The best sources for RWE that you may never heard about

Transcript:

Alexander: You’re listening to The Effective Statistician podcast, a weekly podcast with Alexander Schacht and Benjamin Piske, designed to help you reach your potential, lead great sciences and serve patients without becoming overwhelmed by work. Today, I’m talking with Anders about the best sources for real-world evidence that you may likely never heard about, so stay tuned. 

I first heard about these sources for real-world evidence a couple of years ago and I tried to have an expert on this evidence for quite some time. So, I’m really, really happy that I have now Anders to speak about Scandinavian data. And you may wonder why data from these nordic countries is so special. Stay tuned for this episode because you will learn that this is really the best source. It’s kind of a dream for us statisticians. 

I’m producing this podcast in association with PSI, a community dedicated to leading and promoting the use of statistics within the healthcare industry for the benefit of patients. By the way, there’s also a real world data special interest group, you may join that and join PSI to further develop your statistical capabilities with access to the video on demand content library, free registration to all PSI webinars and much much more. Head over to psiweb.org to learn more about PSI activities and become a PSI member today.

Welcome to another episode of The Effective Statistician. Today, we are talking about one of my favorite topics again, real-world evidence. And I have an expert today here on a very interesting area of real-world evidence. Hi Anders, how are you doing? 

Anders: Hi, Alexander. I’m very good, how are you?

Alexander: Very good. Before we dive into the topic of speaking about real world evidence from the Scandinavian countries, let’s first talk about your career up to now. What has brought you to where you are now? What about your company that you have started? 

Anders: Thank you. I’m a biostatistician by training and then I did some research within epidemiology at The Karolinska Institute. I started to work in healthcare and academia for several years in this field but then at some point I also started my own business and did some consultancy in the life science industry. And then I wanted to try how it is within industry so I joined Pfizer about more than 10 years ago. And since then I’ve been working in the pharmaceutical industry for 10 years. And from last year, I started my own company, Epistat, that works within the life science industry within this research area. 

Alexander: Awesome. So let’s talk about these Nordic Registries. When we talk about these, which countries actually are involved? 

Anders: I would say, when you say, if you include a whole Nordic countries, that’s Iceland, Sweden, Denmark, Norway and Finland. For the purpose of this discussion, I think we should focus on Sweden, Denmark and Norway and Finland. You out Iceland  because it is quite a small country, its context. 

Alexander: Yep. It’s quite small. When we think about all of these countries, it’s about 25 million people, which in these countries you would think like compared to Germany or especially compared to the US. It’s not big but just the other day I talked to someone who was working on a real-world evidence project and they had worked on these countries and also on evidence from other real world evidence sources for specific areas. And in their overall dusche, by far the largest proportion of evidence was coming from these Nordic countries. And that has to do with a couple of specific features of the Nordic countries such as that will go in today. So, if you might think like, well, ‘Who cares about these, let’s say, small countries’? Actually, from a data perspective, they are really, really big. So when we think about these Nordic countries, what makes them so special when it comes to the health system?

Anders: Yes. So yeah, across the nordics, all countries have a Public Finance Healthcare System. The tax is quite high in the nordics, however, the cost for a patient within the healthcare system is therefore quite low. So it’s very low. 

Alexander: Yeah. It’s very text and government. 

Anders: Yes, exactly.

Alexander: Yeah. The other thing is lots of these registries. And whereas very often registries, organized, let’s say by a community of physicians or by associations, this is a little bit different in the Nordic countries, isn’t it? 

Anders: Yes, I think that’s one of the key success factors when researchers are reaching out in the Nordics because we have most of them are population based which means that it’s nationwide covered most of the registries. It’s a very unselected group within the registries in comparison to other real-world evidence data sets.

Alexander: Yeah. That’s a big, big strength that you have the whole population and not just this one insurance company or things like that makes it really, really strong. Also it’s much more unified rather than every part is different. Let’s just first dive a little bit into the population registers. So what kind of population registers are there that are kind of, Nationwide? 

Anders: Yeah. So there are several of them. We have, of course, the total population registry where we have vital status on every resident in the nordics. We have the cause of death registry, where we have information on the cause of death and the date for that. Of course, we have the patient registries where we can collect hospitalizations, inpatients and outpatients information. You could also add a cost to that hospitalization of course. We have the birth registries where we have information on the birth of the baby, but also some information on the mother. Then of course we have the cancer registry and the prescription registry where we kept information on all the prescriptions on the drugs across the nordics. 

