The Current State Of EU HTA: Large Challenges Ahead!

The Current State Of EU HTA: Large Challenges Ahead!

[00:00:00] Alexander: Welcome to another episode of The Effective Statistician. And today I have once again, Stefan Walzer here from Mars with me on the show. [00:00:10] Hi, Stefan, how are you doing? 

[00:00:11] Stefan: Very good, Alexander. Thanks for having me. And obviously it’s great to be back. 

[00:00:16] Alexander: Yes. So if you don’t know about [00:00:20] Stefan, he has been on the show already multiple times, has been part of conferences from myself, and so but still for [00:00:30] those.

[00:00:30] Alexander: Who doesn’t know you, maybe you can give a very short introduction on what you’re doing and where you’re currently up to. 

[00:00:37] Stefan: Absolutely. Perfect. Thanks. Thanks for that. So [00:00:40] I’ve been working in the area of Market Access Health Economics Pricing for more than 20 years. I was working in consultancy, have had as well, quite a good number of years in the industry.[00:00:50] 

[00:00:50] Stefan: And for a bit more than 11 years, I’ve been running my own consultancy. We have had. Bigger focus in the last years on the German speaking markets. So Germany, Austria, and [00:01:00] Switzerland, but nowadays I think also with all of those different language models and I, and AI kind of maybe just a height question mark, I think we have as well been moving a bit [00:01:10] more into, as we call it market access 4.

[00:01:12] Stefan: 0, but I think overall, and I think that’s probably what we have as well, but the the, the, the kind of a connection is for sure market [00:01:20] access is not only about, let’s say the economics of it. But it has a lot to do obviously with the clinical part, hence with statistics, with statistics, sorry, of [00:01:30] course, as well.

[00:01:31] Alexander: Yeah, yeah, definitely, definitely. And just scroll back in the episodes, you’ll definitely get some [00:01:40] insights about that, even though you might not work directly in this HTA area. So also if you work in phase one, two, [00:01:50] three, then you will definitely benefit from these things as well too. I don’t understand why certain things need to happen in development in a certain [00:02:00] way.

[00:02:01] Alexander: And that is actually getting more and more important. And that’s actually the topic of today. What is currently happening [00:02:10] within the EU HTA area? 

[00:02:13] Stefan: Yeah. I mean, I think we probably need to differentiate a bit, right? I think one thing is obviously what is happening in the individual [00:02:20] countries, but I think with also the kind of, let’s say difficulties around the economies, struggling economies, obviously, let’s say payers across those countries are looking [00:02:30] for cost savings, meaning trying to as well, bring further the prices down.

[00:02:34] Stefan: And the price is down obviously as well, always the question, how could you do that? Hence, they are also [00:02:40] trying to get even more strict. On the kind of requirements, especially from a clinical and statistical perspective. That’s one side, right? On the other side, we’re [00:02:50] obviously as well entering into a new era.

[00:02:52] Stefan: We will get into the so called European Joint Clinic Assessment which will start early next year. So it’s in the first quarter of next [00:03:00] year. And some of those indications which might be then launched after that, firstly need to go through that so called JCA which is especially oncology, rare disease [00:03:10] areas, the advanced therapy medicinal products, ATMPs, and also vaccines and antimicrobial agents as well.

[00:03:16] Stefan: So it’s a smaller kind of group. Interestingly, for me as [00:03:20] well, oncology, okay, I could maybe understand that it has a bigger kind of impact. But I mean, thinking about 18 piece and the kind of sample size kind of issues sometimes what you have, [00:03:30] it might get a bit tricky as well already on a pan European level before you would even enter into then the kind of real submissions, meaning the negotiations on a national [00:03:40] level.

[00:03:40] Stefan: That’s a current kind of, let’s say, big discussion, the hot topic probably across Europe.

[00:04:32] Alexander: Yeah, so European Union things are happening, so that means that does not [00:04:40] include the UK and England, which is nice, isn’t it? 

[00:04:43] Stefan: Exactly. Absolutely correct. I mean, due to Brexit, I think the UK is basically out of that component, [00:04:50] meaning, let’s see, the complexity might even increase when you are coming or when you are coming outside of the European Union, right?

[00:04:57] Stefan: I mean, if you are maybe US company and want to, let’s say, [00:05:00] concur the European let’s say environment, the different nations you have on the one side, you have the UK with the specifics on the regulatory side. And obviously then as well with UK nice, would you as well, just [00:05:10] said. As well with respect.

