The need for information about new and existing drugs used in children was recognized in the European Union (EU) with the implementation of the Paediatric Regulation in 2007. In 2017, the 10-year review of the Paediatric Regulation identified barriers to the conduct of clinical trials, including delays in setting up and completing paediatric trials. Across Europe, the difficulties with clinical research are compounded by variation within countries and between countries. Ethics and regulatory review have national specificities. This paper describes the Collaborative Network for European Clinical Trials for Children (conect4children, c4c), which addresses selected difficulties in the design and conduct of paediatric clinical trials. c4c is a time-limited public–private consortium funded by the Innovative Medicines Initiative (IMI2). The elements of c4c are as follows: expert advice providing input on study design and/or paediatric development programmes (including patient involvement activities); a network of sites following harmonised procedures coordinated by National Hubs and a single point of contact for Europe; a facility for education and training for sites and trial teams; and support for managing data used by the network and a common paediatric data dictionary. c4c does not sponsor trials. c4c is taking a phased approach with careful piloting through industry and non-industry studies intended to demonstrate the viability of the network (proof-of-viability studies). c4c uses a co-design approach involving industry and academics within a clearly defined scope. A sustainable, successor organization open to all potential service users will be open for business before the end of IMI2 funding in 2024.

Paediatric drug development faces several barriers. These include fragmentation of stakeholders and inconsistent processes during the conduct of research. This review summarises recent efforts to overcome these barriers in Europe. Two exemplar initiatives are described. The European Paediatric Translational Research Infrastructure facilitates preclinical research and other work that underpins clinical trials. conect4children facilitates the design and implementation of clinical trials. Both these initiatives listen to the voices of children and their advocates. Coordination of research needs specific effort that supplements work on science, resources and the policy context.

Background There are no generally accepted age-appropriate reference ranges for laboratory values in neonates. This also matters for drug development. The International Neonatal Consortium (INC) is engaged to define actionable reference ranges of commonly used laboratory values in neonates. Methods A structured literature search was performed to identify standards or recommendations for publications that present neonatal laboratory data to assess the publication quality of laboratory values in neonates. Using a modified Delphi approach, an assessment and data extraction instrument to screen on completeness of information was developed. Results On 2908 hits, 281 papers were retained for full reading and 257 for data extraction. None of the papers reported a publication standard. Using the extraction instrument, most papers presented single country or unit findings. The median number of neonates was 120, with uncertainty on single or repeated measurements. Clinically meaningful information on age, sex, and medical conditions was commonly provided. Information on pharmacotherapy, equipment, analytical method, or laboratory location was rarely mentioned. Conclusions Published information on laboratory values for neonates is sparse, not systematic, and incomplete. This undermines efforts to compare treatments, safety monitoring, or clinical management. Furthermore, there appears to be no standard yet to report laboratory values in neonates. Impact There are no generally accepted age-appropriate reference ranges for laboratory values in neonates, leading to a significant knowledge gap, also for safety reporting and drug development in neonates. We performed a literature search to identify standards or recommendations for publications on neonatal laboratory data and to assess the publication quality of laboratory values in clinical studies involving neonates. Standards or recommendations for publications that present neonatal laboratory data were not identified, while published information on laboratory values for neonates is sparse, not systematic, and incomplete.

Regulation has strengthened the development of medicines for children in Europe through its system of obligations and rewards. However, opportunities remain to further optimize pediatric medicine developments, notably in relation to the implementation of the regulatory framework. This paper therefore describes bottlenecks identified by industry that occur during the medicinal development process, including those relating to the scientific advice process, pediatric investigation plan (PIP) development, compliance checks, and study submissions, and offers some considerations and insights to address these. Considerations, which are workable within the current legislative framework, focus on an integrated scientific discussion, optimization of PIP procedures and compliance checks, and an alignment of study-reporting requirements.

Congenital anomalies of the systemic veins in adults are often discovered incidentally, because they are usually asymptomatic. They may cause diagnostic and therapeutic difficulties in cardiology, phlebology and surgery. These anomalies may increase the risk of thrombotic and thrombembolic events. Together with polysplenia and situs inversus they are phenotypical components of heterotaxia. They may have various clinical consequences and may occur spontaneously or may be familial.