Today, regulatory approval doesn’t ensure anymore, that patients benefit from new therapies. As statisticians, we also need to ensure access and reimbursement for new treatments in the different markets around the world.

The process to gain this access and reimbursement in Germany comes with very specific challenges. Yet, due to the large impact of Germany on other countries via the complex reference pricing system and the size of the population of Germany, we must understand these topics.

Carsten Schwenke gathered experiences across therapeutic areas with many companies since the start of the new process in Germany. This makes him the most experienced and best connected statistician in the world for this topic.

By listening to this interview, you will

  • get an understanding of the importance of the HTA process in Germany,
  • learn about key processes and stakeholders to reach successful reimbursement,
  • get an overview about common challenges, and
  • learn when and how to address these issues.’learn when and how to address these issues.
  • In this episode, we cover the following questions:
  • Why do we need a value dossier in Germany, when we launch a new medication?
  • Who are the key stakeholders in the AMNOG process?
  • How does the process look like from a high-level perspective?

  • How is the evidence provided to regulators like EMA different from the analyses provided to GBA?
  • What are the typical problems, many companies struggle with and what are your recommendations to address them?
  • Many people are familiar with the NICE process in England or the ICER in the US. What is different in Germany?
  • Where can people find further information about this process?

Further resources for you about the German system and this episode are:

Carsten Schwenke

Transcript

Getting access for patients to new medications in Germany – the biggest challenges in the HTA process and how to address them: Interview with Carsten Schwenke

00:00
You are listening to the Effective Statistician episode number 34. Getting access for patients to new medications in Germany. The biggest challenges in the HTA’s process and how to address them. An interview with Carsten Schweinke. Welcome to the Effective Statistician with Alexander Schacht and Benjamin Piske. The weekly podcast for statisticians in the health sector designed to

00:28
improve your leadership skills, widen your business acumen and enhance your efficiency. We are creating an online course for improving your leadership skills as a statistician, even if you have no direct reports. So if you’re interested, register your interest on the homepage, thee slash course.

00:50
In today’s episode we’ll talk about a very very special case for HTA submissions, the HTA submissions in Germany. These are really really important to master because not only is the German population a very very big one, it’s for many indications one of the biggest markets in the world, there’s also a very very complex system in terms of pricing across the world.

01:20
and lots of the different other countries reference the German price to get to their price. So the German price has indirectly an impact on lots of different prices of medications around the world. So you will get an understanding of the importance of this process, you will learn about the key processes and stakeholders.

01:45
you will get an overview about common challenges and learn and how to address them. This podcast is created in association with PSI, a global member organization dedicated to leading and promoting best practice and industry initiatives. Join PSI today to further develop your statistical capabilities with access to the special interest groups, the Video on Demand content library, which actually has very, very nice things for the episode today.

02:15
free registration to all PSI webinars and much much more. Visit the PSI website at PSIweb.org to learn more about PSI activities and become a PSI member today.

02:31
Welcome to another episode of the Effective Statistician. And I’m here again with my co-host Benjamin Biesger. Hi Benjamin, how are you doing? Hi Alex, I’m very well, thanks. And we are actually coming out of just a PSI one day event about real-world evidence. And one of the big topics was also how this is applied in HTA and in different areas. We had representatives from different HTA bodies.

03:01
including ZEQUIC and of course lots of discussions as we had this real-world evidence day here in Germany were about the HTA submissions here in Germany and as such we have an expert as a guest today Carsten Schwenker. Hi Carsten, how are you doing? Hello, I’m fine. Hope you did. Okay, so Carsten maybe you can explain a little bit about what you’re doing and what’s your role and

03:31
experience in the German system? Sure I can. So my background is statistics, so I studied statistics and then worked for about 10 years in the pharma industry, mainly in clinical development. And then since 10 years I’m an independent statistician, work as consultant for pharma industry. And this mainly in the HTA process in Germany since 2011.

