Medical Affairs Unscripted | MSLs in Clinical Trial Enrollment

Episode 22 of the Medical Affairs Unscripted podcast series with Dan Hennessy, PhD.

Having a clinical trial that is properly supported and engaged is no easy feat, but accomplishing this can greatly improve the success of your asset.

In this episode, Peg Crowley-Nowick, PhD, MBA, President of Medical Affairs Consulting at Lumanity, and Dan Hennessy PhD, Vice President of Medical Affairs at Merus N.V., meet for a second time to discuss medical science liaison (MSL) and stakeholder engagement. They delve more specifically into the key role that Medical Affairs plays in accelerating and improving clinical trial enrollment and highlight how to use MSLs and a Field Medical team in different ways to ensure that you get the most value from the team, both from a US and a Global perspective. As they conclude, they explore what kinds of skills are required of a well-prepared Field Medical team and how to ensure they are properly prepared.

“From many of your podcasts you have the question about “Ah ha” moments. An “ah ha” moment with respect to Medical Affairs involvement in supporting clinical trials is that a very small team can make a very big impact in the feasibility stage. And when I say the feasibility stage, that’s that initial outreach, introducing yourself and getting an understanding of the basics of how they’re set up. Do they have a tumor board, do they have a multidisciplinary team that’s involved in diagnosis and trial and treatment decisions? So, in that stage of a clinical trial, an MSL would have a wider bandwidth to reach out and engage dozens and dozens of sites over the time period of maybe the three to four months where you might be in active feasibility.”

Dan Hennessy PhD

Podcast Series: Medical Affairs Unscripted

Hosted by Dr Peggy Crowley-Nowick, in Medical Affairs Unscripted we explore a range of topics related to the strategic role of medical affairs from the perspective of industry experts. Through these conversations with our guests we will share first hand experience to provide the listener with insights and knowledge about the evolving role of medical affairs.

Episode transcript

Peg Crowley-Nowick 0:57

Welcome to the fourth season of Medical Affairs unscripted. Thank you for joining us, and for subscribing. I’m your host Peg Crowley-Nowick, Head of Medical Affairs at Lumanity. During this podcast, we will explore a range of topics related to the strategic role of medical affairs from the perspective of industry experts. Through these conversations with our guests, we will share firsthand experience to provide the listener with insights and knowledge about the evolving role of medical affairs. Please stay tuned at the end of the podcast to learn more about Lumanity.

Peg Crowley-Nowick 1:44

I’m super excited today to have Dan Hennessy, Vice President of Medical Affairs at Merus, joining us for another conversation on Medical Affairs unscripted. Dan was one of our first guests back in the first season of this podcast. And a lot has changed since we were in the midst of COVID. And now life has gone back to whatever the new normal is, we thought it was a great opportunity to get together again and talk a little bit more about MSL engagement, stakeholder engagement, and this time I’m hopeful that we’ll be able to talk a little bit more about the role of medical affairs, medical science liaisons in the support and guidance for enrollment and clinical trials. So, Dan, welcome. We’re so happy to have you.

Dan Hennessy 2:31

Thank you, Peg. It’s fantastic to be back with you again, on the Medical Affairs unscripted podcast.

Peg Crowley-Nowick 2:38

It’s going to be a great conversation because I know that you are one of our more popular guests and people are very interested in understanding how to improve their stakeholder engagement, how to use field medical teams – medical science liaisons – in different ways, and how to make sure that they’re really getting the value from the teams that they have and thinking about that from a US and global perspective. One of the things that interests me is that you are leading basically a global organization that is still in development with investigational agents. And your team is very active in thinking about how to engage — how to support the development teams as they’re attempting to enroll patients on trials. So, taking your experience now, I’d love to understand a little bit more about your thoughts on the role of Medical Affairs in clinical trial enrollment.