[00:05:11] Stefan: For example, the cost effectiveness, which is quite complex already. And then I think on the other hand, you have then the bigger European Union with now a [00:05:20] pan-European clinical assessment, firstly, which is then basically coming before you would need to submit still to the national agencies and some in some countries, even [00:05:30] on a regional and or local level.

[00:05:32] Stefan: So it’s getting, let’s say, a bit more complex potentially. We need to see, I think we still have a couple of question [00:05:40] marks. If potentially that kind of further layer might even make the life a bit easier, I think it could very well be, I think if we have spoken with some payers, [00:05:50] probably more from some smaller countries in the European Union with not so much manpower, for example, like Germany or France.

[00:05:57] Stefan: Then this could obviously help because then they would just [00:06:00] say, look, we wait for the European JCA, which is happening before their submission. And then we take that as a basis for the negotiation that could potentially speed up the timing until market [00:06:10] access, meaning a price agreement. On the other hand, obviously there are also, let’s say some critiques.

[00:06:15] Stefan: As people might just say, you know, it’s just another layer and you would still need [00:06:20] to obviously submit kind of further analysis, for example, for Germany, for France, for a couple of other important countries. And ultimately, if you maybe mix everything together, [00:06:30] why should maybe as well, the industry have an incentive to, for example, get an agreement with a small country, for example, with, I don’t know, maybe say Poland, which is [00:06:40] not so small, but still, let’s say smaller than, for example, France and Germany, maybe even with a lower price.

[00:06:45] Stefan: So I think the kind of order might still be the same as we now see, and that’s a bit the kind of [00:06:50] question mark. And I think it will be really interesting to see what is happening in the next two years. 

[00:06:54] Alexander: So just from a timing perspective, so what’s currently [00:07:00] happening is you more or less start with the HTA submissions around the time of the European [00:07:10] approval.

[00:07:10] Alexander: Yeah. So in Germany, for example it usually is a couple of weeks after, after the approval where you need to submit your [00:07:20] HTA dossier. How will that work in the future?

[00:07:24] Stefan: Well, that’s a very good one as well. At least a theory behind, right? Is [00:07:30] that, let’s say at the time of the positive opinion by the CHMP, companies should be able to submit the JCA dossier ready. [00:07:40] The reason for that is basically very simple. And you just laid that out with a different kind of timings, right?

[00:07:44] Stefan: If you want to be ready for national submission in at least Germany, for example, [00:07:50] very close to the actual approval, which is happening normally eight to 12 weeks after the CHMP opinion, you need to have the JCA dossier ready, let’s say those two, [00:08:00] rather three months before the actual approval already is being submitted as obviously also the agency, which is handling.

[00:08:06] Stefan: The the, the JCA on a European level needs as well a bit of time, [00:08:10] right? They need time to review, to give feedback, to finalize, to finalize as well a kind of recommendation, let’s say, that this can as well be used, and that’s the [00:08:20] idea, as a basis also for the national submissions. But this is then also a bit of the tricky question.

[00:08:24] Stefan: I mean, you as a statistician have been as well pretty much let’s say, involved as well in those early [00:08:30] stages, right? A lot is happening around, let’s say, the definition also of the label. And this is happening, let’s say, around the CGP opinion, right? So how could you really make Let’s [00:08:40] say everything ready, so close to the kind of actual submission of the JCA, meaning the actual kind of approval, not approval, sorry, the positive opinion [00:08:50] of the CHMP.

[00:08:51] Stefan: Everything’s happening basically around the same time. A lot of times this might not be an issue, right? This might just be small kind of changes, but just imagine the CHMP might [00:09:00] just open a subgroup. Instead of the ITT, which have been in the, in the trial, right? Or maybe they move a, a product rather in a later line or include a later line, which [00:09:10] might as well mean that you would need further analysis against additional comparators.

[00:09:15] Stefan: So that’s a lot of, let’s say, uncertainty around it. And that I think will be really, really interesting [00:09:20] to see how the industry, especially maybe smaller or mid sized companies will react to that. 

[00:09:25] Alexander: Yeah. Or maybe there’s only, you know so those will [00:09:30] depend on certain factors. Yeah. So maybe, you know, you have two doses in your study.

[00:09:35] Alexander: Yeah. And they say, well, we approve the lower dose for [00:09:40] these patients and the higher dose for these patients. 

[00:09:43] Alexander: Yeah. Perfect example. And then see, you basically need analysis, all the [00:09:50] analysis again, where you basically have two arms, so comparator, and then so to say a pooled [00:10:00] dose up, yeah? Where the, let’s say the lower weight patients gets a lower dose and the higher weight patients gets a higher dose.