Alexander: Wow, that is quite a lot. That’s pretty cool. Now, when we look into other areas, of course, we have these data sets as well but what makes it really unique in the Nordic countries is that you can actually link these all together. How is that done? 

Anders: Exactly. I think the first is population based. The second thing is that each resident in the nordics has their own social security number and each registry collects that information. So, you are able to link at the individual level, all these data sets into a research database. So you can actually identify some of the diseases at the patient registry and then you can look at the incidence of malignancies for example. 

Alexander: Yep. And all of these registries otherwise used are not only set up for research questions, are they? 

Anders: No, no. Of course, that’s one big bucket for them to reach, but I think the idea was to understand the healthcare system, and how it works to increase healthcare on a data basis.

Alexander: Yeah. So it’s also in the interest of the overall system that the data is of high quality.

Anders: Very much, very much.

Alexander: That’s pretty outstanding. Basically you have a whole data set that was pretty much all the, you know, disposition, demographics, all the kind of information altogether at a start. And then you can add on top of that these disease-specific registries. How are these done and what kind of disease specific registries are there?

Anders: As we said, we have the population registries and these are mandatory to report into. Then we have the disease-specific registries which are not mandatory, it’s mandatory in Denmark, but not in the other countries but they include more detailed information on the diagnostic management and outcome for specific diseases. So we have for example, in oncology we have the specific lung cancer registry or breast cancer registry, prostate cancer registry, where you can actually look at diagnostic intensity, you can look at different mutations, outcome, treatment patterns. These disease specific registers can also be linked to down the registries, of course, you can really have a good detailed research database, where you can do some cool statistics on.

Alexander: Yeah, that is pretty cool. I’ve also heard that there’s some more kind of medical related data in there. It’s not only kind of the typical claims data but also as you mentioned outcomes and things like that even patient-reported outcomes. 

Anders: Yes some of the registries that are really also quite disease-specific but I’m on the registries are collecting patient-reported outcomes and also not only at baseline, they are also following the patients over time which is really important.

Alexander: Yeah. Basically, you have lots of the data that you would need for very very good observational study and also disposition data, you have the exposure data, you have the patient characteristics and you also have outcomes that you can relate it to. That’s pretty exciting, as I mentioned, makes it really unique. I wish that it would be a model for other countries around the world, including Germany. Now if I want to do some research on that and probably if your researcher and you have listened to that you already kind of get really nervous about, ‘ah, it really answers my questions using this data’. How does that work? 

Anders: Yeah. There is overall governance of course when it comes to these individual data sets so of course you need to have a synopsis study, synopsis protocol. You need an ethical approval before you can even apply for the data sets, then you can reach out to the registry owners, sometimes, it’s several owners and apply for the data. And then at the end sometimes depending on who you are, you can actually get individual data but sometimes, you could also collaborate with a zero or a research company that could do that analysis for you. Then you present it either as a scientific publication or a report in some way. 

Alexander: You mentioned the relationship factor. I guess kind of just coming out of the blue and saying, ‘I made mistakes and I work for a company’. Why isn’t the best approach for moving forward? How does it work from building up that trust and being allowed to have access to the data? 

Anders: I think if you have a good research question, you can come from your own company. But however as always it is good to start a collaboration and maybe you could identify within the academic setting, there are some interesting new research questions then you collaborate with them on that question and maybe they can help you on the research question. And also eventually, the analysis. I think it’s really good that  you need to collaborate in some way. 

Alexander: Are there any kind of typical academic institutions that you would go for?

Anders: That’s very dependent within which disease field you’re in. But the Karolinska Institute has really good knowledge within this real-world evidence efforts, of course, but there are several others across the nordics. 

Alexander: Okay. So probably if you do some research and you look for who else the typical people that work on this, you’ll find some contacts to follow up on. 

Anders: Yeah.

Alexander: But of course, people could also come to you for help, isn’t it? 

Anders: Yeah, that’s the next thing you could do. I mean you could also reach out to me at the Epistat. You want to conduct this research within the nordics and we can set up the collaboration, the study protocol ethical application, and we can also retrieve the data as a research company and we could do analysis for you. 

Alexander: Yeah. If you think from an overall timing perspective, I want to do these kinds of things, what is a turnaround time that I would need to plan before I have everything in place and also you report back from the first idea up to the report. 

