A scientist behind a microscope, in a brightly lit lab, surrounded by petri dishes and test tubes in which all sorts of experiments are brewing. And then, suddenly, a leap of joy: yes, touchdown, finally, that rare form of cancer can be cured.
An exciting and romantic idea for a Netflix miniseries but, of course, reality is much more intricate. After all, does that miracle drug also work with mice and men, just like it did in that petri dish? And, more importantly, is it safe to use at all?
In real life, a long journey along testing stages will follow, and once a drug will finally have reached people, it will still only be in a small group, during a so-called ‘clinical trial’. A carefully selected number of patients will then receive the drug. Safety will be tested first, and then effectiveness. It will take years before a new drug is approved to treat all patients with it.
“And that makes sense: we need to be sure that a drug is safe, and that it has added value compared to other drugs. But, still, the whole process could really be accelerated quite a bit,” says Neeltje Steeghs, professor of UMC Utrecht’s new chair ‘Early clinical drug development in oncology’.
Neeltje will now fully focus on that acceleration from lab to patient. And not just within Utrecht, but nationwide. How will she do that concretely?
Neeltje focuses on early clinical studies: new, experimental treatments just coming out of the research lab and ready to be tested in humans.
Once the lab phase is over, researchers and physicians (the ‘clinicians’) must then join forces to select patients for the clinical trial. However, Neeltje finds that the research and clinical worlds regularly do not interconnect well enough, leaving a drug stuck between the lab and the clinic for too long.
“Researchers and doctors should talk to each other more and earlier on, long before a drug comes out of the lab. I will help them with this as a facilitator: I want to connect them at an earlier stage. And not only within one academic hospital, but also other academic centers, hospitals, pharmacists and other companies need to be hooked up earlier.”
This is important not only to get new treatments ready sooner. “Researchers may be looking into something great for a tumor type for which three other good drugs already exist. That’s a shame. This can also be prevented if better and earlier communication is established between the different worlds,” says Neeltje.
Administration burden is also something that should be addressed to speed up clinical trials, Neeltje believes. “You have to deal with so many regulations these days, and different (ethics) committees that you have to go through. And there is a lot more paperwork than 20, 30 years ago, not only for doctors and researchers but also for nurses and patients. Everyone suffers from that increased administrative burden now, and we’ve all done that to ourselves as a society.”
Neeltje is involved in several (inter)national working groups to address this. “Here again, it’s simply a matter about talking to each other more. Which study are we going to choose? What kind of patients will participate in it? Which step can we omit to speed up the study? If you sit down with a group of people beforehand, there is a better chance that your drug will be developed faster in the right place.”
Once a clinical trial has been set up, it becomes important that as many patients as possible with that specific tumor type will have the opportunity to participate in it. This may be their last resort to live longer or with a better quality of life.
Neeltje often experiences this with her own patients. In addition to her professorship, she works as a medical oncologist, three days a week at the Antoni van Leeuwenhoek in Amsterdam. “From all over the country, people are referred to me. ‘Do you have another treatment for me?’ they then ask. You want to help your patients in every possible way. Then, of course, I start looking for hopeful clinical trials, not only at my own hospital, but also at other centers.”
And that is quite an intricate process, because there is not some sort of national database of ongoing early clinical trials in the Netherlands. “Too bad, because as a result, it still makes a huge difference at which hospital you start your treatment as a patient, and whether your specialists know the right people and pathways, and if they are familiar with the Dutch research structure. Even though, we are already really good in working together in the Netherlands, centers could share information about their studies in a better way. Sometimes, they can act like small islands. Hospitals then don’t know from each other which trials are running but individual doctors often don’t either.”
To solve this matter, Neeltje and her team are now working hard on a system that tracks all early clinical studies in the Netherlands. “We are now trying to map that of all academic centers: which trials are being done where, and what kind of patients are they looking for? For example, a patient in Groningen may be suitable for a study in Rotterdam: how will they find each other? Soon, there will be one system for all patients in the Netherlands.”
The first test version of the system will be ready by the end of this year and will only include early clinical trials for solid tumors. “A test version for all tumor types at once is not doable. But hematologists, neurologists and lung oncologists have already indicated they would like to participate, so that’s the next step we will take.”
The first version will not be tested nationwide but on a smaller scale, at the centers participating in Oncode Accelerator. Within this consortium, several public and private parties work closely together to get new cancer drugs to patients faster. Neeltje leads the National Platform for Early Clinical Studies within Oncode Accelerator.
“After the test phase with Oncode Accelator partners, we would also like to involve general hospitals, general practitioners and especially more patients. But we still have a long way to go. Because we will have to deal with patient privacy, and the fact that not every hospital works with the same administration system. And there is also competition involved: pharmacists who participate in studies do not want to give away too much to competitors. And who is going to maintain the system and keep it up and running? So, it will really be a process of negotiating and maneuvering: what are people willing to share with each other? But if we work closely together, and we can do that like no other in the Netherlands, we will get there.”
The current design of studies also often makes it difficult for physicians to find an appropriate, hopeful clinical trial for their patient. “I used to do clinical trials with all my patients with cancer, so with multiple tumor types. But nowadays, many drugs are tested very specifically, for one type of cancer. As a result, the likelihood that a medicine will work is a lot more logical than it used to be. Therefore, the study will get funded faster, proceed faster, and the drug will be registered sooner.”
The downside, however, is that the medicine will ultimately only be approved to use with a small, specific target group of patients whereas it might also be suitable for other tumor types. “This is really the biggest dilemma in my daily work with patients: then, I find a trial that would theoretically be suitable for them, but they are not admitted because they have a different type of cancer. Especially for people with a rare form of cancer, it is now hard to find a suitable trial because of this.”
