Garth Sundem   00:00

Welcome to this episode of the Medical Affairs Professional Society podcast series: “Elevate”. I’m your host, Garth Sundem, Communications Director at MAPS. And today we’re exploring the evolving uses of real world evidence and Medical Affairs with David Thompson, CEO of OPEN Health Evidence and Access, Tracy Mayne Vice President Global Medical Affairs at Intercept Pharmaceuticals. And Miriam Tarallo, Director of RWE and Partnerships at Pfizer, Italy. This episode is sponsored by OPEN Health. So David Tracy, Miriam, we have a lot to cover today. And I know that RWE in general, is a very hot topic with the MAPS audience, even more specifically, moving RWE, from an afterthought to the planning process is a hot topic within the MAPS membership. So I’m excited today. Thank you for joining us. And Dave, I was wondering if maybe you could start us out with some of the background. I know you’re a health economist, and I’ve done a lot of work in RWE. So what is RWE in relationship to ato AR and what is the relevance for Medical Affairs?

David Thompson   01:27

Yeah, well, thanks, Garth, and happy to get the ball rolling. As you say, I’m a health economist, I’ve been doing RWE or real world data analysis since well, before the terms real world data and real world evidence were coined and became part of our everyday lexicon. So the first one that I did actually dates back to early in my career, the the 1980s, in which we used real world data from healthcare claims to do analyses. And this was, you know, a key part of the, you know, health economics and outcomes research, you know, toolkit, and it has been over the years. And it’s, it’s interesting, because more recently, in the past, say, five to eight years, when we started talking about real world data and real world evidence, the uses of these data have grown beyond the HLR and market access around and if solidly entered the realm of Medical Affairs, and I think we’ll talk about, you know, some of the reasons for that. But one of the key ones is clearly been regulatory interest in using RWE for their decision making. And this has taken things to a whole nother level, because once you know, groups like FDA, and Ema get involved with things, then it’s, you know, something that has more regulatory activity, more definition gets brought to it, government funding comes into play. And it’s really it’s been a game changer for for the whole thing. And Medical Affairs has always had a kind of an overlap with with Hu R. And R, WV. Because of the interest in funding phase four research and phase four research is quite often geared towards and generating real world outcomes of care, as opposed to clinical. So there’s always been that little piece, but that piece of overlap, but once we started pulling regulatory into it, and broadening the, you know, array of stakeholders in the healthcare system that have an interest in RWE, that’s when Medical Affairs really, you know, came to the fore, and has taken over the RW II generation function in many pharma companies.

Garth Sundem   04:03

Well, I imagine that in the 1980s, looking at claims data would not necessarily have been part of a submissions package. But But Tracy, do you see? Do you see more acceptance now? And is this universal acceptance is our is RWE coming into? I don’t know legitimacy? Is that the right word?

Tracy Mayne   04:25

Well, it’s interesting, if you look at the FDA, they have been using real world data to look at evidence of safety or the lack thereof for decades. So so the FDA has been very comfortable with the use of real world data within that realm. But it was really what the signing of the 21st Century Cures Act in December of 2016, that Congress mandated FDA to find a way to integrate that into the assessment of efficacy. And in 2021 the last quarter, the FDA released four guidances on the use of real world evidence for fulfilling PMR and for labeling. So it’s really the transition of going from safety to efficacy that we’re now seeing happen now. And it’s interesting because in at the end of March, the FDA is going to, has put out an RFP to do demonstration projects to advance the use of real world data to demonstrate efficacy of of products. What we have seen, though, is there are several companies that are in the position of mine, where, because of our timeline of approval, we are having to integrate that real world data into our our snda submission packages. Now. So it’s a little bit ahead of where I think the FDA anticipated being right now. And so I think some companies are really pushing to say FDA, we know you were you were on a pathway to be doing this, but it was a slower pathway than the the needs of individual product to dictate at this time.