Dan Hennessy 3:36

Absolutely. I think the analogy of the bridge — if you’re thinking about commercialization, utilizing Medical Affairs as a bridge in terms of the understanding of how to adopt a new therapy into clinical practice, can be applied in the early and late-stage clinical development in utilizing Medical Affairs in that engagement to accelerate the understanding of an investigational therapy. As we know, a clinical investigator is also a clinician that has a lot of therapeutic options, so the knowledge and understanding that leads to a decision to participate in a trial, and then when participating in the trial, how to be really an effective and active site and investigator for that trial can be greatly enhanced through the same type of scientific engagement and dialogue that you might have in other settings of clinical practice for approved therapies.

Peg Crowley-Nowick 4:42

And how does the dialogue happen in the clinical trial setting? Is it different? What type of conversations are you having?

Dan Hennessy 4:50

Yeah, I think where you have the tailwinds is that we know that cancer medicine is a team sport, we’re living in this golden age of tremendous innovation in both therapeutics and diagnostic medicine. I think people understand the impact that we are making from incremental gains. So, the openness and willingness to have a conversation about a novel therapeutic is fairly universal. So, I think that that initial conversation to explain a novel therapeutic, explain the science behind it — that’s something that might be different for a therapy or a therapeutic class that has been in the field for several years. So, there is that need for that initial introductory conversation to clearly explain the science, the mechanism, the unmet need, and the general direction of that clinical development program.

Peg Crowley-Nowick 5:58

And by having those types of conversations, do you find that the clinical investigators are then more interested, more willing to consider their patients in these trials? Or is it just something that starts the education process?

Dan Hennessy 6:15

I think it absolutely has an impact. We see certain examples of clinical trials and how they operate. They’re really large enterprises, they’re very complicated, you may have hundreds and hundreds of sites. There is a tendency to treat these as transactional projects and programs whereas sending out personal invitations to participate in a clinical trial, maybe attaching a publication or two — it’s not the same conversation starter as meeting someone face-to-face, first trying to get an understanding of their clinical and research interests, and then utilizing that forum to introduce a novel mechanism of action or a new clinical trial. So, I think starting on that basis can certainly have an impact on the interest level to participate in the trial. But even while a clinician is participating in the trial, we’ve seen dividends in terms of their engagement and accrual enrollment activity.

Peg Crowley-Nowick 7:33

And there are so many options today for clinical trials that an investigator could participate in. Anything that gets you a little bit of attention and interest, so that they’re scientifically interested in the concept of what you’re trying to do is so, so critical. But what you’re telling me then is that from a Medical Affairs perspective, you’re participating from the earliest stages from the time of early identification of sites, all the way through trial enrollment, is that correct?

Dan Hennessy 8:06

Yeah, where the opportunity arises that I think could be a benchmark is really utilizing the knowledge gained from even your phase one to dose-escalation into your signal generating trial, and utilizing the knowledge gleaned from that trial to your phase 3 study and involving medical affairs early.

Peg Crowley-Nowick 8:32

And the Medical Affairs team has so much exposure from a data perspective, from a thought process perspective of what’s happening in the design of the trial. That certainly puts the medical affairs team in a great place to have those conversations and to bring a different type of spark to the conversation and excitement than you might have if that’s all done through a fax or just through some email contact.

Dan Hennessy 8:58

Absolutely. The richness and the texture of the conversation, and also as you mentioned, just breaking through the noise. I recall at a recent conference, speaking with a well-respected clinical investigator, mentioning that on one day, he received 17 emails about one individual clinical trial. So, these are 17 emails about one clinical trial. You multiply that across different clinical trials and different clinical trial opportunities. Breaking through the noise and being able to have that conversation is a night and day difference.

Peg Crowley-Nowick 9:39

Absolutely. Talking now about how you operationalize this thinking first about the planning, and is this something that’s just a one-off? (Is this) something that’s planned? How are you preparing your team to start thinking about going in and doing this kind of engagement for an extended period of time?

