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There is only one way forward to personalised care

The narrow corridor in the UMC impresses with its nameplates, all professors. His room is functional, study books on the shelf, sober. The average accountant has a similar room.

"How do I get the greatest impact for the patient?", Timothy Radstake asks himself. He wants to work in a meaningful way, to have an impact. That is possible in the United States, where the budgets are higher. It is real passion that brings him as senior medical director early clinical development at AbbVie to Chicago. Radstake is not sensitive to status, I notice. Because he already knows: the Chicago office has similar rooms.

Timothy Radstake is a rheumatologist and professor of translational immunology at UMC Utrecht. In Utrecht, Radstake is the leader of the largest research group within the immunology lab, where several specialisms have been combined entirely in line with the ideas of Personalised Healthcare. "It's strange that we classify patients according to their diagnosis and start treating them with drugs in that way." Timothy Radstake is a great advocate of systems medicine: the determination of a molecular profile of each patient, which shows where something is wrong. This opens up the possibility of intervening before someone develops a disease. "There is only one way forward on the road to personalised care. The only way is to look at patients molecularly and not in terms of the different diseases. We need to arrive at a different criterion."

 

His future dream is to create unique cohorts to make the molecular network lead the way in diseases. "I want to fight negativism, doubt and ignorance about systems medicine.

It is a unique opportunity that I get. A job has been created on the whole of immunology, so I can apply all my insights and personal knowledge... And I will be head of transactional medicine Immunology and that is, of course, where my heart lies. To research how you can predict how patients will react. There are many opportunities for me to apply molecular profiles in trials. If I can implement just 50% of my ideas... then we'll be making great strides. Suppose we could make a basket trial for several diseases... yes, that would be nice... we also need EMA and FDA for that. The 'regulators' still prescribe that you have to do a trial with one diagnosis and xx endpoints. Whereas we want: you take 20% of the patients with five diagnoses and then your molecular change is the endpoint. We are therefore in a difficult transition phase; it is a major change for medicine. You can already see this in cancer: Pembroluzimab, for example, is registered for cancer with certain molecular changes 'no matter what' as long as you have this specific molecular change. You would want that for our diseases as well."

In Utrecht, Timothy Radstake worked on a cohort of 25,000 patients, with more than 20 infectious and immunological diseases. Soon, in the United States, everything will be bigger: the cohorts to work with, the budgets, the responsibility. He does not like people who come with predictable reproaches of 'you are going to the dark side', from a university medical centre to industry. "Bottom line, companies want what we want. Then people say: but pharma companies want to sell drugs! That's right. That side of the coin overshadows the other side: really understanding the origins of diseases and preventing them. Pharma employs many motivated people who want to generate impact. And often 30 to 40% of the turnover goes back to R&D. To realise what we want, tens of millions of euros in budget are needed."

Getting a foothold in systems medicine is not easy. "Many research proposals that I made with the term systems medicine in the title/description were not accepted. The large subsidy providers suggest that they want so-called high-risk, high-gain research. I see too little of this in the accepted research proposals. Unfortunately, acceptance by the government is also extremely slow," says Radstake. "We do have projects that Health Holland (Top Sector Life Sciences & Health) co-finances, and then you can add 20 to 30 per cent to the budget. That is a good programme. So many proposals are submitted to the National Science Agenda that you can't see the wood for the trees. The question is whether it is at all possible and cost-effective to have everything reviewed. There are either too many researchers in the Netherlands or too little budget. I leave it to others to judge this.

"I have been a professor here for 7.5 years now and it breathes systems medicine, it will stay that way," he said. "I live in the Netherlands and also want to continue to supervise the PhD students I have. There are four employees in the senior leadership of the group and they will continue my work. The Netherlands has a good infrastructure for doing trials. It would be great if our country could become an important hub for systems medicine. If I can contribute to that from the United States, I am very happy to play that role. The PHC Catalyst Alliance brings together interesting people who together can make an enormous contribution to awareness. It is impressive what has been achieved in such a short time. From my other perspective, I would like to continue to be involved in that."

Working internationally is not necessarily more effective

The idea that you do better studies by bringing together all kinds of international data is not necessarily effective, says Radstake. "If the genetics of the people in the cohorts are different, it is sometimes difficult to make a single molecular model. We have a trial with two cohorts from the Netherlands and two cohorts from Italy, and the results are really different. But then the fact that we can get many patients together 'in a small clump' and that labs are close by is the enormous added value we have in the Netherlands." Large European grants require researchers from different countries to work together. Radstake thinks that this does not always benefit the research itself. Working with different labs increases uncertainty, while this is not always necessary.