RARE Daily

Mapping Spheres of Influence

January 4, 2024

Key opinion leader and digital opinion leaders, terms the bioharmaceutical industry uses to identify influencers, play a critical communications role. They not only can help raise awareness and drive acceptance of innovative products, but also serve as a conduit to help inform companies about what matters to patients and doctors, give insights on clinical trial design and site selection, and help recruit patients for studies. Adnexi identifies and scores KOLs and DOLs in specific areas to help biopharmaceutical companies identify the critical influencers they need to seek out. We spoke to Sandra Shpilberg, co-founder and CEO of Adnexi, about the role KOLs and DOLs play, how Adnexi identifies and measures their influence, and what companies need to consider when engaging them.

Daniel Levine: Sandra, thanks for joining us.

Sandra Shpilberg: Thank you, Danny. I am so happy to be here with you today.

Daniel Levine: We’re going to talk about key opinion leaders, digital opinion leaders, and the way the pharmaceutical industry is changing the way they seek to communicate with patients and physicians because of social media. Let’s start with some definitions. I suspect many people have heard of KOLs or key opinion leaders. What defines a KOL? Who are they and what role have they traditionally played within the pharmaceutical industry?

Sandra Shpilberg: That’s a great place to start. A key opinion leader is an expert in the disease. So traditionally, key opinion leaders are identified by the quality and the quantity of their scientific and clinical activity. So scientific and clinical activity can refer to authoring, peer reviewed papers on the disease or treatments, writing treatment guidelines for that disease, serving as clinical trial sites for clinical trials, presenting at medical congresses, and even advising biopharma companies and getting paid for that. These are all activities that assume that this KOL treats or has access to a significant pool of patients, and therefore they become really interesting to biopharma to engage with. KOLs, by the way, go by many other names in the biopharmaceutical industry. Sometimes they’re referred to as thought leaders. Some companies refer to them as key external experts, KEEs, lots of different names. But at the end of the day, KOLs are going to be deeply involved in all stages of product development. I have brought biopharmaceutical companies from clinical trials to pre-launch planning all the way to launch execution and helping those patients eventually learn that this new treatment is available. And because KOLs are deeply involved, I always like to use this formula–EMC², which is that the interactions with KOLs should be: E early, M meaningful, C consistent, and double C collaborative. So early on, as early as possible, biopharma companies have the opportunity to begin to build relationships with those that are deeply entrenched in the treatment of patients. Meaningful, ideally, in this relationship, there’s a great degree of meaning. We’re working on clinical trials, we’re working on generating new data, we’re working on publishing that data. We’re working on letting patients know where to go join a trial or where to eventually take this new treatment. Consistent, these relationships should be consistent throughout the entire life cycle of the treatment. And of course, collaborative. We’re collaborating here. We know that in the biopharma space, there are at least four stakeholders. They’re all important at all given times. There’s the biopharma company, there’s the patient, and they are the most important. There are these key opinion leaders, doctors, HCPs, that are treating the patient, and of course, there are the insurance companies that are enabling access to those treatments. So EMCC in terms of how to build these relationships with KOLs.

Daniel Levine: A newer phenomenon is digital opinion leaders or DOLs. Who are they and what is their sphere of influence? How do they differ from KOLs?

Sandra Shpilberg: So DOLs are digital opinion leaders and they’re also experts in the disease, but they’re relying on digital media to communicate their messages about the disease or their treatment of interest. So instead of publishing in the Journal of Endocrinology, they have their own YouTube channel, and they post weekly about treating a specific disease. And the truly powerful aspect of the DOL is that because they use these mass platforms like YouTube, Instagram, and TikTok, their content is generally available to massive amounts of people, both patients and HCPs, and like a peer reviewed paper that takes months to publish, sometimes years, their content is available as soon as they’re willing to post it. And the content is also more digestible, usually shorter, more patient focused. So they present a great opportunity for education of patients, for information about clinical trials, for information about treatments. They’re really a great source of information for patients and HCPs alike.

Daniel Levine: Part of the reason these people matter as much as they do to the pharmaceutical industry, hasn’t it in part to do with human behavior and the way people make decisions. How do these influencers drive behavior, particularly around adopting innovations?

Sandra Shpilberg: Yeah, so even though biopharma is in the business of science, those involved in all aspects of treatment, development, and launch, as well as those eventually taking the treatment, are human beings. And human beings are known to rely on each other to make decisions. So trust plays on important roles, stories play on important roles. Seeing people just like me being treated for my condition plays an important role. And so with key and digital opinion leaders, really the opportunity is for them to share this type of content that can influence patients and can also influence each other, right? We know that doctors train under each other, they refer patients to each other, they collaborate with others in clinical trials, and these relationships are formed, and these relationships is from where influence stems. So I think there’s different parts to this influence opportunity. Somebody may influence because of their title, they may influence because of the type of content that they’re putting out there. They might influence because I know them personally or they’re speaking about a story that is so relatable to me that I am going to take on that influence. So that is sort of like how influence works in terms of digital opinion leaders and key opinion leaders and the content that they share in order to achieve that influence.