Garth Sundem  06:01

Miriam, are you seeing the same thing in Europe? How does it compare to what Tracy is describing with the FDA?

Miriam Tarallo   06:08

Yeah, the EU is a little bit a step back compared to FDA. But in European real world data are becoming increasingly important if you think that the between 2018 and 2019. Over 40% of email authorization requests included the real world data, it is clear why the European Commission in the pharma strategy for Europa has proposed to use real world data and new evidence generation and evaluation methods to support the development approval and utilization of medicine. Actually one of the priorities of the EU Commission for the year so 2019 2025 is the creation of a European health data space to foster and facilitate the access to health data such as electronic medical records, genomics and registry data. And actually, they have developed a data governance actor to foster data sharing, and the next step is to complete the data to specify who can access the data and how and during pandemics, this process has been accelerated actually. And we can see that the main recommendation of the regulatory science strategy to 2025 published by EMI March 2020 is to promote use of high quality real world data in the decision process. And actually, the big data work plan 20 to 25, that is based on the regulatory science strategy to 2025 have very ambitious goals. So over 100 studies of the Darwin EU, which is the data and services network in Europe, for a better use of real world evidence in drug evaluation 100 studies within 2025 Also, they published that good practice guidance for the use of real world data. And it is followed by a public catalogue of all the European real world data. Obviously, Europe is is not a single country is made of many different countries. So the challenge is to apply this same rule. So for all the members that end up basically, there are some countries like the Nordic countries that are more advanced for cultural, if you will, the digital digitalization process that is much more developed than in other countries like Italy, where we really need a health data governance contact and a data actor because there are several barriers to access to data. So our work has Medical Affairs here is really to raise awareness, build a solid real world evidence, culture, and also shape policy to an A to embrace the European health data governance and DATA Act.

Tracy Mayne   09:18

Actually, to jump in, I’d like to jump in on that theme. When you look at the FDA guidances. They are expecting these real world studies to be conducted very much in the same way that they conduct clinical trials. So you know, pre specified protocols submitted to the FDA with the FDA being able to weigh in on those, you know, before you begin the studies, the collection of data, the custody of data, the transfer of data, the analysis of data, all of which are expected to be governed under SOPs that CROs like OPEN Health have impact legs. So so they are really elevating the, the data collection and the execution of the studies to be as close as possible to, you know, really the norms that they’ve established for clinical trials. In fact, I wonder, David, if you want to having having worked together on this, if you might want to comment on that?

David Thompson   10:21

Yeah, exactly. I think it’s, um, I recall being in meetings with FDA, where they said, Yes, 21st Century Cures mandates that we utilize RWE for decision making, it does not mandate that we lower our our data standards for, for quality data for decision making. And, you know, Tracy made the point earlier that FDA has a high comfort level, over a long period of time for using real world data for, you know, ongoing safety surveillance for products out on the marketplace, the real issue is to what extent and when FDA will be comfortable utilizing real world data instead of clinical trials. And that’s where everyone wants to push, because obviously, the economics of it are tremendous clinical trials, cost 10s of millions of dollars to perform. And real world studies, you know, tend to cost about a fraction of that. So the economics, certainly incentivize sponsors to pursue RWE whenever possible, not just the cost, but the time as well. So when we have available data that we can, we can mined, and we can construct rigorous comparative research, then it makes sense to do so.

Tracy Mayne   11:49

And David, on that same line. So real world data has actually been used for drug approval and in labeling, but it’s been used exclusively in ultra rare diseases, where you’re just never going to be able to do a clinical trial, and also in pediatric and in oncology indications. So what we’re seeing now is the boundary is being pushed into rare disease, and into indications outside of pediatric and, and oncology. So so there is precedent of using those real world data, but it’s in been in very, very specific areas and indications.

Garth Sundem  12:31

Okay, so this would have to be after the first approval, correct? Because that’s only at that point that you’d be generating real world data?