[00:10:07] Alexander: Yeah. Imagine that might happen. Then you [00:10:10] would basically need to re-run all the analysis. Yeah. You basically need to be, you know, ready very, very soon [00:10:20] into agile with these kinds of things. Exactly. Anders, a fellow statistician on LinkedIn, talked about statisticians being [00:10:30] super heroes to achieve all these timelines.

[00:10:32] Stefan: Yeah, exactly. Exactly. No, I think you probably hit the, the, the. the right kind of [00:10:40] direction, right? I think everything would be super hectic probably around the kind of one, which it has been as well in the past, but I think the past is probably just Let’s see quite easy in [00:10:50] comparison probably to the to the near future if you want to still stick to those kind of let’s Say timelines you currently have used right?

[00:10:56] Stefan: Obviously, you can as well be a bit more relaxed If you just say we first do [00:11:00] the ctmp opinion then we prepare and submit maybe even four six eight weeks later to the, to the JCA, meaning that still they need some time to review. You get [00:11:10] the approval already somewhere between, then you wait for the kind of feedback and obviously then you just maybe further prepare the submission for the national agencies.

[00:11:18] Stefan: So it’s a bit of the question as well. [00:11:20] Just keep in mind, I think politicians or the idea of politicians on the European level in order to let’s say create that kind of GAC, what it was especially [00:11:30] also to to streamline the process in order to get the drugs faster to the patients across the various countries. If that will be achieved, I’m not really exactly [00:11:40] sure. 

[00:11:41] Alexander: Yeah. How far are we in terms of knowing exactly what needs to be submitted [00:11:50] and in which forms? 

[00:11:53] Stefan: Yeah, let’s put it that way. I think a couple of more question marks are probably Already a bit more answered. I think there’s [00:12:00] a template now available somehow, I would say, right?

[00:12:03] Stefan: For the dossier. I think at the last e spore in Europe, which was mid of [00:12:10] November last year, which is roughly five, six months from now, when we just speak. And roughly a bit more than a year before the actual JCA would come into effect. I think [00:12:20] as far as I remember, I don’t know exactly anymore the kind of exact number, but the feedback from some European responsible person was, yeah, you know, we have probably [00:12:30] already achieved somewhere around one third of the tasks we needed to do before the kind of actual launch of the JCA, which is to me a bit of a joke.

[00:12:39] Stefan: I mean, [00:12:40] you know, people, companies need to prepare and, you know, they just do it now within that one year. And I would bet that not everything is answered [00:12:50] when they try to launch it. If I would maybe want to say that in the first quarter of next year. 

[00:12:56] Alexander: So that means people can’t kind of [00:13:00] completely already now know, okay.

[00:13:02] Alexander: Yeah. Next year in 2025, we will need to do these kinds of different things. They don’t even know yet. [00:13:10] What they will be asked to fill in and what kind of formats on these kind of things. So you really need to be even more agile and more [00:13:20] flexible to then adjust to all these kind of different settings.

[00:13:24] Stefan: Yeah, no, absolutely. And you know, just, just as well, keep in mind, I think in most of the countries you also have [00:13:30] the opportunity to speak with institutions beforehand, right? Yeah. You have those early consultations, and this has just been put into place earlier this year together than with the [00:13:40] joint HDA, sorry, with the joint yeah, HA a kind of process with the GPA in Germany.

[00:13:44] Stefan: But keeping in mind as well, we already have a big backlog in the German assessment. [00:13:50] Let’s say process for the consultation with the GBA already, just with the general one, right? And you could just imagine they cannot just shift and put a lot of new people as well in that kind of process and just give a [00:14:00] small additional kind of feedback there.

[00:14:01] Stefan: So if you’re lucky, you have maybe already gotten a consultation on the European JCA level with the GBA. They do it on behalf, [00:14:10] right? If you’re unlucky, maybe you don’t have one now and you maybe plan a launch in early next year. It might get even more tricky, right? Because otherwise you get at least some kind of [00:14:20] feedback.

[00:14:20] Stefan: Even that, let’s say not everything is currently being planned for, it has been decided and knowing how the DBA let’s say personnel [00:14:30] is reacting. And I think that’s, that’s absolutely correct. They basically just tell you what is a hundred percent clear, a hundred percent defined in the various regulations.

[00:14:38] Stefan: If something is not [00:14:40] included there yet, they cannot give you an answer, obviously. So it’s not helping a lot at the end of the day, potentially. Right.