Pediatr drugs 2009; 11 (1): 11-13

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German Paediatric Research
Network (PAED-Net)
Monika Seibert-Grafe,1 Raunhild Butzer2 and Fred Zepp3 1 Interdisciplinary Centre for Clinical Trials (IZKS), University Medical Centre Mainz, Mainz, Germany2 Coordinating Office of the German Paediatric Research Network (PAED-Net), University Medical Centre Mainz, 3 Department of Paediatrics, University Medical Centre Mainz, Mainz, Germany This material is
Clinical trials in children are mandatory to generate data on new drugs as well as on drugs used off-label or for unlicensed indications. The EU Paediatric Regulation introduced in 2007 provides the background, goals, andrequirements for pediatric clinical trials. The German Paediatric Network (PAED-Net) was established in 2002with a public grant from the German Ministry of Education and Research with the aim of developingcompetence, infrastructure, networking, and education for pediatric clinical trials. The network, consisting of six the copyright of the
pediatric clinical units and a coordinating office, has progressed very well and has achieved valuable improve-ments concerning the conduct of pediatric clinical trials. In addition, training programs have encouragedknowledge about clinical trials in investigators and nurses and have made medical professionals as well as thepublic aware of the need and advantages of trials in children. Although these trials are still challenging from the original publisher.
ethical, scientific, and clinical points of view, quality-controlled data are the prerequisite for sharing therapeuticinnovations for children and for applying the principles of evidence-based medicine to the youngest patientpopulation.
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Approach to Improve Conduct of Clinical Trials The difficulties in conducting pediatric trials and the complexi- To improve drug therapy in children and adolescents, clinical ty of their methodological procedures as well as the lack of and distribution
trials are mandatory to generate data on the safety and efficacy of knowledge on conducting pediatric trials and resources led to the drugs. The Regulation (EC) No 1901/2006 of the European Parlia- decision to create and fund a German Paediatric Research Net- ment and of the Council on Medicinal Products for Paediatric Use work (PAED-Net),[3] which started in 2002. In response to a call that came into force in all EU member states in January 2007[1] from the German Ministry of Education and Research (BMBF), is prohibited.
describes, in a clear and detailed way, the necessity for clinical six university medical centers out of 36 were selected for funding, trials of drugs under development, for drugs for which changes in based on a competitive application process, by an independent dosage forms or new indications are submitted for approval, and expert board: Cologne, Freiburg, Heidelberg, Leipzig, Mainz, and for off-patent drugs that are unlicensed or used off-label in pediat- Muenster with a coordinating office in Mainz. Overall, BMBF funding for the network was €5.4 million for 6 years plus funding In order to realize these trials in Europe, networking is needed.
for a trial in neonatology investigating the reduction of analgesic Therefore, a European Paediatric Network was considered a pre- and sedative agents in ventilated neonates by continuous infusion requisite for the achievement of the goals of the paediatric regula- of clonidine.[4] All six pediatric trial units are integrated in the tion. The European Paediatric Network will consist of national previously established Coordination Centres for Clinical Trials networks either already existing or planned in the EU member (KKS)[5] and are in close collaboration with the respective pediat- states (The Network of Paediatric Networks at the EMEA, Imple- ric university hospital. The advantage of being linked to the KKS as well as to the pediatric university hospital is the direct access to Fig. 1. Organizational structure of the German Paediatric Research Network (PAED-Net). The structure is identical at all involved universities but the
coordinating office is only located in Mainz. IT = information technology; KKS = Coordination Centres for Clinical Trials; lab = laboratory.
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all pediatric subdisciplines and their patients, and the support from Most of the on-going or 155 completed trials since 2002 are the KKS (quality management, logistics, biometrics, data manage- industry driven and about one-third are investigator initiated. The ment, monitoring, regulatory, and pharmacovigilance) [figure 1].
majority (80%) address drugs in the following areas: gastroenter-ology, neonatology, allergology, metabolic diseases, cardiology, The objectives of the PAED-Net are to develop expertise in nephrology, diabetes mellitus, pulmonology, dermatology, neuro- the copyright of the
multicenter clinical drug trials in the pediatric population and to logy, infectious diseases, oncology, psychiatric disorders, and build a network with a trial infrastructure that can act as a platform for multicenter clinical trials. The Paediatric Trial Units at the The clonidine intensive care trial (see Approach to Improve Universities of Marburg, Tuebingen, and Innsbruck, in addition to Conduct of Clinical Trials), the so-called network trial, resulted in original publisher.
the above-mentioned six university medical centers, became asso- considerable recruitment difficulties at those trial sites where the ciated partners of the German PAED-Net. Each Paediatric Trial established care differed from that required by the study protocol; Unit is staffed with a pediatrician and a study nurse who are this contributed to the delay in the enrolment of study participants.
responsible for trial conduct at the clinical site and investigator This trial also showed that more resources, training, and communi- recruitment. The network is coordinated by two medical doctors Unauthorised copying
cation than planned are often needed to conduct trials successfully.
working in the Coordinating Office who are responsible for or- In addition, the contract negotiations are complex, the detection ganizing and performing certified training programs and network and definition of serious adverse event/suspected unexpected seri- meetings, feasibility assessments, communication with industry, ous adverse reaction in patients with life-threatening diseases with ethic committees, and authorities, and reports to the funding body and distribution
co-morbidities and co-medication is difficult, and pharma- covigilance procedures have to be supplied to trial sites. Clinicaltrial conduct and data documentation need highly experienced and dedicated staff who feel responsible for the trial, and a lot of time is prohibited.
