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German Paediatric Research Network (PAED-Net)
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2009 Adis Data Information BV. All rights reserved. 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
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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
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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. Unauthorised copying
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),
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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. This material is
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-
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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
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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-
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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]. the copyright of the
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]
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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.
2009 Adis Data Information BV. All rights reserved.
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