Which groups of people are particularly vulnerable, Mr Wiesing?
Urban Wiesing: The question takes us directly to the heart of the problem: Are we talking about people that are much more likely to be treated unjustly, about higher damage potential from certain treatments, or is it more a question of being able to consent? By some attempted definitions the list of vulnerable groups risks becoming extremely long. In an exaggerated sense, we could say that only white, well-off, cis men in their prime should be excluded. Yet this does not get us any further. So we have to be more specific and ask what characterises certain groups and which different measures can protect them. For example, are pregnant people fundamentally vulnerable or only in a certain regard?
Mr Pfister, you treat children and adolescents with cancer. Are they all equally vulnerable?
Stefan Pfister: Here too, we have to differentiate. From the age of 12 and up, adolescents are considered partially capable of consent, patient information is already today adjusted to the age of children and is available for various age groups. The concept of vulnerability should provide protection in a positive sense. Should it, however, mean less or even no access to innovative treatments, it can also be a disadvantage. The concept of vulnerability then turns from a privilege into a problem, especially for children and adolescents with life-threatening or even fatal diseases.
While excellent studies now show that most medicines for children, calculated based on body surface size, is metabolised in the same way as in adults, we are still seeing long latency periods due to regulations aimed at actually protecting these groups when it comes to using medicine. Studies indicate around six years on average. This is absolutely unacceptable.
Wiesing: We already differentiate in terms of ability to consent. From a certain stage of development adolescents have a right to object to participation in research. Adolescents with chronic illnesses often understand their illness better than adults. If they can estimate the “scope and significance” of the research, they ought to give their “informed consent” to participating in a study.
The World Medical Association’s Declaration of Helsinki also refers to the risks and burdens related to participation in clinical studies. The aim of your working group is to specify what is actually meant by the stipulated “minimum risk” and “minimum burden” in a clinical study on vulnerable people. Are there already ideas for how to achieve this?
Pfister: We weigh up risks and benefits every day in our profession. In the declaration, however, the severity of the illness has to date not been considered at all. Differentiating between light illnesses and diseases that could lead to a child’s death if left untreated is extremely important in our view.
Wiesing: We make this differentiation in terms of treatments, so this should also be the case in research.
Pfister: Especially since almost all child oncology treatments take place as part of clinical studies. Today, 70 to 80 percent of children and adolescents with cancer are initially treated as part of studies. This means that a strict differentiation between therapy and research is not possible.
We have the impression that the “subsidiarity principle”, according to which children and adolescents are only able to access new treatments after trials on enough adults, is interpreted differently in different countries and even within the European Union (EU).
What about adults not capable of consent? They also count as a vulnerable group.
Wiesing: Yes, and that is why, following the principle of subsidiarity, research on new treatments should first take place on non-vulnerable people. But what does this actually mean? Practically, it can lead to delays in the availability of new treatments, so we should then think about how we can reduce this time period in a way that is ethically acceptable.
When it comes to adults not capable of consent, group benefits of research is excluded as a criterion for permissibility, for example in studies on people with dementia. This is not the case for adolescents. However it is possible that some of them, in their healthier days, would have liked to help other patients by participating in research.
Pfister: From paediatric research we know that 95 percent of families hope that the studies their child participates in also help other children, and this is very often the case when it is assumed that the currently affected child only has a small chance of benefiting from the study in question.
Wiesing: We feel it is important to really look at the practical effects of differing regulations. But we are still at the beginning of this discussion.
What are you expecting to take away from the international conference “Research with vulnerable people” in May?
Pfister: We would like to better understand how countries can differently interpret the universally applicable Declaration of Helsinki and the EU regulations, including the Clinical Trial Regulation and the Data Protection Ordinance. In paediatrics especially, we see again and again that studies considered unproblematic in countries such as France, Italy, the Netherlands, United Kingdom and Scandinavia, meet with much more difficulty in Germany and need more time to receive approval from the authorities. What adjustments can we make here? We need to look at how these regulations are interpreted and implemented.
Wiesing: With the conference we’re aiming to bring together the work of various stakeholders. We consider the Leopoldina’s task to be the development of recommendations based on good data and a differentiated perspective.
The Interview was conducted by Adelheid Müller-Lissner