04:00
so-called Amnock Process was invented. And the Amnock Process is some sort of assessing the evidence so that the decision makers can decide on an additional benefit compared to a comparator which is chosen by the authority and then

04:22
when you do have an added benefit, you can negotiate a higher price compared to the standard of care. And the standard of care is chosen by the so-called Federal Joint Committee, which is a committee that also decides on the additional benefit. And then there’s another player, which is the so-called EQIC. It’s the…

04:45
Scientific Consultancy? Yeah, it’s an independent institute to assess from the methodological point of view the dossiers which you have to submit. And a dossier for the HDA process is somewhat similar to what you submit as CTDs to the e-mail, for example. So you also have five different modules.

05:11
but the content is really different. So what you have to do is to work on the clinical data you have. You have to provide evidence that there is additional benefit. And that there is additional benefit depends on whether you have direct data compared to the GBA or Federal Joint Committee chosen comparator, or whether you need to have some sort of like indirect comparisons.

05:41
where you then provide evidence to show the additional benefit.

05:46
So I’m a little bit new to the process. I haven’t had many exposure to it. So maybe can we just go a little bit like a step higher and like describe the overall process a little bit more for everyone also the non-German statistician listening. So what are the steps or what is the you know from a higher perspective the high level steps for the process. I mean you already mentioned a lot of you know stakeholders and so we get to this a little bit later but for now. Yeah, maybe the whole process looks like

06:16
that the timelines are straight and what you need to do is to submit a dossier with all the clinical evidence at the day you get the approval. Well, approval in terms of you get the approval by the email, then you have some time to announce this approval to the German authorities.

06:46
and then the clock starts. You need to submit within one month after the approval. Then the EQIC has three months to assess the dossier. Then there will be a three week time period where you can…

07:07
make your points in a written statement and then two or three weeks after you have submitted your written statement there will be an oral hearing and about six weeks later you get the decision by the GBA. But the point is these times are really strict. So you have to submit.

07:30
within this time period otherwise they will disregard your dossier and disregarding the dossier would mean that you don’t get additional benefit and therefore no premium price and this is really a challenge especially for the biostatistics groups since it is not sufficient to just provide all the analyses which are provided in this clinical study report the CSR you have to do much more than that.

08:00
You have to do more analysis in different ways. Sometimes you have to do analysis on subpopulations, especially those populations which fit to the label, to the indication. It is about showing all these endpoints and here at the patient relevant endpoints.

08:28
in a certain way so that they are accepted by Equig and GBA. And there you need to provide all these analyses, which means that usually you start about 12 months before you submit the dossier to work on the dossier. So it’s more or less the same time that you start working on it as you submit to email. Well, that’s actually the latest point where you should start.

08:55
It takes at least a year to actually prepare the value dossier. Exactly. And the average amount of these dossiers are…

09:07
Well, the module one is a summary of all the modules, two up to four. The two is explaining the mode of action of the drug and how it works. The three would be the prevalence, incidences, showing which comparator is appropriate, all these things, the costs.

09:32
where the statisticians are usually not so heavily involved, but the module 4 is a big one. And the module 4, there you need to provide all the evidence. And the module 4 is on average, well, in a range of 500 to 3,000 pages, full of documentation, full of tables, full of figures, full of text.

10:00
where you provide all the evidence and this is then assessed by eQUIC. And to fill this 2000 pages you need to be really prepared to have all the resources already in place that someone can do all these analyses to then put into the dossier. And at one point to have in mind this dossier is actually in German language.

10:29
Yes, it’s in German language, the whole process is in German language. So you are lost if you don’t speak German. And this is also some issue for reviewing the dossier, since if your headquarter is in the US or UK and nobody speaks German, you…

10:49
should not start translating 2000 pages into English and then get back all the review comments on the English language, which doesn’t help for the German language since it’s not a word-by-word translation. It’s all also about strategy. So you have to think about what was done in…

11:15
former procedures, former dossiers, what you can learn from these and then what to put into the dossier since the dossier is not only aimed for the GBA but you have different stakeholders. You have the GBA, sure, who assesses the dossier from a political point of view. Then you have the EQIC who assesses the dossier from a methodological point of view. Then you have the clinicians.