Tracy Mayne   12:41

No, actually, it’s it can be a part of the initial approval. So in ultra rare diseases, they will they will, there are instances where they’ve done single trials, where the comparator has been a real world external control group.

David Thompson   12:57

Yeah. And, and, again, it’s an instance in which FDA is very amenable to single arm trials in those instances in which having a control arm in the trial is either unethical, because it denies patients one last chance at a life saving treatment, or it’s, it’s, you know, just not feasible because there just aren’t enough patients there. And that’s why, you know, it steers towards the oncology rare disease realm.

Tracy Mayne   13:28

And actually, that’s another point, you know, Garth, when you said, you know, why, why now, the other interesting thing that happened is in, in rare disease, there was, you know, clearly recognition. David, as you said, the economics against doing studies and bird disease, were almost insurmountable doing an outcomes trial could take decades. And the cost of bringing a drug to market was in the billions of dollars and the economics are against them developing drugs for 10,000, or 50,000, or even 100,000 patients. So the FDA, and the EMA created pathways for accelerated or conditional approval, where your drug was approved based upon a surrogate endpoint of let’s say, a biomarker, but then there has was a post marketing requirement that said you had to do an outcomes trial. The problem is, once your drug is on the market, if you’re a patient and you you’ve you’ve been randomized, and you know you’re either getting drug or you’re getting placebo, and you’re watching your disease progress. Patients you know, who are who are randomized placebo can kind of figure it out, and they go on commercially available drug, your insurance company is going to pay for it. The question is why, you know, would you why would you stay in a trial if you think you’re on placebo if your insurance company is gonna pay for your drug. So the problem is the accelerated approval and rare disease created a paradox that made it in some cases simply infeasible to do a confirmatory trial. file. And that’s where real world data can then be used to fulfill those post marketing requirements for full approval and those guidances were written, you know, really specifically with that in mind.

Garth Sundem  15:14

So Miriam Tracy was saying that you can, in fact, have RWE as part of an initial submission package. That, of course, means we need to be planning for RWE activities. Do you see RWE planning going earlier into evidence generation planning, and even into into launch planning?

Miriam Tarallo   15:38

Oh definitely, I mean, if we think about the purpose of Medical Affairs, we aim to shape the end to end life cycles of our medicines, with the clinical insights that uncover anticipate and address population and patient health needs. Therefore, real world evidence is really a crucial capability for Medical Affairs and needs to be included very early in the medical strategy, we can start from the burden of disease, the unmet clinical need, we identify the population that would benefit the most, from our innovations. And the real world data can also improve the governance of access to medicines can improve the patient journey in the the entire healthcare part of our patients. Obviously, this process involves multiple stakeholders, like regulatory agencies, payers, clinical and scientific societies. And obviously, last but not least, the patient. Therefore, our work really requires partnerships with all these stakeholders. And they normally involvement from very early phase one when we think about innovation, and why is needed. So real world evidence, is really a key capability for Medical Affairs and the pharmaceutical industry.

Garth Sundem  17:10

Of course, because real world evidence is not just the effectiveness and safety of emerging technology, it’s burden of disease as well. So what other types of real world evidence go into the early planning process? Tracy, or David, what do you think what else goes into early planning?