Dan Hennessy 9:59

Yeah, it really has to start with a very thoughtful approach to your internal cross-functional planning. Obviously, the clinical operations team and your clinical development team may or may not have experience working with medical affairs organizations early in development. So, a lot of the early planning involves building the relationship internally and making sure that everyone understands the operating model and the basic functions, roles, responsibilities of a medical affairs team vis-a-vis a clinical operations team, which also requires a tremendous amount of engagement with investigative sites. So, I think having that dialogue, and also having that working relationship is absolutely critical. Working through that and having a comfort level with a communication plan, and the right communication channel also involving the CRO is very important in terms of operationalizing Medical Affairs supporting clinical trials.

Peg Crowley-Nowick 11:07

I can see the importance of making sure everybody on the entire organization and team understands roles and responsibilities. So, you can all play towards the same goal and not step on each other’s toes, and potentially alter the operations. It’s such a critical piece. Thinking about a team, what size team of liaisons could actually do something like this for a company? And let’s try to simplify it for maybe one trial. Because if you start, I don’t know whether it goes up exponentially as you add more trials, but if we’re just trying to keep it simple, what do you think is a typical size for a team that could accomplish a lot for clinical development?

Dan Hennessy 11:51

You mentioned aha moments, and I know from many of your podcasts, you have the question about aha moments. For me an aha moment with respect to medical affairs. involvement in supporting clinical trials is that a very small team can make a very big impact. So, a rule of thumb is that a single MSL, if they have a substantial amount of their time to allocate can support roughly 15 to 20 sites, in an ongoing study, being able to support ongoing communication, ongoing updates to new data that’s coming in, in the clinical landscape, having conversations to perhaps understand competing trials and other therapeutic modalities that may have an impact on your clinical trial and that eventual approval and adoption into clinical practice. So,15 to 20 centers per MSL allows you to really go in quite a bit of depth. If you back up a little bit earlier into an earlier phase of the trial where you’re at a feasibility stage, you may have slightly more bandwidth to cast a wider net in the feasibility stage. And when I say the feasibility stage, that’s that initial outreach, introducing yourself, and getting an understanding of an investigator’s research interests, their clinical practice, how they’re set up, just the basics, not really the operational aspects of their investigational pharmacy and their research nurses. But the basics of how they’re set up— Do they have a tumor board? Do they have a multidisciplinary team that’s involved in diagnosis and trial and treatment decisions? So, in that stage of a clinical trial, an MSL would have a wider bandwidth to reach out and engage dozens and dozens of sites over the time period of maybe three to four months where you might be in active feasibility.

Peg Crowley-Nowick 14:07

Excellent. And how does that work for a global study? Do you need people in other countries? Is this really handled virtually so that you can do it from one country? Or how do you think about it from that perspective?

Dan Hennessy 14:22

In my experience with global trials, when you’re at that stage, and you’re up and running, and you’re in active feasibility through a global trial — you have a clinical research organization, you have a CRO onboard. I’ll go back to the importance of having clear RACI roles and responsibilities where you’re not confusing investigators and sites and clinicians and even internal stakeholders about who’s doing what. Quite simply, the clinical operations team and the CRO have responsibilities for operational aspects of the trial. Where medical affairs can take responsibility and ownership is the overall relationship and the scientific communication. So, the initial introductions and getting to know the site and the center. Communicating your initial data from your earlier stage program should have already occurred prior to going into this feasibility. When it comes to having this active feasibility, now there’s quite a bit of work for a large multicenter global trial — you may be reaching out to 3, 4, 5… 800 sites to run a phase three study with 150/250 sites. So, you do need to rely on the CRO’s local resources in the country or the region of interest. With that said, I have found it enormously helpful to have your own medical affairs resources that are on the ground locally. Something as simple as having one of those early conversations about your data, answering a question about the protocol, something as simple as scheduling that meeting when you’re one or two time zones away versus trying to schedule a meeting with the Asia-Pacific region is very important. Cultural and linguistic differences can be important as well. We had, in a previous experience, an example in which one of our Asia-Pacific countries who participated in an investigator meeting and appeared very engaged in the conversation, and the clinical trial was not very active in terms of enrollment. And we were lucky enough to have a local investigative science liaison on the ground. And through some additional digging and probing, what unfolded was that there was some clear lack of understanding about certain parts of the protocol, that no one wanted to raise their hand in a large investigator meeting and convey that they have some of these questions. It may be deemed rude to ask questions or to question the sponsor in a certain environment. So, having that person on the ground was very eye-opening in understanding some of the questions that were leading to barriers to patient selection and accrual. So that’s just one example of (why) having those boots on the ground is important. And we know that every clinical trial has a certain stage where you’re going to run into hiccups, and having a triage pathway where maybe the medical monitor and the CRA has reached the end of the line with a certain touchpoint or requiring a certain response. And then having someone with a preexisting relationship to have a follow-up as part of a triage path of a dedicated communication plan is another way of (how) having those local boots on the ground can keep things moving forward in a clinical trial environment.

