I'm Aware That I'm Rare: Rolf Berger, MD

Rolf Berger, MD discusses pediatric pulmonary hypertension treatment in the Netherlands and the challenges in clinical trials in children with PAH. Dr. Berger is a pediatric cardiologist from the University Medical Center of Groningen.

Transcript:

I’m Rolf Berger. I’m a pediatric cardiologist working in the University Medical Center of Groningen in the Netherlands, which is the national referral center for pulmonary hypertension in childhood. I’ve been interested in working in the field of pulmonary hypertension for, I think, almost 25 years now. In those 25 years, I’ve seen the developments that have been achieved in this field. Also doing research, clinical research and basic research, trying to find possibilities to improve this disease for children.

We developed in the Netherlands, I think it’s pretty good, collaboration between all the university centers which resulted in a network for a pulmonary hypertension in childhood. We have the European Medicine Agency who approves the drugs for pulmonary arterial hypertension for adults, for children, and then we have the local countries who decide about reimbursement.

In Europe, the EMA, (European Medicines Agency), has approved sildenafil for pediatric pulmonary hypertension and bosentan was already labeled for use in children. Also epoprostenol and prostanoids are approved in Europe and in the Netherlands, but not specifically for children. Of course we use them extensively in children, but they are not formally approved. I think in the Netherlands we are in a very privileged position that we have access to all available drugs and again they might not be approved for children, but if we have good reasons to provide them the children, we discuss with the insurance companies and they agree to reimburse it.

So I think in the Netherlands we have no restrictions to the available medications, so we can do what we think is the best for the child. That’s of course in contrast with different countries in Europe and they all have their own, well, regulations and reimbursement rules.  So already in countries directly neighboring the Netherlands, for instance in Germany, they don’t have access to epoprostenol, but they have iloprost, so it’s a good alternative, but it’s very strange that Germany is 50 kilometers from our center. They are dictated to use other medication than we have.

I think the importance of clinical trials is not the clinical trial itself, it’s, of course, the evidence for efficacy of medication. We give these medications to children because we think they work and because we are rather convinced now that there are no important safety issues, but I think the problem is we have not tested that adequately. That’s why we have the discussions with EMA, with the FDA, how to demonstrate efficacy because EMA and the FDA require of course efficacy to approve, but I think also as physicians, we should want to have this evidence because otherwise we put children at risk if we give them medication that doesn’t work. I think we have now 10 years’ experience of trying to do clinical trials in children with pulmonary arterial hypertension and we are not very successful.

We’re not very successful for several reasons. The problem is if we want to do efficacy studies, you have to know how to measure efficacy. In adults there have been some outcome measures, six-minute walk test, which are difficult or not that feasible in children, especially not in young children. So we are already looking for some time for good clinical outcome parameters for children with pulmonary hypertension. That’s difficult to validate. That’s one point. There are not good outcome parameters.

The second point is that although we don’t have trials, it is a very devastating disease and you cannot tell parents, “OK, we have no trials. We think it’ll worked, but we are not sure, so we first have to do a trial.” As physicians, we treat the children. So that means that, when the first medication came, all parents and doctors were very motivated to participate in the trial because then you got the medication.

Now the medication is available and both doctors and children are less motivated in participating in trials because they just want to have the medication.

The third point is that because it’s now almost standard of care, these medications, so it’s not ethical to do placebo-controlled trials anymore. So there are a lot of difficulties in which we struggle finding how to get to evidence that the medication is effective and which children are best treated with which medications. But I think a very good point in that is that now, in last years, everybody is convinced, both the physicians, the parents, the pharmaceutical industry, but also the regulators, or EMA and FDA, that we have to find different solutions, and already last year we have had very good constructive meetings to try to solve this problems, and I think we are moving forward in the field.

My vision for the future is that we further discover the mechanisms that play a role in in this disease. I think in the last years, we are also in this rare field of pediatric pulmonary hypertension where, until now, we were all dependent on expert opinion and personal experiences. We are now really getting data. International global collaboration has improved or increased enormously in the last 10 years and we now really are collecting data in which we can come with some evidence on treatment, on clinical course, on effects or adverse effects. So I think we are improving enormously, and that also, as I call it, pediatric pulmonary hypertension is growing up.

If you compare it to 20, 30 years ago, pulmonary hypertension was a rare disease and no one understood it and the message was, “if you have this disease, enjoy the time you have and we can only support you, but we cannot help you.” Doctors were not that into this disease because there was nothing to do. Awareness has grown enormously, the number of researchers involved has grown enormously, the number of physicians who are experts in it has grown enormously, and I think this is really an achievement of the last 20 years and I think it will bring a cure for this disease.

My name is Dr. Rolf Berger and I’m aware that I’m rare.

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