11:44
in the medical societies who…

11:49
somehow are addressed since they want to see how the drug works. You have other stakeholders like patient representatives who need to be convinced that the drug is good. So you don’t write the dossier for one stakeholder but for a couple of stakeholders and you have to somehow convince all of them which is a challenge. Especially now that since you for example

12:19
the economic…

12:22
side of the of the dossier. So I mean you need to work together probably quite closely than with other stakeholders within the company like health economists and Yeah, well whom you need is first of all regulatory affairs since if there is any change in the label if there’s any change in the timelines if there’s any change in the whole submission process to EMA you need to know in advance or quite early

12:52
early when the decision comes out. So you need to get all the regulatory documentation like the day 80, day 120, day 150 reports. Also you need to send the dossier as well. You need to provide these but also if there’s any change you need to know since sometimes you need to re-analyse all your data since the label looks different. You have a different

13:22
which is covered by the label, and then the total population.

13:27
doesn’t work anymore so you need the analysis for a certain subpopulation and this is really a mess if you don’t have enough resources to do this and this needs to be known by the statisticians who program the analysis since they need to know that there might be the case that they have to rerun so they need to set up all the programs that this can be done easily

13:57
So just as an example, it could be the case that you have run your study in a population that includes various pre-treatments and then the label basically in the end says, oh it’s all approved for these four pre-treatments but not for the fifth one that you have also in your study.

14:27
population and then you basically need to rerun all your analysis on the 75% of the population. So you need to have processes and resources in place to actually handle these kind of last minute situations because it could happen very, very late in regulatory discussions. Yes, and also sometimes you need to recalculate within this three week written statement period.

14:56
They say, well, this population doesn’t fit so much. We want to see the analysis for a certain subpopulation. Then you need to rerun it. Do you use a QC? Do you put it into a document? Have that all in German? And this was in three weeks, including review within the company. And this is a challenge. I believe it is.

15:21
And actually I had the question on my mind to ask where your role as expert or consultancy comes in, but it’s always so everywhere basically. My role is more or less in the first place helping with the strategy. So to review what is there, so all the evidence which is available, to review what is the

15:51
does a comparator fit to the comparator of the GVA? How can this study be sliced down so that at least the subpopulation fits to the label at the end to check whether there needs to be indirect comparisons if we need anything else than to set up this analysis plan?

16:16
then I very often work as translator between the market access department and the global biostatistics department to explain that all the analysis which the market access requires is really a requirement by GBA, so it’s not fun, but we need to have that, otherwise the dossier would be incomplete and incomplete dossier would mean no additional benefit.

16:44
and that we want to avoid. And then…

16:47
Usually I accompany the whole process. So the C writing, we also do sometimes the analysis since we have all the programs in place so that at the end of the day we can transfer the ADaM data sets into module 4 compatible tables so that you just need to copy and paste.

17:17
to set up a questions and answers document where I support. So what are the issues? What are the obvious issues? What are the not so obvious issues? What would be the answers? Which answers to be put already in the dossier? Which to keep for the written statement? Which to keep for the oral hearing? And also to support in the simulation of the hearing.

17:43
and in certain instances also participate in the oral hearings, sitting there as the methodologist in the hearings and then fighting for the product and the additional benefit.

17:58
Just stepping back, we talked about GBA, which is actually the German abbreviation of the Federal Joint Committee in Germany. Gemeinsamer Bundesausschuss. And GBA is actually a committee that consists of different stakeholders. Can you explain a little bit what are these different stakeholders and how that then works at the oral hearing?

18:28
The GBA consists of three independent chairmen. There is the chairman, which is Professor Hecken. He is the independent one and there are two others, independent ones. Then you have the boards, which is on the one side. You have the SIG funds, which have a vote and you have five of them. So five votes for the SIG funds.

