Masterstudiengang "Drug Regulatory Affairs"

Master-Thesis

European and national (German) databases with regard to clinical trials involving children

Houmyra Kazimie (Abschlußjahr: 2009)

Background:
A large majority of medicinal products has only been tested on and authorised for use in adults. To date, the development of medicinal products for children has been neglected in Europe. Thus, many medicinal products are administered in the course of paediatric pharmacotherapy that have not been tested for efficacy and safety for the age group concerned, neither in terms of the indication in each case or the dosage administered. As a result, there is a lack of pharmaceutical forms suitable for the relevant age-group, as well as evidence-based recommended dosages and information on possible adverse effects and interactions with other medicinal products. Only since the entry into force of EC Regulation 1901/2006 on medicinal products for paediatric use of 12 December 2006 has a re-think become urgently necessary. This is linked with the need to develop and expand special databases for relevant research on paediatric clinical trials. The objective of this Masters thesis is to present the European (EudraCT, Eudravigilance) and national (PharmNet.Bund-CT, UAW) databases and other sources of information on paediatric clinical trials. The specific possibilities for data collection and research are evaluated. Based on this, suggested solutions will be developed and outlined as to how the existing databases and research options with regard to paediatric clinical trials could be improved.

Methods:
The design, structure and research options in the existing European and national databases were examined. In addition, other sources of information on paediatric clinical trials were evaluated. In the course of specific searches, research was carried out on exemplary paediatric clinical trials in the European (Eudravigilance / EudraCT) databases and the national UAE database and the consistent availability of data was assessed.


Results:
Version 6.0 of the EudraCT database does not feature a statistics tool. Above all the Paediatrics Regulation (Regulation (EC) No 1901/2006) has not been implemented in the form of new data fields that make it possible to define in more detail findings from reports in the field of paediatric trials by using selected fields. In connection with the implementation of the Paediatrics Regulation new data fields will be added in future. With regard to PharmNet.Bund-CT additional development stages are also planned. This further development corresponds analogously to the standards of the EMEA database on Clinical Trials (EudraCT). As regards transparency, in 2010 the data in defined fields for all studies contained to date in EudraCT (excluding PhaseItrials in adults) are to be made publicly available.

A common research problem of the UAE database is the absence of the internal BfArM submission number, without which it is difficult to clearly allocate cases to specific clinical trials. The Eudravigilance database does not have search fields for EudraCT-Nos. beginning with 2008. There is no way of restricting the search according to specific criteria, such as Protocol Code, Full Trial Title or IMP. With regard to paediatric clinical trials, a further issue is that children/legal guardians are often unable to satisfactorily describe UAEs.

The example searches showed a level of records of UAEs in paediatric clinical trials in the UAW database and the Eudravigilance database in comparison to the EudraCT database. The analysis of the Eudravigilance and UAW databases demonstrates that data collection is often limited. This finding can also be attributed to underdeveloped data collection systems.
A large number of different clinical trial registers and register databases were identified. These provide users with extensive scope for research and information.

Conclusions:
Prompted by the new regulatory requirements with regard to clinical trials in children, the relevant databases have become considerably more important.

In order to maintain a valid data basis for the EudraCT database and PharmNet.Bund-CT, the provisions of the Regulation on medicinal products for paediatric on obligatory entries into EudraCT use must be transposed into national rules (e.g. the GCP Ordinance). Here it is expressly provided that information on subsequent amendments and all stops to the study (regular and irregular) must be added. Currently, ethics committees have no access to the EudraCT database and PharmNet.Bund-CT. For paediatric clinical trials in particular it must be ensured that negative assessments by the ethics committee are recorded in these databases. With regard to the integration of clinical trials involving children into the EudraCT database the new provision on monetary fines set forth in Section 97 AMG is important. The aim is to improve the available information on the various paediatric populations and to increase transparency. If the EudraCT search function is improved, the research fields will also have to be expanded. In this connection, language barriers in particular must be taken into account (English language applications / multilingual text fields). The research carried out in the course of this thesis in the relevant databases also show that, to date, it has not yet been possible to achieve harmonised data collection method and a uniform data quality at the EU level and that this will prove to be a great challenge in future for all those involved in the process. This may, however, result in improvements in the safety of medicinal products for paediatric use.

Pages: 82