Research group - Anders Rane

Almost thirty percent of the world's population are children. Despite this, there is a great shortage of safe and well-documented medicines for children. Conect4Children is an EU-funded pan-European cooperation project in which Sweden participates. The aim is to give children of all ages access to the same range of safe and effective medicines that adults have.

There is a worldwide dearth of medicines that have been scientifically documented in children of any age. Development of drugs for children is of great importance for medical and ethical reasons. This requires scientific and clinical excellence, educational efforts and competent clinical platforms collaborating in networks to collect pediatric patients in numbers large enough to conduct conclusive studies. Establishment of networks for this mission has been politically promoted in the European Union and United States.

Background

Less than one third of marketed drugs worldwide have any approved therapeutic indication for children of various ages, and less than half of them have ever been scientifically tested in children – for newborns less than ten percent. Children have the same rights as adults to be treated with effective and safe medicines and take part of new therapeutic treatment strategies. American (FDAMA 1997, Pediatric Rule 1998, Best Pharmaceuticals for Children Act 2002) and European legislation (Pediatric Regulation No 1901/2006) have now implemented legal claims to document pediatric effects, side effects and safety of any new drugs or new indications seeking marketing authorization.

The “Conect4Children” initiative (www.conect4children.org, COllaborative Network for European Clinical Trials for Children - “c4c”) is a large collaborative pediatric network that will facilitate the development of new drugs and other therapies for the entire pediatric population in Europe. The Conect4Children consortium aims to enhance the competitiveness of Europe as a critical region for developing medicines for children by using existing expertise, patient access and developing common processes to be applied to disease natural history studies, registries, studies of new therapies and comparisons of existing therapies.

The consortium is a novel collaboration between academic and private sectors that includes 33 academic and 10 industry partners from 19 European countries, more than 50 third parties and around 500 affiliated partners. The six-year multidisciplinary project started on May 1st 2018, and is probably the largest EU public-private-partnership consortium known. It is a pioneering opportunity to build capacity for the management of multinational pediatric clinical trials across Europe, bringing together key stakeholders across academia and industry. It will ensure that the voices of children, young people and their families are heard. Strong links with regulators have been established.

The medical and clinical pharmacological rationale:  The overall therapeutic result is dependent on the intrinsic features of the drug, its interactions with all biological processes that mediate effects and toxicity and that are part in any step of the uptake, distribution, metabolism, and excretion of the drug. There is a great variation in these processes among children, both within and between age groups, and more so than in adults. This is caused by the effects of the maturation itself on all these biological processes. The maturation itself may also affect with the expression of genetic traits that are important for pharmacodynamics and pharmacokinetics. This may be exemplified by polymorphic drug metabolic pathways where individuals with the “active” mode may appear as “inactive” early in life.

Aims

This project aims to generate a sustainable infrastructure that optimises the delivery of

clinical trials in children through:

  • a single national point of contact for all sponsors, sites and investigators
  • efficient implementation of trials adopting consistent approaches, aligned quality standards and coordination of sites at national and international level
  • collaboration with specialist and national networks
  • high quality input to study design and preparation through rigorous strategic and operational feasibility assessment
  • the promotion of innovative trial design and quantitative science methods
  • an education and training platform to shape the future leaders of pediatric drug development
  • the development of sustainable support for all these activities

One of the key goals of the project is to support the use of innovative trial designs to foster development of new drugs and their use in pediatric diseases and high medical need areas.

Importance

Clinical trials with medicinal products for pediatric use are one of the most sensitive areas in science – both from a medical and an ethical perspective. c4c addresses critical problems with the design, implementation and operational conduct of pediatric clinical trials, such as fragmented and redundant efforts between sponsors, sites and countries, the paucity of patients available for studies on many pediatric indications, and the need for multiple capable sites and expertise to make trials successful. The international and national networks will have a significant impact on how we develop much-needed innovative and improved medicines for babies, children and young people according to international scientific standards.

Research group leader Anders Rane

Anders Rane

Professor, senior
H5 Department of Laboratory Medicine

Group members

Estelle Naumburg

Affiliated to research
H5 Department of Laboratory Medicine

Monica Rydén Aulin

Affiliated to research
H5 Department of Laboratory Medicine

Jenny Kindblom

Assistant Professor in clinical pharmacology, Göteborg University

Other collaborators

A number of clinical PIs at various clinical sites (Third parties) in Sweden collaborate by recruiting and treating pediatric patients according to protocol. Prof Carlo Giaquinto (Padova) and Dr Mark Turner (Liverpool) are coordinators.

Research techniques

Feasibility, trial design, biostatistics, clinical methodologies for assessment of outcome parameters, regulatory affairs, pharmacovigilance.

External funding

Joint equal funding of about 140 Million € by the European Union´s Horizon 2020 research and innovation program and the Innovative Medicines Initiative 2 Joint Undertaking (IMI2 JU) under grant agreement n º 777389 Considered to be Europe’s biggest Public Private Partnership project.

Educational program

About ten digital/online courses in GCP, clinical drug development, and all relevant aspects of clinical trial research with tutorial dialogues and final examinations. In addition, a Master course (29 weeks) consisting of eight modules, each two weeks self learning + one interactive week with teacher. This course reaches the Bloom level 5. The Master course will be accredited. Estelle Naumburg and Anders Rane are members of the faculty for some courses and Anders Rane is also a member of the Educational Board.

Selected publications

Improved infrastructure and support needed for paediatric clinical trials in Sweden.
Mattsson H, Kindblom JM, Norman E, Rane A, Naumburg E
Acta Paediatr 2020 12;109(12):2740-2747

Tardy development of safe medicines for children: a Nordic network offers new platform to reduce this inequity.
Naumburg E, Rane A, Halvorsen T, Glosli H, Henriksen TB, Haraldsson À, Kallio J, Lepola P
Acta Paediatr 2019 06;108(6):992-993

Encouraging prospects for paediatric drug development in Europe.
Rane A
Acta Paediatr 2020 03;109(3):438-439

Individual variations in fentanyl pharmacokinetics and pharmacodynamics in preterm infants.
Norman E, Kindblom JM, Rane A, Berg AC, Schubert U, Hallberg B, Fellman V
Acta Paediatr 2019 08;108(8):1441-1446

Genetic Predisposition to Poor Opioid Response in Preterm Infants: Impact of KCNJ6 and COMT Polymorphisms on Pain Relief After Endotracheal Intubation.
Elens L, Norman E, Matic M, Rane A, Fellman V, van Schaik RH
Ther Drug Monit 2016 08;38(4):525-33