18:58
and they want to see that there is additional benefit since it has a budget impact. If they give you an additional benefit, you get a premium price, so the expenses will increase. On the other side, you have the physicians, so the institutional medical societies, and they want to have good products on the market.

19:26
at a cheap price since if the

19:31
health system pays more on medications there’s less for the physicians sure uh… but whether that they they have in mind uh… they want to see a good evidence and they want to see that the evidence which is provided is profound and solid so that you can really claim additional benefit and on that side you also have five

20:01
have 13 votes. The point is in many cases there is balancing out. So on one side the sick funds, on the other side the physicians. So it’s up to the independent chair to decide. And so you need to convince also the independent people. So the majority is enough to get not… Exactly.

20:31
And then you have as a non-voting member, the patient representatives who have as… They can speak up, but they don’t have a vote, but they can influence. And in the oral hearings, you have the key opinion leaders from the medical societies who also can speak up, don’t have a vote, but can influence.

20:57
So overall, it’s at the end of the day, always the question, is there really an unmet medical need or is it some Me2 product? Is there good evidence in terms of direct evidence and are the endpoints patient relevant?

21:18
And for example, progression free survival in oncology is not seen by GBA as patient relevant. Patient relevant would be overall survival or quality of life or safety. And at the end of the day, you have to provide data on four end point dimensions, which is mortality, morbidity, quality of life and safety. And you should provide data on all four dimensions. And in many cases, you don’t have good data on quality of life.

21:48
pity since it’s so important in the whole process. So it improves now with the new studies, but still we are not there where we need to be. And that’s the good thing if the clinical development statisticians know already about the HTA process since they need to fight for good data so that at the end of the day in the dossier we can present good data.

22:18
So what does good data mean? So obviously that is after you have achieved regulatory approval. So you could just argue, well, you know…

22:31
The EMAR already said you had good data, so what kind of other good data do you need to get here to be successful here? Because obviously it’s really important. Germany is not only lots of people, lots of patients to be treated, but also in terms of the overall economic benefit is Germany is a reference price country for lots of other countries.

23:01
it’s really important from that end as well. It is what the data you present is slightly different which you present to EMAR compared to what you present to the GBA. Since for the GBA the relevant data is the data of all the patients who were treated within the label.

23:23
for email, they look on, for example, for safety on all studies you have done, also on studies with different doses, different schedules, different patient populations. They check for any signal in AEs, right, in the GBA or in the UMNO process, to be general. They want to see that the patients who are treated within the label…

23:51
do not have any harm with regard to adverse events or you may even show some additional benefit in adverse events. So you may gain an additional benefit just by showing that you are better in adverse events and not better or at least not worse in efficacy and quality of life. But it’s really hard to show additional benefit in safety compared to placebo. Yes it’s well.

24:21
It may happen. It may happen especially when you treat symptoms and when you collect data which are not so easily differentiable symptoms and adverse events. So if you treat diarrhea and you also collect diarrhea as adverse event, you have both in your data.

24:46
At the end of the day for the GBA it’s not so important in which end point dimension you have the additional benefit. If you can show the additional benefit in any of these dimensions and no harm in the others you still get the additional benefit. And this is really a matter of the overall assessment of all the benefits and harms you have in the different end points.

25:16
logical stringent as the assessment by end point. So by end point there are rules how to assess the amount of additional benefit.

25:29
Maybe I should first explain the two dimensions how the GBA assesses the additional benefit, which is the amount, so how much additional benefit you have, and how certain, yeah, effect size, and how certain you are. So whether the evidence you use has a high evidence or it’s a low evidence. And at the end of the day, these two dimensions…

25:58
you assess for each of the endpoints and then at the end of the day you make an overall assessment, a holistic approach so to say, to say whether overall there will be an additional benefit and how certain you are that this benefit is there and so you at the end get to the decision.