Neeltje therefore would like to motivate researchers and doctors to set up their own studies in which they test already approved drugs in other sorts of cancer. “These are really so-called ‘low-hanging fruits’: studies that can be started relatively quickly, with a drug that can be approved quickly for other types of tumors. You will just have to get the pharmaceutical companies on board, because you need the drugs from them. And you will often have to put in money yourself as an institution. So, you will have to be prepared to do a lot of lobbying before your study will take off. In my new role, I want to make this easier for researchers and doctors. That way, all those relatively easy clinical studies will be set up and completed faster.”
Neeltje is not only advocating the faster introduction of new medicines. She also strives for better use of existing therapies. “I think that’s actually step one. Why does a medicine work with one person and less with another? That often is a result from not everyone absorbing the same amount of the drug in his/her blood. If you take a pill, your blood may contain ten times as much of the drug compared to someone else’s blood. And even within one person, the level may vary, depending on when you take a pill, what you eat and what other medications you take.”
Neeltje aims for doctors to personalize medicine dosages. “We do that very little in cancer treatments, while it is normal practice with, for example, antibiotics, HIV therapy and antidepressants. Then, doctors regularly check: how much do you have in your blood, should we add or subtract something more? With cancer, we invent expensive, new drugs instead. 30 percent of patients with cancer are underdosed, and 15 percent are overdosed: we should solve this first.”
And that’s fairly easy to do. “Doctors should take blood samples more often and think: how is my patient’s body handling this drug? I do that myself all the time, the clinical pharmacologist in me wants to figure it out. But doctors often don’t know well enough how a drug works. More attention should be paid to that within training.”
Even in the research phase, tailored dosing should already be a focus, Neeltje believes. “What is a ‘normal’ blood level with a certain drug? Include that in your research. Then, it will be easier for doctors to adjust the dosage. I find it shocking how long we have actually known that people with cancer are under-treated. I once promised myself: I want to have personalized dosages introduced for every patient in the Netherlands who can benefit from them. And then I’ll do so for the rest of the world, haha.”
How does the Netherlands actually fare internationally, in terms of experimental treatments? Because sometimes they tend to pop up: stories about people who received treatment abroad because they could not get it here.
“It’s a subject that is very much alive, but at the same time it’s also a grey area for many people. The general idea seems to be that in the Netherlands we are stricter in admitting new medicines, or, even worse, that we are lagging behind. But that is absolutely not the case,” says Neeltje.
“Within Europe, the Netherlands is one of the fastest countries to introduce new drugs. Almost everything that is approved in Europe is available in the Netherlands, as opposed to many other countries.”
Of course, there are examples of drugs that are not available here. “Before we introduce anything here, it first goes past a committee of medical oncologists. We then look at whether a new treatment will really have added value in the Netherlands. What is new is that we, as medical oncologists, sometimes approve a medicine whereas it does not receive reimbursement status from health insurers,” Neeltje explains.
“This is rare, but does occur nowadays. In such a case, we won’t treat patients with such a drug anyway in the Netherlands, even if a patient wants to pay a lot of money for it. That would not be fair: healthcare should be the same for everyone. But there are, of course, countries where you can then buy such a treatment.”
The research climate is also perceived as favorable in the Netherlands. Neeltje notices this, for example, when she meets foreign colleagues and companies at scientific congresses. Pharmacists are also positive. And that is important because they largely fund research.
“In the Netherlands, we like to think along but always remain critical. In clinical research, we are very meticulous, we have a good infrastructure, with quite a few people who are great at lobbying. Also, people here are more used to cooperating with each other compared to other countries. This is also necessary because we live in such a small country: we need each other,” Neeltje explains.
“In other countries, hospitals don’t know each other and each other’s patients at all. Another advantage: our patients do not have to travel so far. Unlike in Australia, for example, where people have to drive ten hours to reach a hospital.”
The Dutch collaborative mentality is all the more important in these turbulent times. Neeltje: “We have a very good structure in place. We work together with other hospitals, but also with, for example, pharmaceutical companies, technical universities, AI developers, et cetera. Furthermore, academic development will always be necessary, because there are always questions that pharmacists are not going to answer. Spinoffs (companies of researchers, which are closely linked to university hospitals – ed.) are also becoming increasingly important in this regard. With all the cuts to science by the current Dutch administration, and the political climate in the US, I really see gains in our talent for collaboration. By working together, with all the new research opportunities and options for patients, we are really going to succeed.”
More information about Oncode Accelerator
- Neeltje Steeghs (1977) grew up in Delft, and studied and obtained her PhD in Leiden.
- She started studying biomedical sciences, but switched to medicine after a year.
- Neeltje specialized as an internist/medical oncologist, and she is now also a clinical pharmacologist.
- She combines both positions three days a week at the Antonie van Leeuwenhoek/Netherlands Cancer Institute (AVL-NKI) in Amsterdam.
- Two days a week, Neeltje is professor of ‘Early clinical drug development in oncology’ at UMC Utrecht.
In addition, she coordinates the National Platform for Early Clinical Research at Oncode Accelerator.
- With her husband Ton, Neeltje runs a family with four (foster)children from 17 to 22 years old, a cat and an aquarium filled with guppies, in Leiderdorp.
“It seems like a lot, but all the pieces of the puzzle are now coming together at the right time. I love researching and finding the pieces of the puzzle, and that’s why I get such energy from my work. My husband and children see that too. There is still enough to research and figure out, and in 40 years’ time there will still be, because it is an illusion to think that we can quickly prevent or cure cancer 100 percent. Of course, I hope we will, but then there will still be other puzzles to solve.”