Peg Crowley-Nowick 18:04

I would also imagine with local boots on the ground, you’re engaging probably with the PI of the study, maybe also with some of the study staff but more towards the PI is that a typical or are you also working with the study staff?

Dan Hennessy 18:19

It’s most typically the PI, occasionally there’s other investigators, other clinician investigators that are sub-investigators on the trial. That’s something that I would always encourage my local staff after building that relationship with the PI — Think to the sub-I’s because the sub-I’s are the PI’s of tomorrow, those are the rising stars of tomorrow, and really broadening that engagement to the extent that your bandwidth allows that. Other important elements to really having that slightly broader engagement is understanding how patient referrals may come into that site of care. You understand that all healthcare is local, and systems are very different in terms of both reimbursement and clinical practice and the degree of specialization that impacts the referral and the flow of patients into a site of care setting that can also conduct clinical trials. So, you may be surprised to learn about, even, language barriers outside of a metropolitan area of Western European countries that you assume are very fluent in English. You know, we’ve had examples where translating your data, translating your protocol, and providing messages and materials that can be communicated with these referral centers has been very helpful. That’s not something that always comes up right off the bat in your early site startup and feasibility discussions. So that’s where having those relationships, broadening those relationships, always asking the question, “How can we help you?”, you can elicit some of these aspects where having local team members that are articulate in the science can help and support that investigative site.

Peg Crowley-Nowick 20:20

So, the insights that you collect by having these conversations can also help internally make decisions on investing in some of the translations, maybe in decisions, if they have to change something in the protocol, it may have come from some of these conversations. So, things that you might not hear, or you might not hear as quickly, couldn’t happen if you have somebody going in and engaging more frequently at those sites with the PI to understand what’s really going on.

Dan Hennessy 20:46

Absolutely. When you when you think about, even outside of our industry, just in everyday human interaction — sometimes it’s really that fifth or sixth or seventh time where you’re really having a conversation with someone that, the depth of what you’re hearing back, and maybe the ability to have your guard down because you know each other, you trust each other — And that’s where you have a different level of insights that that can flow through that longer-standing relationship versus this transactional approach that you’re reaching out once, “We want you to do X, Y, and Z. We want you to participate in our trials, so we’re going to push out our information to you. We’re not necessarily using our ears to listen to you, understand you, understand your research interests, or clinical practice.” It’s that mindset that allows you to develop a relationship over time that allows you to elicit the insights that are helpful for ongoing trial operations.

Peg Crowley-Nowick 21:51

Yeah, there’s a lot of evidence that’s been developed probably in the last ten years, maybe eight years, that demonstrates that — engagement with the sites, especially from a field medical science liaison perspective, can significantly impact the acceleration of enrollment. And yet, so often, I’m not talking to companies that are actually using their liaisons in that way, and a lot of that comes from some of the challenges, as you mentioned earlier — that piece that you have to get over is everybody has to communicate, everybody needs to know their roles and responsibilities. Are there any other challenges?

