year survival rate without any disease recurrence was above 90% in patients who received one drug and 100% for patients who received both study drugs. Surprisingly, some drugs that didn't work against actively growing cancers are very effective against trouble-making sleeper cells. Two larger ongoing studies are enrolling patients at several cancer centers across the country to confirm and extend those results. Answer ALS, in collaboration with ALS Therapy Development Institute and Augie's Quest, has launched an ambitious research initiative designed to uncover genetic and metabolic mechanisms that may explain the significantly higher incidence of ametrophic lateral sclerosis among endurance athletes, military service members, and potentially other adrenaline-driven humans. Champion Insights, as it is known, will use remote participation technology to turn participants' homes into real-world research sites. The program will collect blood samples and clinical data from up to 500 participants and integrate seamlessly with Answer ALS's open access research repository. Recruitment is expected to begin in late November 2025.
Deborah Borfitz:
Medable recently launched Agent Studio, the industry's first agentic AI platform purpose-built for life sciences, which comes with an out-of-the-box CRA agent automating routine clinical trial monitoring and communication. Sponsors and CROs can use the no-code agent to create custom configured AI agents for other repetitive tasks related to protocol development and trial planning and optimization. The idea here is to remove long-standing bottlenecks in clinical development and the roughly 45% of development time new drugs spend on unproductive white space between phases. I recently spoke at length with Medable senior VP Andrew McMakinnon about Agent Studio for a story you can look for in Clinical Research News.
Deborah Borfitz:
And finally, a review of 96 published studies, including randomized controlled trials, finds that study participants don't always receive a summary of the results, although that is frequently what they want, what funding bodies increasingly require, and what most researchers consider to be a moral obligation. The practice of sharing summary findings of clinical research appears to have many benefits, notably making participants feel respected and valued and building trust. But best practice guidelines is still lacking on ways to disseminate the information, especially in lower middle-income countries. As a reminder, links to the studies, stories, and news releases referenced in this month's news segment can be found in the show notes. It is now time for my chat with Christine Senn from Advarra to learn about common log jams and getting clinical trial marketing campaigns rolling and practical tips on what to do about it. Welcome to the show, Christine. I, for one, am ready to learn.
Christine Senn:
And I'm honored to be on your excellent podcast, Deb.
Deborah Borfitz:
Oh, thank you so much for that. Um, I'm going to assume that listeners are already aware that recruitment goals for clinical trials are routinely missed since we have been talking about the problem for decades now. Advertising, of course, is one of the main driving engines to simply get the opportunity on people's radar. But several big obstacles often stand in the way. And I want to start with the most obvious outdated regulatory guidance from the days before digital advertising and now popular social media channels like Facebook and more recently TikTok. What's behind the delay in getting regulations updated after a quarter of a century? And what does that mean for studies being conducted in the modern world?
Christine Senn:
They are a bit outdated. Um I obviously can't speak as if I understand the true inner workings of the FDA, which are in flux at this point anyway. But we have all seen that updating federal regulations is complex and involves having a lot of stakeholder input, right? Extensively like public comment periods and congressional involvement, and then the intersection with other regulations like the common rule. So I do feel for the for agencies like the FDA that often struggle to move quickly, do their own internal processes, and then making sure that as technology changes, in this case, media changes, that they're looking for how to protect public the public, how to be legally robust, how to have cross-agency harmonization, including not just within the US, but also with regulatory foreign bodies. And so I suspect the short answer is that there have been other regulatory priorities that have taken precedence. But what it means presently is that many of the new digital marketing formats, be it blogs, influencers, video content, webinars, social media posts, are just either not mentioned or only indirectly addressed in the 1998 guidance. And yes, you and I are saying 1998 was the guidance for this. And what it does is it forces institutions, IRBs, and sponsors to interpret old rules for new media. And it creates an inconsistency and sometimes unnecessarily conservative applications. You know, every institution is going to have its own risk tolerance.