Daniel Levine: KOLs have been ingrained in the biopharmaceuticals industry approach to marketing for a long time. To what extent have DOLs been recognized and embraces a critical way of talking to patients and physicians? And what’s driven the need for the industry to recognize the importance of these people?

Sandra Shpilberg: Yeah, great question. So DOLs are certainly a newer topic for biopharma. However, more and more biopharma companies are embracing this concept. And the reason why is because patients and caregivers are online. We know that, right? They’re on Facebook, they’re on YouTube, they’re online searching for information, searching for support, searching for new treatment opportunities. And so, if biopharma wishes to intersect these patients and caregivers with adequate education, these DOLs can play a key role. Now, I always like to say this, you could either find a DOL or you can make a DOL. So we help find DOLs, and these are the experts that are already having a YouTube channel. They’re already posting on YouTube or on Instagram about major depressive disorder or thyroid eye disease or another rare disease that you wouldn’t expect anyone to be posting about. But the other opportunity is for biopharmaceutical companies to have their own YouTube channels in which they invite certain experts to speak about the disease and maybe eventually about the product.

Daniel Levine: And why would a KOL or DOL want to engage with a biopharmaceutical company? What’s in it for them?

Sandra Shpilberg: So, there’s several potential benefits for a KOL or DOL to engage with a biopharmaceutical company. The first is they become associated with a new treatment or an innovative product, and that’s generally a good place to be, where, as a DOL or a KOL, you are being called on to participate in clinical trials or to advise on how a clinical trial protocol should be set up. So these are really great opportunities. Two is the opportunity to be exposed to treatment education from the biopharmaceutical company before others. These KOL and DOL relationships are prioritized relationships within the biopharma companies. And so, as a KOL or DOL, they’re likely to receive education information sooner than the rest of the treaters would get that information. And then finally, there’s the opportunity for that KOL or DOL to participate in activities that can significantly develop their career. So, these include participating in clinical trials, which can lead to peer reviewed publications in important journals like The Lancet or New England Journal of Medicine, which often leads to publication of new treatment guidelines. That would be more for a KOL. For a DOL, it might be that their channel becomes bigger because now for some reason, the company is also supporting the content that is being shown. They are, and it reaches patients much faster. In my career in biopharma, I’ve seen doctors who were considered emerging opinion leaders begin to be groomed by a biopharmaceutical company to participate in these different types of activities. And over a course of five or 10 years, they’ve really grown in their influence and the types of activities that they were involved in.

Daniel Levine: How have biopharmaceutical companies traditionally identified who the KOLs and DOLs are?

Sandra Shpilberg: Yeah, so for KOLs, traditionally this was identified way back. It was mostly like pen and paper. You would have a chief medical officer who would go deep into the disease to understand who was treating, who was doing research, and then we would start building a list. And that list would be 20 to 30 people manually collected, immediately outdated. And one of the things that’s very clear for biopharma is 20 to 30 KOLs isn’t going to do it right. They’re going to need a lot more in order to go through all the different stages of development. In terms of DOLs, I think companies mostly go online and then start searching and see what they can find, who is out there sharing information about the disease. And the way that it’s been done without the use of technology is largely a manual effort that ends up in an Excel spreadsheet.

Daniel Levine: You and your son are co-founders of Adnexi. What is Adnexi and what does it do?

Sandra Shpilberg: Yeah, Adnexi is a software solution for biopharma that helps to find and profile key opinion leaders and digital opinion leaders for any disease across the globe. And then we also measure their influence. We measure their peer influence. We want to help biopharma find the KOLs and DOLs that matter most in that disease. This is so drug development and launch can be accelerated, and these innovations can reach patients faster and better. In my previous life, I’ve always worked primarily in rare diseases and complex conditions. So at the end of the day, the patient that is benefiting from a faster treatment is really benefiting because they have a complicated or serious condition. And so, with Adnexi, this is a software solution. We’re using algorithms to process massive data about key opinion leaders, about digital opinion leaders. We also create our own unique data based on influence surveys that we do with peers. And we bring all of that together to help biopharma not only prioritize who they need to be in contact with, but have enough of these connections to be able to support all of the clinical, commercial, and medical affair activities that need to take place.

Daniel Levine: So, when you were working for biopharma, one of the jobs you had was a product manager. How does this change the process for someone like your old self in connecting with KOLs or DOLs?