Dan Hennessy 22:33

I think so. I think you have the challenge of an investment; you’re making an investment decision. And having a field medical team supporting a clinical trial is not a miniscule investment. These resources require a budget. And we also know historically that many, many trials get completed, and we have a track record of trials being completed. I have no doubt that a well-resourced company can outsource a huge amount of your clinical trial to your CRO to include some of that engagement activity. I don’t believe you have the same quality of the engagement, but I think it’s the barrier of having to make that investment on top of everything else with a clinical trial. That can be challenging. The other challenge is that it’s messy — starting this is messy, and you are likely to have some fits and starts with respect to the communication. People get confused, and that can cause tension If they don’t understand, “Why would I have someone engaging with our sites when we have a medical director? we have our CRO?…” I even use the example of the clinician that had 17 emails from the site. They don’t want to annoy the site with over-communication, so that is a challenge to which I would say it is worth the investment — the financial investment, but also the investment in doing the work to establish an operating model with clear lines of communication, where you have an organogram that you know, all the way at multiple levels, who is the point of contact for which issue. If there’s a major conference with new data, and we think it would behoove us to have a conversation with that investigator so that they understand that, who’s doing that, and if you’re having a face-to-face meeting, making sure that you’re giving the courtesy heads-up to other staff members, either internally or with the CRO, that you’re going to be joining a physician for a meeting, or perhaps even piggybacking on a meeting to share some information to be efficient. So, starting that process can be confusing and can be a bit messy at first. But in the long run, what it does is it opens up the channels of communication and opens up channels of trust that in the long run can really assist in the execution of the trial.

Peg Crowley-Nowick 25:28

Going back to the cost of starting this up, there’s a significant cost to a trial that has delays in its enrollment, and that cost has a significant impact on peak sales for many years to come, so, into the future, it’s very hard to recover from that, so that investment really needs to be looked at closely. And as more information becomes available on the impact on enrollment, because of the fact that there’s a greater understanding of what is being done in the trial, because there’s an understanding of what the company is trying to accomplish for patients, it certainly can change that trajectory, and that’s going to be important.

Dan Hennessy 26:10

Absolutely. And that mindset of this enterprise decision and a longer-term view of the investment that you’re making and what that translates into, both the near term and the long term, is very important. If the initial investment/financial and maybe the internal tension (of) implementing a new operating model is going to reduce your enrollment period by six months, that’s huge — you can never get six months back. You know, quite often companies that are engaging with medical affairs to support a phase three clinical trial; most frequently this is happening when there’s a problem and you’re past the startup, you’re past the initiation visit, so you’ve saved on that initial investment, but you’ve left some opportunity on the table to have all of your investigators that are at your investigator meeting, maybe they’re just swooping in for 10 minutes to listen to this one section, but if they would have already had an in-depth clinical conversation to start with, those are the opportunities that you’re leaving on the table; And just even the opportunity to have a trial finishing earlier and being commercialized earlier. So, thinking about the whole picture and not waiting until you have a fire to put out is a very important trade-off to consider in this investment decision.

Peg Crowley-Nowick 27:47

Absolutely. So, you have the investment decision that can sometimes be a challenge, and then second is the internal communications and working with the clinical development and the clinical operations organizations. I like what you said — it’s about establishing those relationships, it’s showing respect, because under any circumstances, from a liaison perspective, you should be engaging with your other colleagues and making sure that everybody’s aware of what’s going on, and how everybody’s treated on that team can make a significant difference in the success of, not only the trial, but also in the relationships that are built.

Dan Hennessy 28:23

Absolutely, absolutely, and I’ll just make a brief comment that clinical trials are so highly regulated in so many aspects of what they’re doing operationally: setting the schedule of visits, consenting patients, understanding the window of time for which they can come in for study of related procedures, and so forth. This requires a solid understanding of the mechanics of a clinical trial that your medical affairs expert is not necessarily going to have that expertise beyond, you know, surface level. So it’s really a collaboration where you’re able to utilize the expertise with clear roles and responsibilities, where you can both have the appropriate engagement. You know, that’s really where you can make a positive impact on a trial.

Peg Crowley-Nowick 29:18

A great point that you just mentioned in there is understanding clinical trial practice and how that gets done. What do you have to do to train the team that’s now engaging with the clinical development, clinical ops team? Do you really need an advanced and senior MSL team or is this something that you train for? What do they need to know?