Christine Senn:
And when we're looking at a guidance that doesn't always work for what we currently have, we have to then review and debate the permissibility of innovative recruitment strategies that have come along since that's been written. So because of this, we're potentially restricting, could be restricting, right? Not all organizations would say, but could be restricting creative or effective outreach methods, which hamper trial enrollment. And I would also add one other unintended consequence, which is that the lack of modernized guidance may discourage sites and sponsors from really leveraging the emerging channels and technologies that do have the potential to make recruitment more inclusive and efficient. And that can be particularly disadvantageous for diverse or hard-to-reach populations.
Deborah Borfitz:
And it's sponsors that are often providing study sites with advertising materials, but I have heard you say those ads can be, you know, too specific or difficult for patients to understand. And the options sometimes don't include social media and search engines, as you just alluded to. Obviously, this could conflict with what sites believe they need. Can you speak a bit about how this centralized approach can sometimes hinder the very things sponsors want to see better trial enrollment figures and who might not be reached because of this more specifically?
Christine Senn:
Yes, certainly. And now, to be fair, of course, sponsored initiated trials could be a huge asset to sites because they do offer recruitment methods to all the sites uniformly. And in doing so, the sponsor and the central IRB it chooses are able to ensure consistency in the participant messaging and have just much more efficient approval timelines. That said, there are issues with the materials not being effective at time, um, at times. So, first, what's provided may not offer options for all advertising types, such as social media posts, search engines, patient letters, and even still some sites or some trials want flyers. So, sites may want some things that they're that they are not being provided by the centralized advertising. And I think create, I think the trouble here is that creating a great centralized marketing plan requires knowing one's blind spots. So a centralized marketing department may not or ad agency may not have all of that.
Christine Senn:
And I'll give the example that I came from a site network that had every therapeutic indication. And I will say that they recruited very differently. You know, there might be similarities in some types of chronic diseases, but then very different from oncology, very different from surgical, uh, very different from acute. So until someone has tried to recruit for a variety of therapeutic conditions and done so in a variety of location sizes, big city versus small town, for example, and within different types of patient communities, it's frankly very difficult to know those blind spots. And so for this reason, my recommendation would be to create many more types of centralized materials. And that counterintuitively might actually cut down on cost because perhaps site would sites wouldn't need as much, haven't wouldn't have as much of a need for creating their own materials if they had all options available to them. But I would like to actually talk about the too specific part too, because I think this one is it can be lost as well. So this usually occurs, uh a site is usually, I'm sorry, an ad is usually too specific.
Christine Senn:
What and it happens when a sponsor is looking to ensure the ad is recruiting only for their trials and not for others. You know, so they don't feel like they're paying to recruit into a competitor's trials because we would know that every endocrinology office is likely conducting more than one type 2 diabetes trial at a given time. So what they do as a protective measure can be to include too much information in that ad so that it's really for their trial, so specifically, but it's more information than patients can digest. The thing about advertising principles is that advertisements are supposed to grab your intention and pique your interest, right? So you want to go get more information, but these overly specific ads actually overcomplicate the message and quite frequently turn off participants' curiosity.
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Deborah Borfitz:
Yeah, getting back to why sites uh can and often do spend their own money to create ads. Um, but that can create a new log jam because sponsors need to consent to the materials that will ultimately be submitted to the IRB for its approval. And who's to say if sites are any better than sponsors at creating, you know, riveting and yet regulatory compliant copy? Um, any advice for sites taking this path or sponsors and CROs working with them? Oh, yeah, I have advice for everyone.