Sandra Shpilberg: Yes, it changes it completely. So back then, I manually connected the information in an Excel spreadsheet. As I mentioned, the information was primarily based on who the company already knew and who they knew, who those KOLs knew. And maybe at that point it contained 30 to 40 KOL names. But the commercial efforts that were required to sustain an effective launch required so many more KOL relationships that weren’t those 30 to 40. One other thing to note here is that because generally in that KOL identification that biopharma does, they’re choosing people that are very experienced. One of the risks is that about 20 to 30 percent of them will retire within the next five years, and that is a very, very meaningful and important fact to work around. And so back then, that’s what we did. I collected 30 to 40 names, about 10 to 15 retired before the product was even launched. And we needed more, right? My spreadsheet was immediately outdated, and I had no way to stay up to date on the scientific activity of all the KOLs that we were managing. So, with Adnexi, what we’re doing is we’re bringing the technology to the entire process of finding and profiling, keeping those profiles updated daily and automatically. And all of this is done with direct and algorithmic connections to all the major sources of information like PubMed, clinical trials.gov, the NIH. And new data comes in every single day. That helps to re-rank and identify new potential KOLs. In addition, now we’re using AI, artificial intelligence, to read the treatment related publications and assign a sentiment to both the publication and the KOLs involved so that as biopharma sees some of these key opinion leaders in our database, they can already tell if this person is positive, neutral, mixed, or negative on the specific product that they’re working on.

Daniel Levine: What’s the business model for Adnexi? Do companies engage you for a project? Is it a software as a service model? Is it something else?

Sandra Shpilberg: Yeah, we generally work on project fees that contain a software subscription. So all of the companies that we work with are on the platform. They have access to the data 24/7 for as many of their users as they like. And obviously the database is very deep and it’s going to contain thousands of KOLs even for the most rare diseases that we’ve been working on. And then with the project fees, what we do is we generally have a project that we’re working on, like some specific strategic questions that we’re trying to answer at the time that the project begins. And so, it’s a mix of both having the software available to the company and to us at Adnexi, but also applying a strategic consultative view to be able to answer the specific question that the biopharma company has at that time. These questions can be questions like we’re getting ready for a phase 3 trial, which should be the top 30 to 40 sites that we should think about for a phase 3 clinical trial. It could be questions like we are getting ready to put together a publication group to begin thinking through new treatment guidelines for this disease. Who should be in that publication group? Who has been most influential in a certain country in terms of the treatment of this disease? So these are the specific questions that we attempt to answer in addition to the data that is provided in the platform.

Daniel Levine: Walk us through some examples, take it out of the abstract and give it some concrete setting of how this was used by an actual biopharmaceutical company.

Sandra Shpilberg: Yes, I’d love to talk to you about a biopharma company that was working on the global launch of a new treatment for a rare disease. This launch was in 20 countries, and like many rare diseases, this disease was known by about five to 10 different names. And this is not uncommon, and one of the advantages of our platform is that we customize the universe that the biopharmaceutical company is going to see for that disease. And so we can search for an unlimited number of inclusion and exclusion search terms to define what that disease universe is. So with this company, we helped them in a number of ways. First, we were able to deploy the Adnexi platform to help them identify the top scientific leaders in the disease for each one of the top 20 countries. So, these are the traditional KOLs who’ve published the most, who’ve done the most clinical trials, who’ve written treatment guidelines, who speak spoken at congresses. We help them with that. Then after that, we help them to understand which one of those KOLs were already familiar with the treatment and what their sentiment was. Was it positive, negative, neutral? This is where we use AI to read through the publications and determine the sentiment. We also helped them identify the digital opinion leaders posting content on this rare disease. And this was really interesting because I expected that we were going to find around 15 to 30 digital opinion leaders, experts, healthcare provider experts posting about the disease. But instead, we were able to find 60 digital opinion leaders posting content. These are healthcare providers who are experts in the disease having their own YouTube channel or Instagram account or TikTok account. I’m posting about this very rare disease in order to educate patients and in order also get new patients to join their practice. And then finally, we conducted Adnexi influence mapping in 10 countries. And what that helped them do is it helped the biopharmaceutical company, one, confirm that some of the KOLs that we had discovered through the scientific method were also influential, and two, find brand new healthcare providers who may not have published that much, but they were considered to be very influential in the treatment of this disease. All in all, this really helped them accelerate the launch and become more targeted in their approach in terms of identifying who were the most important key opinion leaders and digital opinion leaders that they should cultivate relationships with.

Daniel Levine: You talked a little about this in the context of the KOLs, but there’s an opportunity here to really have information flowing in two directions, not just using KOLs and DOLs as conduits for communicating to patients and physicians, but to really learn from these opinion leaders to inform things like clinical trial design. How are you finding companies using this as a source of market intelligence?

