ABSTRACT
Title
Clinical Reserach In Paediatrics: New Momentum And Critical Aspects
Authors
C.A. Rizzi, C. Conz, C. Fiorella
Medical Department, Medineos s.r.l., Milan, Italy
Abstract
Introduction - Clinical Research in Paediatrics represents one of the major focus of Regulatory Bodies. As the number of medications approved for paediatric use is relatively scarce compared to the off label use, a recent Regulation (No. 1901/2006) states that the applications for new chemical entities/formulations has to be accompanied by specific Paediatric Investigational Plans (PIPs) agreed and approved by EMA since the early stages of development. This presentation is aimed at providing a first evaluation of paediatric research 4 years after the Regulation came into force (2007).
Methods- First evaluations have been made on the EMA website database, in order to identify the major fields of off label use in Paediatrics. Then, these data has been matched against the therapeutic fields of approved PIPs. Since the scientific interest of the medical community is underlying the dissemination of results via publications, an indirect index of the efforts of Paediatricians has been searched in scientific papers quoted in PubMed.
Results - A number of 399 approved PIPs (either original or modified) are currently listed in the EMA database. For comparison, only 14 of the submitted PIP (3%) have been rejected, thus demonstrating that there is a good co-operation between sponsors and regulatory authorities in agreeing plans of development in Paediatrics. An additional number of 170 projects have been agreed by the submitter and EMA to be categorized as waivers, i.e. not suitable for use in children.
The highest number of PIPs by therapeutic fields are endocrinology, oncology, cardiovascular medicine, infectious diseases. This ranking is significantly different from that of the off-label use of drugs in children as results from an EMA survey: antiarrythmics, antihypertensive, proton inhibitors and histamine-antagonists, antiasmathics. Another controversial aspects consists in the focus of resarchers in Paediatrics as it may be inferred by the publications, which mainly reflect non-registration investigators-initiated trials (in Italy: no-profit studies). In 2010, 373 original papers have been published (reviews are excluded). The ranking of therapeutic areas is rheumatology/immunology; pain; respiratory diseases; anaesthesiology. Such list is significantly different from the two reported above of off-label medications and PIPs. In addition, a high percentage of published studies, accounting for 44% of the total, are in the field of neonatology, which is often matter of concern by the Authorities for the limited number of PIPs which include trials in the newborn.
Discussion and Conclusions - This research on multiple databases shows that in spite of a general increase of interest in clinical research in Paediatrics, there are still discrepancies and different point of view by the major stakeholders. The main focus of the Authorities is to make available the higher number of medications with specific authorization for use in children, thus overcoming the predominant existence of not appropriate, not evidence-based prescriptions off label. On the other hand, PIPs reflect the pipelines of Industries, which are obliged – because of the Regulation 1901/2006 – to adapt their portfolio to an additional use in children. The comparison between the medical need expressed by these two stakeholders is evident. Finally, Investigators show their scientific interest on therapeutic areas which match neither with the off label list of medications nor with the distribution of PIPs.
It is concluded that more intense interactions are needed by the three major stakeholders (Authorities, Industry and Investigators) in order to align on a common goal for clinical research in children.
References
Report on the survey of all paediatric uses of medicinal products in Europe. www/emea/europa.eu
Opinion and decisions on Paediatric Investigation Plans (PIPs). www/emea/europa.eu
PubMed Central homepage. www.ncbi.nlm.nih.gov/pmc/
Methods- First evaluations have been made on the EMA website database, in order to identify the major fields of off label use in Paediatrics. Then, these data has been matched against the therapeutic fields of approved PIPs. Since the scientific interest of the medical community is underlying the dissemination of results via publications, an indirect index of the efforts of Paediatricians has been searched in scientific papers quoted in PubMed.
Results - A number of 399 approved PIPs (either original or modified) are currently listed in the EMA database. For comparison, only 14 of the submitted PIP (3%) have been rejected, thus demonstrating that there is a good co-operation between sponsors and regulatory authorities in agreeing plans of development in Paediatrics. An additional number of 170 projects have been agreed by the submitter and EMA to be categorized as waivers, i.e. not suitable for use in children.
The highest number of PIPs by therapeutic fields are endocrinology, oncology, cardiovascular medicine, infectious diseases. This ranking is significantly different from that of the off-label use of drugs in children as results from an EMA survey: antiarrythmics, antihypertensive, proton inhibitors and histamine-antagonists, antiasmathics. Another controversial aspects consists in the focus of resarchers in Paediatrics as it may be inferred by the publications, which mainly reflect non-registration investigators-initiated trials (in Italy: no-profit studies). In 2010, 373 original papers have been published (reviews are excluded). The ranking of therapeutic areas is rheumatology/immunology; pain; respiratory diseases; anaesthesiology. Such list is significantly different from the two reported above of off-label medications and PIPs. In addition, a high percentage of published studies, accounting for 44% of the total, are in the field of neonatology, which is often matter of concern by the Authorities for the limited number of PIPs which include trials in the newborn.
Discussion and Conclusions - This research on multiple databases shows that in spite of a general increase of interest in clinical research in Paediatrics, there are still discrepancies and different point of view by the major stakeholders. The main focus of the Authorities is to make available the higher number of medications with specific authorization for use in children, thus overcoming the predominant existence of not appropriate, not evidence-based prescriptions off label. On the other hand, PIPs reflect the pipelines of Industries, which are obliged – because of the Regulation 1901/2006 – to adapt their portfolio to an additional use in children. The comparison between the medical need expressed by these two stakeholders is evident. Finally, Investigators show their scientific interest on therapeutic areas which match neither with the off label list of medications nor with the distribution of PIPs.
It is concluded that more intense interactions are needed by the three major stakeholders (Authorities, Industry and Investigators) in order to align on a common goal for clinical research in children.
References
Report on the survey of all paediatric uses of medicinal products in Europe. www/emea/europa.eu
Opinion and decisions on Paediatric Investigation Plans (PIPs). www/emea/europa.eu
PubMed Central homepage. www.ncbi.nlm.nih.gov/pmc/