Good examples

We need more scientific studies that include children

Jenny Kindblom, läkare

Children and adults digest and react to medicines in different ways. Despite there being differences, many medicines have not been studied in children, and knowledge about long-term effects and side effects is poor.

– We need a greater focus on the child perspective, and increased investment in more clinical trials in children, says Jenny Kindblom, researcher and specialist in clinical pharmacology at Queen Silvia’s Hospital for Children in Gothenburg.

Jenny Kindblom opens the door to her office at the Sahlgrenska University Hospital. She has medical responsibility for the Pediatric Clinical Research Centre (PCRC), a unique trials unit for children and adolescents.

– I have a job that allows me to carry out research 50 per cent of my time, and during the other 50 per cent I have medical responsibility and am the study physician at PCRC. This means that I see patients who are taking part in ongoing studies conducted at the centre.

The centre was established two years ago at the initiative of Gothia Forum in collaboration with Queen Silvia’s Hospital for Children, and is one of few clinical trial centres in Sweden focusing on research and development of new treatments for children and adolescents. The aim is to create prerequisites for conducting more studies and trials in an optimal way, and to guarantee safety and minimise risks.

Through the collaboration with Gothia Forum, there are also a number of peripheral resources, such as lawyers and project leaders who can support studies initiated by either academic researchers, healthcare or industry.

– There are large knowledge gaps when it comes to children and medicines, and therefore a great need to conduct academically initiated studies to fulfil the knowledge needs that pharmaceutical companies, with their commercial drivers, are not very interested in.”

Medicines and children

Since 2007, there has been mandatory EU legislation governing paediatric medicine, the Paediatric Regulation. This requires each new medicine to be tested on children in well-controlled clinical trials. Despite the Regulation, knowledge about effects and safety of medicines in the child population is still limited.

– More research is needed, of good design and adapted to the child and adolescent perspective, says Jenny Kindblom.

When she started her medical training, she knew that she wanted to work with children, and and at first intended to become a paediatrician. But during training, she became fascinated by physiology and endocrinology, and was tempted to do research.

– Once I had completed my basic training, I wrote an experimental dissertation on molecular physiology. I am fascinated by how things work, and realised at an early stage that research was very exciting. I did my general internship in research at Sahlgrenska, and then continued training as a specialist within clinical pharmacology.

During this period, Jenny realised more knowledge and competence was needed within the area of children and medicines. As there were no suitable courses in Sweden, she applied to do a European course in Paris. Together with colleagues from all over Europe, she learnt more about regulatory issues and requirements, and how best to provide for the needs of families and children in conjunction with clinical trials.

– I learnt a lot, and it was a good basis for what I have been working with since then. I am also a representative on the Västra Götaland Region’s expert committee for children and medicines, which works to include the child perspective in all new treatment guidelines. At the end of my specialist training, I also spent a short period at the Swedish Medical Products Agency, and set up a good network there.

Children are discriminated against

When Jenny Kindblom had completed her specialist medical training, she was appointed to be part of the team writing therapy recommendations for children in a project organised by the Medical Products Agency within the national medicine strategy.

Many of the medicines used have not been studied in children, and it is common for medicines to be used off-label, which means outside formally approved indications, dosages, administration methods or age intervals, or on licence, which means medicines that have not been approved for the Swedish market.

Children with sleep disruptions are one example. The Swedish medicine directory FASS states that the preparation Theralen has the indication for sleep disruption in children from the age of two. But this is an old and difficult-to-dose medicine and may entail a risk for serious side effects, such as breathing disruption, which means that it is contraindicated for children under the age of two.

– In the new therapy recommendations, we recommended melatonin instead, which is a hormone that is well-tolerated as a medicine, but which lacks documentation to give it an indication for children. This is one of many examples of why there is a need for more scientific studies that include children, says Jenny Kindblom.

At PCRC, a study is in progress on obesity and includes children and adolescents between the ages of 12 and 18.

– When it comes to children and adolescents, you also need to involve the family and have access to several different tools to use in combination, and medicine therapy may be one of these tools. The hope is that we will find effective, functioning therapy strategies for children and adolescents suffering from obesity.

Ethically defensible?

Sometimes Jenny Kindblom gets asked whether it is really ethically defensible to conduct studies in children. But, she says, you can also turn the question around.

– Is it ethically defensible not to conduct studies in children? Thanks to research, we have made several major scientific advances in the last few decades, but many of these advances have not benefitted children.

If Jenny Kindblom had the chance to make important decisions that further improved the prerequisites for conducting clinical trials that include children and adolescents, she would invest resources in creating a model that made it easier to conduct research.

– Funding is normally a dilemma and a challenge for many academic researchers. I wish that there were opportunities to better support studies and trials initiated by the healthcare services, and that this was not associated with such high costs. I would also want to coordinate and simplify the application processes, and to create some kind of “hotel” for clinical trials, where academic researchers could book premises and writing desks easily in conjunction with studies.

There are also ethical and practical challenges when it comes to developing medicines that are designed specifically for children, in particular those children who cannot themselves decide on their participation in studies. For this reason, the ethical requirements for clinical trials are set extra high.

– It also generally takes more time when children are to be included in a study, and the funding bodies do not always take this into account. You cannot force or convince a child to take part in a study; it requires trust, security and confidence, which take time to develop.

There are also differences to consider when it comes to children and adolescents. During the emancipation years of adolescence, it can be difficult to convince a young person to follow study protocols and to do as their parents or the study leader says.

– This requires perceptiveness, and also pedagogic and psychological knowledge and sensitivity. I meet so many fantastic children and adolescents who are taking part in our studies, and who I get to know. It is very educational and exciting, and a strong driver for me. I think that children are the most important persons in the world.