26:24
In terms of the comparison, I think that is very often kind of a matter of debate in terms of many of the phase 3 programs are placebo controlled and my understanding is you need to have an active comparator that represents the…

26:48
a relevant comparator for the GBA, which is usually not placebo but another active treatment. So it’s not about kind of showing you’re better than placebo, it’s about showing you’re better than another active compound, usually. Well to be more general, it’s about standard of care. And the standard of care could be…

27:16
medication, it could be non-medication. But at the end of the day it’s really about what is the standard of care at the moment in Germany and this is usually chosen as the comparator. It needs to be approved in this indication. It needs to be established. It needs to be hopefully in a good S3 guideline.

27:45
then you have a high probability that it is at least also chosen as a comparator, but in many cases it’s…

27:54
even not a single treatment they chose, but it is something like physician’s choice. So there are a couple of treatments which you could use and there is no clear algorithm in the guidelines which one to use in which scenario and then you need to show compared to physician’s choice or patient individual therapy that you have an additional benefit.

28:24
and usually the studies are not set up in this way. There are certain studies in this way, but not too many. But this is one of the learnings of the AMNO process. When you set up the phase three trials, your pivotal trials for submission to the regulatory authorities, you need to think about the comparator and which one to use. And as these are usually global.

28:54
projects. Some comparator has to be chosen and this is not necessarily what you would choose in Germany, but it should be a comparator so that you are able to do at least indirect comparisons in a good way. So you need to use a comparator where you have good data at least so that you can somewhat translate and do the indirect comparisons.

29:23
How do you as a company find out what is the relevant comparator of choice of the GBA? You can ask for an advice meeting, so you get advice by the GBA. This implies that you know the indication.

29:42
or at least the proposed indication in the submission since it takes a while to get this advice meeting so it usually takes 10 to 12 weeks from requiring such an advice meeting up to the decision so when you get the data or the announcement from GBA which the comparator is usually in most cases it’s quite clear

30:12
since the guidelines are quite clear or there is no other treatment so it is best supportive care and this happens many cases in late-line oncology trials where you don’t have any standard treatment anymore. The guidelines say well try to get into some clinical study and there it’s just best supportive care.

30:39
But in those cases, it’s also in the study, usually best supportive care plus placebo. So in most cases, it’s quite clear there are cases where it might be challenging since you need to ask for this advice meeting within these three months.

31:00
already. You work on the data, you have a hypothesis what the comparator is, but when you get the comparator decision, then after three months and it’s completely different to what you have expected.

31:14
then you start from scratch with new analysis, right? Since you have to check whether you have data for this comparator if you need to run inter-act comparisons, you may slice down the study population to make these studies more similar, or these issues which you have with inter-act comparisons. I was wondering, you mentioned that the GBA is assessing the certainty and effect of…

31:44
the data of the results, so how does it quantify the price? So what is the way of determining the price itself? Is there any guidance on how this is done? Well, this is a good question with regard to is the price already discussed in this environment and indeed it’s not.

32:14
It’s a two-step approach. The first step is to define the additional benefit or to come to the decision on an additional benefit based on the evidence. And then the GBA is out and you just negotiate the price with the SIG funds, but the price with the SIG, or the board of SIG funds.

32:38
and there the basis for these price negotiations is the decision on the additional benefit.

32:46
And then there are also other points which come into account, which is European reference price, prices of similar drugs in the same indication, et cetera. But this whole package of negotiation is not within the GBA process. It’s a second step. All right.

33:11
Yeah, I think that is a really, really important point. So it’s very different to lots of other areas like NICE or where you have directly a health economic model and you look into these kinds of things or budget impact model, that’s completely off the table. And I think the important point is you need to have…

33:35
at least a non-quantifiable minor at a benefit to have the ticket to go into the price negotiation. Because if you don’t have that, then you’re not entering the price negotiation. Am I right? In most cases you still enter the price negotiations, but you have difficulties to get a premium price.