Christine Senn:
No fear. So sites honestly have to absolutely understand the FDA guidance and the role of the IRB. Um, you know, many sites do have their own, their own IRBs, and that is great. And it sometimes is sort of a black box, whether they use it's a central IRB or a local IRB. Does the clinical staff or the person making the ads really understand what the IRB's purpose is? So the IRBs review materials for a few very specific aspects. They are looking to ensure they are not coercive, that they do not specifically state or imply guaranteed benefits, um, that they refrain from over-emphasizing the compensation participants might receive, and that they clearly indicate the investigational nature of the treatment. So I'm going to add examples of those, and they are going to be from actual errors made by sites and just to get a sense of how much the site needs to understand before they submit. A dermatology trial cannot show before and after pictures of problematic skin and then fully cured skin because it implies guaranteed effectiveness. But that is something that can commonly be seen by the IRB. Um, an ad cannot include a cartoon figure holding a bag of money that shows participants getting paid a large sum of money for their participation. Definitely not okay.
Christine Senn:
And then, of course, you can't hide the fact that it's a research study. So those examples are actually a little hard to share because some of it's a little, it's a little like, oh wow, a cartoon bag of money. But this is how this is where sites can go, can go astray, I think, in trying to make their own ads. Um, so knowing the regulations and really looking at best principles, not only in advertising, but in the FDA guidance is hugely important. As for sponsors, they really need a process for site-initiated advertisement. So you mentioned this, not all sites want to create their own materials, but larger institutions, site networks often do, especially if they've created their own marketing department because they see it as so integral to their recruitment success.
Christine Senn:
Uh, earlier the show, I was part of a panel, actually. We had representatives from sponsor, a sponsor, a site network, and an IRB. So I would like to channel my sponsor colleague who was on that panel because I asked her what she said. And she expressed that not only do sponsors have need to have their own process for site-initiated ads, but they also need to make that process clear to the CROs they work with. That ends up being a big issue for sites, where a site will is told that they need to have everything go through a CRO and will send the site initiated advertisement to the CROs who then are not always sure what the process is to handle it, send it to the sponsor. If the sponsor doesn't have a process, then the CRO can't really do anything. And we I promise you it's been more than one case where sites have had trials close to enrollment, those fast enrolling trials, before it's ever before these ads have ever been approved, which is unfortunate because there's just a lot of wasted time. So with recruitment, with patient recruitment being such a massive concern as sponsors lose millions of dollars due to enrollment delays, it just doesn't make sense not to have a process that gets rid of duplicative or otherwise inefficient steps. So the point my sponsor colleague Fred made is that a key component is training. She said, just ask these questions. Is there an identified person for each step of the process? And does each person know what they're reviewing for specifically and what the expected timeline of their review is?
Deborah Borfitz:
Very good. Wow, there's a lot of pros and cons all the way around here. Uh what, what uh what reasons do sponsors generally give for keeping the creation of marketing materials in-house rather than setting up a process, complicated though it be, uh, where they review and approve ones conceived by sites who who who theoretically know their community best and are more apt to get the language and messaging right?
Christine Senn:
Yeah. Well, typically sponsors do understand the regulatory guidance and IRB specific guidelines around recruitment materials particularly well. Um, I would say too, I would think that sponsors could reasonably be expected to be best at creating compelling advertisements because they can hire quite seasoned ad agencies or create internal departments and then also be able to look back at the prior trials and learn from their prior enrollment outcomes, you know, successes and failures and A-B testing and all the things they do in advertising. But, you know, unfortunately, and in addition to what we've already discussed, it seems like many ads are just created without a strong sense of health literacy principles. So with wording being confusing to patients, you know, it could be that words are of too high of an educational level. And we see this more from sponsor ads than the site ads. So it's like using the word stipend instead of the word paid. Um, stipend is we all think it's a very common word. It's really not a common word in in in just general day-to-day language. Um, it could be that the phrases are too obscure, like using the phrase investigational product rather than study drug.