David Thompson   17:33

Well, I’m just going to jump in here, because you make a good distinction, Garth, that’s important. There’s, there’s essentially two uses of real world data real world evidence in in, you know, sort of across the product development cycle. One is that real world evidence that needs to be generated, to sort of pave the way for the introduction and launch of a new medicine, and then support commercialization efforts. But there’s also a second use of real world data, which is to assist in strategic planning for clinical and commercial, you know, strictly internally. So, you know, so one widespread use now. And there’s actually, you know, several companies whose founding premises to do this, which is to use real world data sources, as a means to refine the, you know, clinical protocols for trials and to ensure, you know, they, they refer to this as assessing protocol feasibility. So, you take draft, study, inclusion exclusion criteria, you overlay those criteria onto a real world data source, and it gives you have the opportunity to see how stringent those selection criteria are on the opening pool of patients and, and maybe you get to the bottom of implementing all those criteria. And you’ve winnowed out 98% of potential patients in that instance, you know that your trial is going to have a tough time recruiting. And you can use these data sources to assess slight tweaks to different selection criteria such that you can improve the size of the overall patients, you can similarly use these data sources to then try to simulate outcomes of the trial in those instances in which the data exists. So there’s a whole cottage industry associated with simply using real world data sources to you know, refine and improve clinical trial design. So there’s examples like that in which it’s not something that’s, you know, for publication or for dissemination in any way, but rather has a critical part of the strategic planning process for clinical and commercial as well.

Tracy Mayne   19:58

Well, and David, you talk You know, the clinical development sort of sort of side? And you’re absolutely right, both geographic and practice targeting. I mean, you can, you can identify practices that have large numbers of qualifying patients, and recruit those for clinical trial sites. The other areas that come to mind, you know, incidence and prevalence of disease, you need to to define that to have a sense of, you know, how large is your target population, the burden of illness and establishing unmet need? Being able to understand the basics of how are you going to create a value story, I mean, you know, the costs of toenail fungus versus the cost of dialysis. If you’re able to offset all the toenail fungus costs, the value proposition is always going to be somewhat more limited than if you’re actually preventing someone from going on dialysis. So I would say in all four of those, those different, you know, areas, defining incidence prevalence, burden, value story, and then using it to target clinical trial are really critical pre launch areas in which real world evidence can really be quite crucial.

Miriam Tarallo   21:07

Yeah, I completely agree with that. You don’t need my previous career at Pfizer, I was working in ATR, before moving to Medical Affairs, and we would use real world evidence to create the value proposition of our magazines starting right from the burden of disease to understand what is the value of innovation of our innovation in this landscape? What is the cost effectiveness of this new drug compared to the standard of care or available treatments? Also, to understand the unmet need of patients treated with the standard of care, Was that enough? These are all important questions, especially when you prepare for a launch of a new drug. So these are all activities that needs to be incorporated early. And define the value story for our medicines.

David Thompson   22:21

There’s one other question that I’m always interested in, I’m not, I’m not within the pharmaceutical industry, and both of you are so I’ll, I’ll toss it your way. Which is, you know, I’m always curious to know, how pharmaceutical companies organize themselves internally and how they avoid, you know, stepping on different departments stepping on one another’s toes. And so you have, as we’ve discussed, you have Medical Affairs, you have HLR, you have, you know, pharmaco epi departments, you have market access groups, all of which, and, you know, not to mention patient centered outcomes, all of which have some, you know, stake on the RWE. Claim. And, you know, how have you have you seen, you know, your own companies sorted out or others? And what are your thoughts on, is there an optimal way of addressing this?

Miriam Tarallo   23:23

I can take this question. You know, I think that it’s a matter of cross functional collaborations, because each of these different stakeholders, does a different piece, but cannot have success without the piece of the other department. So, at Pfizer, we approach the real world evidence generation starting from something that we call the evidence blueprint, which is a document that it’s owned by the medicine team, which is a cross functional team, involving HR EPI, real world data real, yes, real world data department and so on Medical Affairs, and we see it all together and identify what are the data gaps, what are the data needs? What what is the need to generate specific data? What is the strategy for generating those data and all together, decide what is the medical strategy and PHS are the HR strategy to deliver real world evidence? And then each of us does his or his piece and we’ve been the story together. So I think it comes from very good cross functional collaboration and planning.