34:00
Let’s assume you have as comparator a good drug which is already on the market. And this good drug has a high price. What the rule is that if you cannot show an additional benefit you get a price which is not higher than the comparator. But if the comparator has already a good price the aim could be to get along with no additional benefit.

34:29
and then in the price negotiations have a good anchor for your price negotiations since the comparator is with high price

34:39
Well, this doesn’t work if you have several comparators from which one is the high price comparator but you also have best supportive care which is cheap. Since best supportive care always also belongs to your patients since well, with the treatment with your drug doesn’t mean that they don’t get…

35:07
any best supportive care drugs anymore. So best supportive care is somewhat the basis and then you compare your drug price against placebo, so nothing. So, well, price negotiations, it’s really a separate topic. I’m also involved in this, but…

35:27
We hear now talk about the first step, where all the statisticians from clinical development are also involved. And there, it is really that in many cases, you also need to run analyses which were not published anywhere else, like subgroup analyses for safety.

35:48
So you need to run subgroup analysis on all the safety categories like patients with adverse events, with serious adverse events, etc. which were nowhere published up to that point. But GBA wants to see that. They want to check whether there is any signal for a greater harm or for a lower harm. In any of the subgroups. By the way, speaking about subgroups, what kind of subgroups are we looking at?

36:18
Usually you need to provide analysis for all the subgroups which you defined in your study protocols but not only for the endpoint where you defined it in the protocol but for every endpoint. So if you have, let’s say, and I had that example, you have

36:43
20 endpoints and you have 30 different subgroup definitions, you end up with quite a lot of subgroup analysis. The point is you need to provide all this and it’s a huge effort to provide all this. It’s a huge effort to display these in the dossier. It’s a huge effort to…

37:09
come to a storyline, since you have to think about a storyline, how to put all these information pieces together to come to a good story. And this needs to be presented in a way that somebody from the GBA can understand this.

37:30
and now how to summarize 2000 pages of evidence into let’s say a one-pager.

37:39
Well, I think one of the key things that I have seen there is that you look into the p-value of the interaction test between the subgroup variable and the treatment and you put this p-value, these p-values matrix of endpoints times subgroups into a big kind of table so that you can at least see are there kind of any patterns.

38:09
Is it always the same subgroup that has a treatment effect across all the different possibly related endpoints or is there something, one endpoint that has across all the different subgroups something. So I think that’s already a good starting point to get a little bit of a feeling of it and to kind of possibly develop a story or basically see, well it’s completely at random.

38:39
that are significant maybe a red and you see it’s kind of completely scattered over. Yeah in most cases you just see a random pattern so you don’t see any real patterns but you also have to check whether there is a biological rational for this. So is there any medical knowledge about this?

39:05
subgroup category as effect modifier or not since if there’s nothing known but you see a gender effect in your data for one endpoint it’s most probably really a random effect rather than really something in terms of that there’s some

39:30
also require subgroup analysis that you need to do? Well, you definitely need to provide subgroup analysis on gender, age, uh… severity of disease and…

39:42
region, so in terms of countries. But obviously if you have a study in prostate cancer, gender is not so informative, but in all other cases you at least need to provide these four, even if they were not defined a priori.

40:05
but you need to provide also all the a priori defined subgroup analysis and this is really a huge amount of analysis you need to provide and i think that it’s really really important if in the protocol you have very good

40:22
rational for why you did the analysis and you have clearly defined kind of, for example, cut points on continuous end points and not something like, oh, we divide by the median of some continuous variable and we look into high ups and the low ups.

40:44
and then possibly you have different studies and for each study you have a different kind of cut points and then it gets really, really nasty.

40:54
Yeah, absolutely. But also, when you set up a trial, you should think about whether you need the subgroup definition for this study also. In many cases, when you check the protocols for the phase three trial, and then you ask back to the clinical team why this and that subgroup is still in, well, in many cases, the answer is, well, we’ve done that in the phase two trial.