Sandra Shpilberg: Yes, absolutely. I want to emphasize that the information to and from KOLs flow in all directions. So basically, KOLs have the opportunity to influence each other. They have the opportunity to influence payers sometimes, and they have the opportunity to influence patients. And in the same way they have the opportunity to share information about any of those back with the biopharmaceutical company. So KOLs and DOLs are often invited to participate in advisory boards or market research or other surveys, or even more informally taken out to dinner to ask what are the expected advantages that you see in this new treatment? What are the expected challenges that you see with patients adopting this new treatment? So, there’s definitely an opportunity for the information to flow both ways, both from KOLs and DOLs to patients and to each other, as well as from KOLs and DOLs back into the biopharma company to provide intelligence about what to expect when this treatment goes to market. And I’ve experienced this obviously myself back in my roles in biopharmaceutical companies where the key opinion leaders and sometimes in very informal ways at a dinner would be the ones that get to very strategic issues that are going to appear in the launch. And it’s only through those conversations that we get to tease out, okay, this is an expected challenge for this launch that we can begin to prepare for.

Daniel Levine: How about in terms of patient enrollment. What have you seen on that front?

Sandra Shpilberg: Yeah, so KOLs are instrumental in product development. They are generally going to be involved in the clinical trial. By identifying the right KOLs, a biopharma company is most likely to access those large pools of patients that could be included at first in a clinical trial and then later on prescribed an approved treatment. When we think about the traditional key opinion leader with lots of scientific activity, those are the very likely clinical trial sites for a phase 3 clinical trial and therefore, they’re really instrumental. Identifying them early, identifying them for their influence is really important to ensure that we’re getting to the right pools of patients for a clinical trial, and that long-term, the biopharmaceutical company is in the best possible place that they can be for the prescription of the approved treatment.

Daniel Levine: This is a highly regulated industry. Are there any particular consideration companies need when engaging KOLs or DOLs from a regulatory perspective?

Sandra Shpilberg: So yes, when it comes to engaging with KOLs and DOLs, all regulations that affect interactions with a possible prescriber are still in effect. So let’s say a biopharma company will engage 10 key opinion leaders in an advisory board to get feedback on their clinical trial protocol. Well, the materials for that meeting are still going to be subject to review by compliance, and those payments that are made to those advisors still need to be reported following the Sunshine Act. Or let’s say a biopharma company will provide some materials to a DOL in order to educate them on the disease or a new treatment. Well, those materials will still have to go through a promotional review board or promotional review committee, PRC. There’s many acronyms that are used for this depending on the biopharma company. But basically, bottom line, Danny, all regulations still apply when engaging with KOLs and DOLs. There are potential prescribers and therefore all regulations that apply to those interactions apply to them as well.

Daniel Levine: I think of KOLs being more bound by regulations. But in terms of DOLs, is there any advice you would have to patients online who are viewing comments from these folks and there’s no disclosure requirement if they have any economic relationship with a biopharmaceutical company. Is there any advice you’d give to just people in the digital media world for how to evaluate things they see online?

Sandra Shpilberg: Yes, absolutely. The advice basically sums up to be a careful consumer of online information, right? So for example, let’s say I suffer from disease X and I go online and I search and I find a YouTube channel, and it happens to be that it seems to be a doctor. The most important thing that I can do is actually research if that’s an actual doctor, is this an actual doctor that has treated this disease? Do they have some kind of affiliation that I recognize? Like with any content that we consume online, it’s very important to know the source of the information and to then take it a little bit with a grain of salt. Do we think that what this person is seeing is educational? And a few of the things that you can look for is the person, actually a healthcare provider. That’s a great place to start. There are also many patient advocates posting, there’s also patients posting, but that’s a good place to start. Is this person a healthcare provider that treats this disease? Is this person affiliated with a reputable and recognizable entity? And then three, is the content that they sharing—does it seem to be of quality? And maybe as a patient, sometimes it could be hard to ascertain if it is correct or not. But at the end of the day, it is content that you’re consuming online. So always consult your doctor before making any changes or decisions that you would make to your treatment based on something that you saw online. Now, what I think where the DOLs come in is that many times they share patient stories, they will have a real patient on their channel come in and talk about the disease. I think that that’s where some of the content becomes really valuable and seeing other patients that are traveling through the same journey for this disease and seeing how they’re handling and how they’re getting through the different challenges and opportunities that may arise.

Daniel Levine: Sandra Spielberg, co-founder and CEO of Adnexi. Sandra, thanks as always.

Sandra Shpilberg: Thank you, Danny. It was great to be with you today.

This transcript has been edited for clarity and readability.


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