Clinical trials are an essential part of advancing knowledge and improving healthcare worldwide. Advances in paediatric research across the globe to improve the lives of babies, children and young people have dramatically reduced rates in morbidity and mortality and increased the quality of life, for example, reducing sudden infant death, increasing the life expectancy for children with thalassemia, cystic fibrosis etc.

However, despite these advances, current data suggests that approximately 50% of children’s medicines used across Europe are not approved for children’s use and/or not available in a pharmaceutical form suitable for children (Toma M., 2021).  This means that many medicines have not yet been tested for efficacy and safety in clinical trials for children, a number which rises significantly in neonates (Conroy S. et al. 2000; Teigen A. et al. 2017; Pineiro Pérez R. et al. 2021), resulting in the risk of inefficacy, and/or adverse reactions in children. This data suggests the ongoing need for clinical trials within the paediatric population that can be conducted as both industry or non-industry (academic) trials.

Collaboration

Non-industry trial costs (regulatory, investigators, clinical operations, e-CRF, monitoring, statistics, etc) are covered through grants (governmental, national, EU, charities) whereas in industry trials these costs are paid directly by the company itself. Independent of funding mechanism, the optimal environment for clinical trials involves collaboration between both academia and industry, which is one of the driving forces behind the c4c project. When the financial and organisational strengths of industry are shared with academics, this enables better design, organisation and performance of studies for the benefit of scientific knowledge and healthcare. Industry can benefit from academics in the design of studies, the definition of endpoints, and the selection of centres to perform the research. Sharing the industry database with academics can lead to further exploration of additional questions and raise new hypotheses (Laterre P.F. and François B. 2015).

Both types of trial have the ultimate goal of striving to improve paediatric healthcare, by providing evidence of the efficacy and safety of a new product in children. The focal points of both do differ though: industry trials tend to focus on trials which will provide evidence to support use in children and licensing by a regulatory authority. Non-industry trials tend to focus on the unmet medical needs where the economic stimulus may be lower. Industry often is researching the efficacy of a new drug or product through clinical trials to support a licence whereas non-industry trials often seek to compare one intervention to another.

Proof of Viability Trials within c4c

As part of the development of the c4c network, several Proof of Viability studies (clinical trials) are currently either underway or imminently foreseen. 3 non-industry studies are currently running and 4 industry studies are due to open by the end of 2021. A brief overview of the non-industry studies is outlined below:

TREOCAPA
The TREOCAPA trial examines the prophylactic use of paracetamol to close a persistent ductus arteriosus (PDA). The ductus arteriosus is a blood vessel that allows the blood to skip the circulation into the lungs when a baby is in the womb. This blood vessel usually closes in babies shortly after birth but very often does not in extremely preterm born babies (23-28 weeks gestational age). A PDA can cause permanent lung damage as well as feeding and growth problems. This study is a Phase II/III randomised, double-blinded trial carried out in 65 neonatal intensive care units of 17 European countries. To date, 19 sites have been opened and 22 patients recruited. For more information please see: https://www.efcni.org/activities/treocapa/

cASPerCF

The cASPerCF trial aims to assess the dose of an antifungal drug called posaconazole in children and young people with Cystic Fibrosis who have Aspergillus infection. Aspergillus is a fungus commonly found in our environment. The tiny Aspergillus spores which are transported by air, can enter the lungs during breathing. Normally, this will not cause any problem, but in people with underlying lung disease, it can lead to infection. Children aged between 8 to 17 years old with Cystic Fibrosis across Europe will be recruited into the study. The first site for recruitment has just been opened. For updates and more information please see: https://twitter.com/caspercfstudy?lang=en

KD-CAAP

KD-CAAP is a multi-centre, randomised trial of corticosteroids plus standard of care treatment versus standard of care treatment alone to prevent heart complications in Kawasaki disease. Kawasaki disease is a disease where arteries, particularly the coronary arteries in the heart, become inflamed, sometimes causing irreversible heart damage, heart attacks or even death. This study will work out whether corticosteroids plus standard treatment is better than standard treatment alone to treat children and adolescents across Europe aged between 30 days and 15 years who have Kawasaki disease. The first patient has already been recruited into the study. For updates and more information please see: https://twitter.com/kdcaap?lang=en