41:23
and we just copy and paste it. But you should think about whether you really need this subgroup analysis and whether you can do something, how to interpret the results at the end of the day. Since you need to report it, if it is a priori defined, and then you should be able to somewhat interpret the results.

41:49
So what could be kind of the drawback if you have too many subgroup analyses? What could happen in the process? Well, what could happen is that you do see some random pattern which is unfortunately not looking random.

42:11
So you end up with the signal which is not really there, but it’s just because you have looked at 900 different subgroup analyses and you will find some of these to show strange results. And then you need to argue again these.

42:30
And it could be that maybe then you get additional benefit for just one category of the subgroup but not for the other. Yes, could happen. So what…

42:44
very often happen is that they either define subpopulations based on the indication. So if your indication is treatment of first line patients and second line patients, GBA will define different comparatives for the first line patients as for the second line patients. So you have to slice down your study population into first line patients and second line patients.

43:12
If you just have second line patients and EMA gave you the indication for first line also, you don’t have any evidence for the first line patient, so you don’t get any additional benefit. It happens. The other point is if you have a potential effect modificator. Let’s assume you really have differences by age.

43:35
then you may end up with an additional benefit for the younger but no additional benefit for the older patients, which has no impact on the ability to prescribe the drug and get reimbursed.

43:53
But for the price negotiations, which is a mixed price across all the sub-populations and sub-groups, you may end up with a lower price just because you don’t get a higher price for the elderly, you get a higher price for the adults, and depending on the amount or rate of patients younger and older, you get a different price.

44:21
and

44:21
Alexander mentioned before already that the process, I mean we described it in many details now but you already mentioned NICE for example. What are some other key differences, I mean we talked about the price negotiation at the end but what are the key differences between other countries in the process that we look into in Germany? The main difference between the UK or England and Wales was NICE and Germany was the GVA is that…

44:51
And here we do have this two-stage approach. One is first is setting the evidence and then negotiating the price. In the UK it’s one step. The other point is here you don’t have the economic evaluation. It’s just in exceptional cases. So if in the price negotiations you don’t come to a price.

45:18
you can go to an arbitration board. And within the arbitration board, it may happen in future sometime that there will be an economic evaluation. Doesn’t happen for the last three hundred cases, but it may in future. In the UK you have this economic model, which is the basis for the the whole assessment. So it’s a completely different approach. Especially with the EQ5D.

45:48
which is the basis for the UK assessment. And in Germany it’s not accepted as patient relevant endpoint except for the visual analog scale. But this is not quality of life but it’s morbidity. So it’s a different dimension and a different way of looking at it. And it’s a good example how different the processes are.

46:14
And also the time pressure and so on, this is kind of similar between the countries. So just looking from the resource and planning objective, or do they have like looser time frames to process the submission? Well, in the UK it’s a little bit less strict.

46:33
in germany you have really strict timelines and you have to fulfill this these timelines otherwise you lose uh… in the u.s. is completely different system we should not like it that they do directly negotiate with medicare was medic-aid was said different sick funds you have a direct conversation you also have to provide data you have to provide uh… models budget into impact is that right

47:03
It’s a really completely different system. One of the main differences is also the system in Germany takes care of 90% of the population in Germany. It’s really, really important. If you fail on it, you fail in Germany. It’s pretty, pretty simple. And you fail in Europe. And you fail in Europe due to the reference pricing. Exactly.

47:33
And you just mentioned a work count of about 300 cases. That’s about the number of dossiers that have been… Procedures up to now, yeah. In what, seven years? Okay, 11. Where can people find further information about this overall process in terms of documents, the dossiers that were handed in, things like that? Well, if you are able to read German.

48:00
then you go to the homepages of GBA in a quick.

48:05
since all the templates or the methods papers are usually provided in German, there is an abbreviated report on the methods in English from the EQIC. So that’s the methods guide. The methods guide. The EQIC complex. Exactly. Then, there are a couple of workshops all along, especially at the biometrics conferences of the International Biometric Society.