Dan Hennessy 29:43

I think if you’re defining their responsibilities towards the scientific engagement in that that KOL relationship, and the purpose is to have this an introductory interaction around the science your previous data, any preclinical or clinical data in the trial design, you don’t need to have an in depth training on 21 CFR and understand that the same level of training that that a CRA is undergoing, it depends on how you want to deploy them. So, having that initial discussion discussing data discussing competitor data is very much within the wheelhouse of, of an MSL that has a couple of years of experience. So, it does not necessarily require this large investment in additional training. Where I would say it makes sense is to ensure that that MSL, even if they’re not presenting the protocol, they’re not, you should really leave certain aspects of, of safety and adverse event reporting, things of that nature. You don’t want to step on the toes of the medical monitor or other parts of how you’re how you’re communicating that information. But they should understand the protocol inside and out, they should understand the investigators brochure. I think a well-trained MSL has already done that, even for a commercialized compound. One of the areas where operationally Medical Affairs can be very helpful when you’re scaling to a large phase three study is presenting some of the background material and the data at an investigator meeting to broaden that understanding beyond just the PI to other site staff. So that’s another area where simply your internal Medical Director, are they going to be able to participate in 150 site initiation visits over a six-month period of time? Do you want to defer this to staff at the CRO that does not have the same, perhaps, history and understanding of your internal compound program and strategy. So again, some of the similar training on a compound the competitive landscape would prepare an MSL to be able to, to execute and participate in SIV as the resident expert to describe here’s the background of the disease state. And here’s, here’s the background of the data and introduce the clinical trial.

Peg Crowley-Nowick 32:31

And it sounds like that alone would set somebody up perfectly to enter into this role, and for the company to gain a lot of value from their engagements. Dan, this has been a great conversation. I think it was very interesting to hear your opinion on US versus global and the need for some local boots on the ground. The investment in a team, whether they’re called medical science liaisons or have another name and medical affairs to engage in with clinical development and clinical operations to really support the understanding and the knowledge that’s necessary for the sites to feel comfortable participating in these trials, helps significantly with enrollment, that seems very clear, some training is necessary, but really pretty much along the lines of what you would do in a typical commercialized product for a team that’s dealing with a commercialized product.

Dan Hennessy 33:32

Absolutely, if I may even interject with a further point and some of the value you might derive from involving medical affairs early — really the ability to have a much more seamless transition of institutional knowledge towards commercialization. So, your traditional path where you’re maybe starting to build a medical affairs organization or pulling in an existing medical affairs team that’s involved with a commercial product’s portfolio into a clinical trial six months prior to launch, where the phase three study has been completed. All of that institutional knowledge from the FAQs in the questions that come up during the conduct of the trial, and really having that point of contact also involved in communicating to clinicians as they’re thinking about adopting an approved therapy into clinical practice. So really, that seamless transition of institutional knowledge is another area that’s quite important as we think about the long-term benefits of having earlier engagement in clinical trials.

Peg Crowley-Nowick 34:47

And I don’t think that can be ignored because just the time that’s saved and in getting that institutional knowledge built is a tremendous savings in the overall, if the trial is successful, in the overall scope of the commercialization process. That’s a very, very nice point, and I think (it’s) a great point to finish on. Thank you very much for sharing your knowledge of the use of field medical MSL organization and medical affairs organization to support clinical trial enrollment.

Dan Hennessy 35:21

Thanks for having me, Peg.

Peg Crowley-Nowick 35:27

At Lumanity, we focus on improving patient health by accelerating and optimizing access to medical advances. Because it’s so important for patients to have access to life-changing innovations, we provide consulting and strategic services to medical affairs organizations. Medical Affairs programs designed by Lumanity can help you recognize the most important insights from your in-house and field teams. And then capitalize on that data to develop strategic Medical Affairs plans, strengthen your engagement with thought leaders and build cutting-edge data generation programs. Success in these areas allows the medical team to provide leadership and demonstrate maximum value to your brand and organization. Our clients can also benefit from broader capabilities and expertise across commercial market access, real world evidence, HEOR and communications. Lumanity is here to help you. You can reach us at ma-info@Lumanity.com.