Table 4 Answers from four professionals to the interview questions

Why did you choose the theme 'Disease mechanisms and models' as most important?

All the themes listed are extremely important in the research field. With my answer I intended to highlight how central the role of disease mechanism comprehension should be in the road to therapy development, preventive strategies, healthcare and disease diagnosis. In other words, I believe that all the others are not truly possible without this nuclear field.

I mentioned this point as it is a sub heading of origins of disease in my mind. But often 'origins of disease' is mainly genetic diagnosis or genetic research, as we more and more see that genetic tests give an answer in only a small proportion of dystonias. Therefore it is important to tackle the underlying mechanisms of the disease in terms of networks and models of these networks. This may open new insight into the origin of disease and new therapeutic models.

I consider the lack of good disease models that validly represent the disease in humans and the lack of mechanistic understanding to be the biggest bottleneck on the way to a causal therapy. Developing therapies for me is inherently linked to this. Everything else is secondary for me because it is not causal or 'disease-modifying'.

Based on these research findings, we can develop new treatments. It allows us to see the disease in a broader perspective. We first need to understand the mechanism and then think about how to treat the disease.

Can you imagine that patients think it is most important to do research on 'Developing therapies and preventive strategies'?

Yes. Patients are very disabled by the disease, socially and physically. This is both a burden and a stigma. We try our best to help them, but the results may not be good enough for them to go back to a normal life. Therefore they hope to get a better cure and preventive treatments to get back to normal or the best condition possible.

This is a huge topic, particularly from the patients' point of view. But also from ours: this is the final goal shared between all of us. Research on this topic is very important, but unfortunately not possible yet for all diseases. We still miss important information about disease mechanisms. This is the crucial point. However, studying disease mechanisms (and models) is the first step for developing therapies.

I can very well imagine that this is the most important issue for patients. We need causally effective "disease-modifying therapies". Patients see it as hope from the end, I as a scientist from the necessary beginning and stony path (disease models and mechanism).

Yes. Patients want to have a treatment in their lifetime.

What needs to be done so that clinicians and patients understand each other's needs in which research theme needs to have priority?

We already communicate on a regular basis with patient's associations. If we want to broaden our view, we could:

• Increase the amount of webinars and (when possible) meetings with patient's associations.

• Ask patients to complete a survey about research. How do they see and understand it; what are the different sources where they can find it; to what degree do they understand the objective, results and relevance of research; do they understand the differences between clinical/therapeutic and pathophysiology?

• Propose research objectives or projects on the websites of patient organisations. This will Increase their awareness and understanding. It may motivate them to be involved in research (which is currently not at its optimal rate).

• Make the results of this survey available on the website of ERN-RND.

• Organize an (online) discussion on this topic.

I had really good experiences regarding 'mixed' meetings: with scientists and families. I found the families' part of these meetings very interactive and useful for both sides. Sometimes researchers need to remind themselves what the disease burden is for patients and families.

It is crucial that patients understand that the development of a drug requires understanding of mechanisms, and the transfer tot the clinic the necessary intermediate step of testing in good models—both of which require patience. I believe that every doctor-patient contact should contribute to this exchange of knowledge. Institutionally, I see the opportunity for strong involvement of patient organizations in scientific congresses and on the other hand the invitation of professionals to events of the patient organizations.

There needs to be collaboration between patients and researchers. In my experience there is no need to convince patients about the need for research on disease mechanisms. They do have a different perspective. But for example in research studies, patients ask 'will this help me?', and when we explain that unfortunately it will not, but it may help the next generation of patients, they think this is a good reason to participate.