48:35
German region. There’s always a workshop on HTA and EQIC methodology. There’s also the GMDS for example where there are workshops also in other countries, societies, biometric societies, the PSI who sometimes do workshops on this issue.

49:05
But, well, and then there’s ISPOR. So the next ISPOR is mid of November in Barcelona, where there will be certain presentations on this issue.

49:19
In terms of PSI, there’s actually one really nice resource for the PSI members. Carsten did a really nice 3 case series on the overall system, the slidesets and all these kind of things and you can find that on the video on demand platform on the PSI homepage for PSI members. And I think one important thing is, you know, all these dossiers.

49:49
so the modules 1 to 4 are all published on the GBA homepage as well as the

49:59
audio company, the reviews from the EQIC, the statements from the different reviewers, the revision from the company as well as the transcript from the oral hearing, all of that is actually available there. So it’s pretty much data that is actually out there that you can look into or at least that your German speaking colleagues from the market access department can have a look into.

50:29
explain what’s in there for you. And this has an upside and a downside. The downside is obviously that, well, it’s public so everybody can look into the data. The upside is everybody can look into the data. And this is especially helpful if you need to run indirect comparison against some product which…

50:55
gone through the process since you have the module 4 with all the data already set up in a way you need it for your dossier and then it’s easier to run the indirect comparisons. And you can also more easily check whether the studies fit together since you find much more information than just from the…

51:18
publications on the other trials. So this is really a good thing. On the other hand, as Alexander mentioned already, in the Module 4 at the moment you provide the subgroup analysis only for those subgroups where there is a significant interaction between subgroup and treatment group.

51:44
So you have again a limited amount of data you can use for the intercomparison and you may not pick the subgroups or the subgroups which are important. On the other hand, if all the subgroups would be presented and this may be in the future,

52:06
then you need to run all the analysis on all the subgroups and also on all adverse events on a preferred term and system organ class level, which then ends up with a huge tremendous amount of data you need to analyze. Thanks a lot for the nice talk, Carsten.

52:33
So just one last thing is how do people find you in case they do need some support? You just go to my homepage www.scosses.com

52:46
which is the easiest or you just search my name in Google and you come to the homepage or you just go to the links in the show notes of this episode which I think showed kind of it’s a very very long process there’s a it’s very strict from a process point of view there’s clear kind of guidelines on what to do but on the other hand you also need to have a very very good strategy

53:16
to go through successfully through the process. And it really is about good collaboration with your German colleagues to understand where all the pitfalls and yeah, start with that rather sooner than later. And the major point is having a good strategy and a good storyline at the end of the day. Otherwise you’re lost.

53:43
Thanks so much. Thanks a lot. Thank you.

53:48
This show was created in association with PSI. Thanks for listening. Please visit thee to find the show notes and learn more about our podcast to boost your career as a statistician in the health sector. If you enjoyed the show, please tell your colleagues about it.

Join The Effective Statistician LinkedIn group

This group was set up to help each other to become more effective statisticians. We’ll run challenges in this group, e.g. around writing abstracts for conferences or other projects. I’ll also post into this group further content.

Join Group

I want to help the community of statisticians, data scientists, programmers and other quantitative scientists to be more influential, innovative, and effective. I believe that as a community we can help our research, our regulatory and payer systems, and ultimately physicians and patients take better decisions based on better evidence.

I work to achieve a future in which everyone can access the right evidence in the right format at the right time to make sound decisions.

When my kids are sick, I want to have good evidence to discuss with the physician about the different therapy choices.

When my mother is sick, I want her to understand the evidence and being able to understand it.

When I get sick, I want to find evidence that I can trust and that helps me to have meaningful discussions with my healthcare professionals.

I want to live in a world, where the media reports correctly about medical evidence and in which society distinguishes between fake evidence and real evidence.

Let’s work together to achieve this.