Tracy Mayne   24:52

From from my side and actually going through this right now. What I found is that the that spiritual sort of reporting structures really go out the window, and you have to be working within a cross functional matrix team, you know, so So you know, as we’ve been doing this regulatory submission, you’ve got to be working with your with your regulatory folks, because you know, what you’re doing, it’s got to fit, you know, within the SN da and has to, you know, fit within the, you know, highly specified environment of regulatory submissions, you have to be working, you know, with clearly your clinical development, folks, especially if you’re doing external controls, you’ve got to be working with your biostats department about how is your data organized and marshaled I mean, you know, mine has been in education on C disk and Adams datasets, you got to be working with your data management, folks, you’ve got to be working with your quality team, because, you know, the FDA audits of real world data have to be done. And they don’t look like traditional clinical trial audits, in some ways. And in other ways they do, you’ve got to be working with your medical writing department, because you’ve got to create clinical study reports. So you are you’re working in a highly matrixed environment with folks that you may not have traditionally been used to working with so so closely. So in that sense, it has been tremendously exciting, and, but also a pretty steep learning curve.

David Thompson   26:25

Okay, so let me put it to you this way, whose budget is that coming out of because you both talked about the matrix approach to things and ultimately someone has to pay and therefore, it’s coming out of their budget, and they are the most accountable for the success of the whole enterprise? Was that Medical Affairs?

Tracy Mayne   26:44

It actually, it’s, it falls into Medical Affairs and clinical development. It’s it’s not just falling into into and then part of in a part of it is you’re figuring out, okay, once the submissions done some of the stuff then becomes more purely just Medical Affairs. So it’s it’s matrix, not just in terms of reporting structure, its matrix in terms of budgeting too.

Miriam Tarallo   27:07

Okay, I agree, I agree.

Garth Sundem  27:10

Here’s the question, David, what what is your perspective, as a health economist, that people looking at RWE from within Medical Affairs may not have?

David Thompson   27:23

So yeah, I think what you might be trying to get at is to what extent does the scientific expertise need to be brought in house, I think pharma goes in waves with respect to how much they want to take, take things in house versus, you know, go to kind of these skeletal models in which they outsource HLR, RW, e generation, and a whole lot of other things as well. And, you know, there are instances and there are examples of companies that have spent huge sums of money on bringing in and licensing various real world data sources, bringing in platforms, and you know, data lakes and these kinds of things, to put those sources in and facilitate analyses. And then, and then, you know, hiring data scientists, epidemiologists, health economists, to internalize that function. And you know, that, that approach has its merits, you can sort of create your own internal all you can eat buffet, in which you’re spending, you know, 10s of millions of dollars for the investment, but you can generate hundreds and hundreds of studies internally. And some of which can could then be, you know, fashion for external dissemination as well. I’ve always thought a more strategic and tailored approach is preferable. I enjoy the opportunity to work with our scientific colleagues on the pharma and biotech side. I’ve always been impressed by, you know, what they bring to the table. And I think that feeling is mutual.

Tracy Mayne   29:14

And from the pharma perspective, because I’ve been I’ve led HDR teams that have reported through commercial and other ones that have reported through Medical Affairs. And in my mind, Medical Affairs has always been the bridging function between medical and and commercial, you know, you you do have to be thinking in terms of value proposition, you have to be thinking about how medical messaging is going to get translated into, you know, materials for MSLs as well as, as the sales force. So there’s always been that sort of bridging function. And we always have to keep sort of compliance as top of mind, but what I would say the key to success regardless of whether it’s According to commercial or medical is that there has to be close understanding working relationship between those two functions. If you are going to successfully launch and market a product, I think there there can be some, some challenges if it reports to a commercial function, especially around things like scientific publication, which which I think scientific publications squarely falls into a Medical Affairs realm. But what I have seen is it can work successfully either way, as long as there is a close, compliant working relationship between the commercial and medical functions.

Garth Sundem   30:40

All right, let’s leave it there for today. David,Tracy, Miriam, thank you very much for joining us. To learn more about how your organization can partner with OPEN Health visit OPENHealth.com. MAPS members, don’t forget to subscribe. And we hope you enjoyed this episode of the Medical Affairs Professional Society podcast series: “Elevate”.