Christine Senn:
Product doesn't even sound like something you want to be part of necessarily. And this one's gonna sound really weird because you're you're gonna say, how could accurate medical technology ever hamper enrollment? Okay, so this is gonna be a weird one. But if you're glad you're here for the ride. Um it, if you're if the accurate medical technology does not jive with, I don't know what other word to use, uh, with the local lingo, it doesn't work that well. So I'm gonna tell you what happened for us when we were on um when I was in clinical research sites in Georgia and Alabama, and we were recruiting, this was years ago, back for um COPD trials. We could not get this, is this is a pulmonary disease, okay? So we couldn't get any patients to book appointments with us when we use the sponsor provided script or the newspaper ads that use the acronym COPD. Our clinical staff, after a couple months of this, because they talked to patients every day, they ended up with a far better sense of how to tailor language for patients in general, but also for specific communities. And this one in particular, they said the word that our communities use for this was emphysema. So if you're a pulmonologist, you're going to say, well, medically there's a difference between emphysema and COPD, but that's irrelevant in this case because the people who had COPD called it emphysema. And so as long as the pulmonary function tests proved COPD per the trials inclusion criteria, we were able to help patients and ethically enroll participants for our sponsor clients. But it took us getting a site-initiated script approved with the word emphysema to become top enrollers in COPD trials.
Deborah Borfitz:
That is really interesting. And I never would have thought that those two two words have been in would have been confused myself, but yeah, flexibility is sometimes required, right? We're all different. Okay, now, not knowing when FDA guidance on clinical trial advertising will get updated. Do you have any parting words regarding what, if anything, IRBs can do to help modernize the process?
Christine Senn:
Probably an open mind in looking at your own internal processes is always a benefit. So each individual IRB should really take an objective look at their own review guidelines. It is certainly possible that some IRBs, probably not centralized IRBs, right? But that IRBs have had their processes for quite some time. And because this guidance hasn't changed, why would they need to change their guidances? But technology has changed so much, and the way that we communicate with patients has changed so much that it's worth looking at them at their own processes. So questions you might ask would be, you know, do the requirements of our IRB translate to the current state of technology within the industry? You know, are the changes we request necessary to fit the mission? And what's the mission? Protecting patients. Or are we overly focusing on editorial changes? That can happen because as long as you're protecting patients, the editorial changes are should only be for that, right? Not for the other things that go into an ad. And as objectively as possible, you know, can we look at our review guidelines and see where we have perhaps made it harder for participants to understand what the advertisement is trying to convey? You know, we can get so caught up in, this isn't just IRBs, but it could be anyone getting so caught up in how we're doing something that we miss the point, which is to enroll qualified patients into trials.
Christine Senn:
So I think the regulations allow for IRBs to institute restrictions that um go above and beyond the letter of what's written. But when it comes to trial advertisements and recruitment, does being more restrictive actually add any protections or just is does it just make it harder to enroll? So focusing instead on what the regulatory guidance says and limiting the changes only to those items that violate the guidance or directly impact patient safety, I think that allows IRBs to operate more efficiently and more importantly, allows for greater consistency, um, uh not only among individual reviewers, but just uh across IRBs in the industry as well.
Deborah Borfitz:
Yeah, good points and good advice for sure. Thank you so much, Christine, um, all the way around for today's um feedback on all of my questions. So appreciate it. Um, and I'm hopeful um all of your advice does not fall on uh the wrong ears, but the right ears and and and and set some new new ways of operating in action. Um, thank you so much for taking the time to be on today's show and giving all those that collectively contribute to the research process, sponsors, CROs, IRBs, sites, um, a little something to think about.
Christine Senn:
Absolutely. You know, I think we're all here just trying so hard to make it work, and we really are an ecosystem. So it's really nice to be able to talk about a topic that hits every single domain. I really enjoyed this.
Deborah Borfitz:
Yeah, me as well, Christine. Uh and as always, a big thank you to everyone out there for listening in. If you're not subscribed to this podcast yet, please consider going to Apple Podcasts and doing so right now so you don't miss your monthly dose of news and perspectives. You'll be hard pressed to find anywhere else. And if you're up for it, I'd also be so very grateful if you'd leave a rating and a view while you're there. For more straight talk on studies involving humans, visit clinical research newsonline.com. And if you're a clinical research professional, we hope also to see you at our next Scope Conference, where we make things happen. Bye for now.