An intensive collaboration with other university hospitals, non- In order to train investigators and nurses appropriately in the academic hospitals, and private physicians has been established. In principles of clinical trials, a 2-day Good Clinical Practice (GCP) particular, this collaboration aims to ensure patient recruitment in pediatric trial course is performed twice a year and covers the following topics: drug therapy in children; off-label use; need for Harmonized standard operating procedures, a trial database (for pediatric trials; preclinical and clinical drug development in indus- network partners), standardized essential study documents (e.g.
try; principles of pediatric trials (e.g. ethical standards, determina- patient and parent information, informed consent, documents for tion of pediatric trial population, inclusion and exclusion criteria, assent), and a curriculum for training courses for pediatric investi- methods, trial medication, patients’ assurance); clinical investiga- gators, study nurses, monitors, and scientists in close collaboration tions of medicinal products in the pediatric population (ICH E11); with KKS have been established in addition to various and mani- Paediatric Regulation; Paediatric Investigational Plans; ethical and fold public works, (such as presentations, talks, articles, and regulatory requirements; application for trial approval; writing a study protocol; study design and biostatistics; informed consent/  2009 Adis Data Information BV. All rights reserved.
German Paediatric Research Network (PAED-Net) assent; clinical conduct according to GCP; responsibilities of Paediatric Regulation will result in better and more clinical pediat- clinical trial investigators; recruiting strategies; data documenta- ric trials that will generate data needed to improve drug therapy in tion; monitoring; audits; pharmacovigilance; study reporting; and children. Networking is mandatory to build up the necessary competencies, to facilitate co-operation, and to avoid duplicationof studies.
To meet industry interests and requests, PAED-Net members regularly advise companies with respect to planning and conductof pediatric trials. The most frequent topics on which advice is given concern epidemiology and therapy of the disease for whichthe drug is planned to be developed; standard therapy; the popula- No sources of funding were used to assist in the preparation of this article.
tion at risk; concomitant diseases; affected age groups; ethical The authors have no conflicts of interest that are directly relevant to the aspects; minimal burden (as defined elsewhere[7]); minimal risk (as defined elsewhere[7]); pregnancy tests; sexual abstinence;blood volume (as described elsewhere[7]); venous punctures; num-ber of required visits; physical examinations; study design (end- This material is
points, noninvasive parameters); and feasibility (number of pa- 1. Regulation (EC) No 1901/2006 of the European Parliament and of the Council of tients, probability of realization of trial protocols).
12 December 2006 on medicinal products for paediatric use [online]. Availablefrom URL: http://ec.europa.eu/enterprise/pharmaceuticals/eudralex/vol-1/ For the past 6 years, the members of PAED-Net have had some reg_2006_1901/reg_2006_1901_en.pdf [Accessed 2008 Nov 17] valuable experiences in networking. It became obvious that 2. The Network of Paediatric Networks at the EMEA Implementing Strategy [online].
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networking requires – besides pediatric and trial excellence – team Available from URL: http://www.emea.europa.eu/pdfs/human/paediatrics/ spirit, team players, and shared goals as well as trust and confi- 3. PAED-Net: a German paediatric network [online]. Available from URL: http:// To be prepared for the future the German PAED-Net will be 4. ZKS K¨oln [online]. Available from URL: http://www.zks-koeln.de/pdfs/ original publisher.
integrated into the German Society for Paediatrics,[8] which repre- 01_studien/aktive_studien/i_clonidin.pdf [Accessed 2008 Nov 17] sents all pediatric subdisciplines. More specialized pediatric clin- 5. KKS Network: coordinating centres for clinical trials [online]. Available from URL: http://www.kks-netzwerk.de [Accessed 2008 Nov 17] ical trial units are necessary to extend trial infrastructure and trial 6. Data on file, PAED-Net internal database, 2008 competence in Germany in order to produce quality-controlled 7. Ethical considerations for clinical trials on medicinal products with the pediatric data from well designed and conducted clinical trials, which will Unauthorised copying
population [online]. Available from URL: http://ec.europa.eu/enterprise/phar- eventually lead to the ultimate goal of better medicines for chil- maceuticals/eudralex/vol-10/ethical_considerations.pdf [Accessed 2008 Nov17] 8. German Association for Medicine in Children and Adolescents [online]. Available from URL: http://www.dgkj.de [Accessed 2009 Nov 19] and distribution
Correspondence: Dr Monika Seibert-Grafe, Interdisciplinary Centre for Clin-ical Trials (IZKS), University Medical Centre Mainz, Langenbeckstraβe 2, Pediatric clinical trials are challenging and demanding but necessary and worthwhile for progress in children’s care. The EU is prohibited.
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Source: http://www.izks-mainz.de/files/seibert-grafe_et_al_2009.pdf