Anders: Yeah, that’s also a bit tricky. Sometimes the initial phase with the contracting process could take some time, depending on your internal process within the companies. But then I think the time that’s a little bit hard to calculate these days is the data extraction time, especially now, when we have had the pandemic. The time has been prolonged quite a lot, but usually I would say that this kind of research could go within the year.

Alexander: Okay. Planning for years is good. Okay. So if you need that for your HDA submissions things like this, you should get going. Let’s say before you submit to the EMA so that you have everything in time by launch. 

Anders: Yeah. 

Alexander: Okay. Very good. That is from timing and project management and these kinds of things. Let’s give a little bit into some examples. What would be cool case studies that you could look into? So can you give me some examples that you have maybe worked on or that you have seen.

Anders: If you’re at a pharmaceutical company, I think you can do studies across the full lifecycle of a  drug because first you want to understand the disease you are working with and you can do some, I mean incidence and prevalences studies since these populations base are quiet nice to get the true incidence or the prevalence of a disease. You can understand the comorbidities, priority disease, and also post-diagnosis. You can now understand the landscape of the current treatment patterns, for example, and you can look at the outcomes such as overall survival from a natural course. I think that’s in the initial phase.

Alexander: Yeah. Now when I have a new drug on the market, how can you help me there? 

Anders: Yes. Then you could also do first of all, try to understand, how does the drug work on this market in the nordics? Is it for all indications? Is it prescribed off-label? And why is that etc? So, that’s one important factor and also look at the effectiveness, of course, in the real world setting.

Alexander: Also compared to other drugs, which is really, really good. 

Anders: Sometimes it could get quite crowded and you maybe need to do some kind of comparative effectiveness study. And also look at safety signals because as we know, all the clinical trials are quite short and yet we need long-term data on that. So look at safety signals in the real world setting. I think that is also one of the advantages here. 

Alexander: Yeah. Absolutely. And that way you can get a pretty easy setup, post registration safety studies, things like that or you can get a lot of material for working with medical affairs. There’s an endless opportunity, so to say, to work on this.

Anders: Yes. As you mentioned HDA submissions, you can always work on health economic models, populate them with these kinds of data sources, you can add costs, socio-economic variables, etc onto this. 

Alexander: Yeah. And that is especially important if you want to, for example, look into whether your track lowers the risk for hospitalization or these kinds of things, which is really hard to observe in a clinical trial based on that is not so long and that it’s usually not so big,  it’s really hard. The other point is also more harder end points. You can look into whereas in a clinical trial you have very often more surrogate markers that sets a great thing. If you think about it from a generalizability point of view, of course, it’s western world data, from your experience, how well would it be received in other parts of the world from and of how relevant this is in other parts of the world? 

Anders: I think the reputation of the Nordics is quite high across the globe. However, I think the drawback is, of course the population, especially, when you’re looking into rare diseases is given not to get too many cases, of course, but I know this is well used in the US and also across Europe, of course. 

Alexander: Yeah. From that end, I think it’s a really, really valuable contribution to your overall HDA and medical medical affairs success. And as I said before, it can even help you earlier when you for example want to understand, what is the natural course of the disease or if you want to bolster your understanding in terms of safety, these kinds of things, can make a big difference. That was a really, really good discussion about the Nordic countries and all the huge benefits it has. Just to summarize it, it is a unique opportunity to link lots of different databases together, while there is a personal identification number that way you have lots of the disposition baseline, all these kind of data together and you can combine it with disease-specific registries which can help you to have also disease-specific end points and things like that. And that all in a time span of I would say about a year depending on how fast your internal and external processes are. Recently, I’ve noticed that sometimes the internal processes of the company take long. It’s a pretty pretty cool opportunity and if you want to work together, just reach out. I think it’s a great thing. Thanks so much Anders, any final recommendation you would have for the listener on this topic. 

Anders: No. But I think I could just add to the summary that this also comes with a quite low cost, that’s also quite important because setting up a phase four started for safety is, what does it cost? This is one hundredth of that. You can get detailed data to a very low cost. 

Alexander: Yeah. I completely agree. And also in terms of timing, one year is nothing compared to setting up and running a phase four study, so I completely agree. Okay, we’ll put all these things into the show notes together with the link to Ander’s homepage so that you can easily reach him. Thanks so much Anders, that was a great discussion. 

Anders: Thank you very much, Alexander. Thank you. 

Alexander: This show was created in association with PSI. Thanks to Reine, who helps the show in the background and thank you for listening. Reach your potential, lead great sciences, and serve patients. Just be an effective statistician.