Clinical Trial Application in Europe: What Will Change with the New Regulation?

Abstract

The European framework surrounding clinical trials on medicinal products for human use is going to change as demonstrated by the large debate at European institutional level. One of the major challenges is to overcome the lack of harmonisation of clinical trial procedures among countries. This aspect is gaining more and more importance, considering the increasing number of multicentre and multinational studies. In this work, the actual European rules governing the Clinical Trial Application have been analysed throughout the different steps including the registration of the trial in the European database; the preparation of documents to be submitted and their contents; the preparation of documents related to the information and consent process; the submission to competent bodies. Specific issues related to paediatric research and trials involving non EU/EEA countries have been addressed as well. Results reveal that the European legislation offers a well defined set of European rules covering different aspects of a Clinical Trial Application. However, these are not suitable to meet the challenges from multicentre and multinational clinical studies. A stronger set of rules, such as is available in a composite European Regulation has been adopted and is expected to harmonise practices and enable sponsors to carry out well conducted trials. But will the new regulation overcome the existing criticisms of Directive 2001/20/EC?

The ethical framework for performing research with rare inherited neurometabolic disease patients

“…However, as underlined in this work and in line with previous considerations [ 37 ], they have a poor legislative power and are implemented only partially in the regulation recently released [ 28 ].…”

“…For paediatric trials, the assessment must take into account PDCO opinions on Paediatric Investigation Plans (PIPs) and must be carried out by ethics committees with paediatric expertise or seeking advice from experts in the field taking into account the risks and benefits of research and other aspects such as the study design, the use of placebo and the monitoring of safety during and after the trial. This represents an important achievement from the ethical point of view and in consideration of the protection of children’s rights [ 37 ]. However, uncertainties still remain on how national ethics committees and the PDCO will interact and what would happen if the PDCO and the ethics committee opinions differ [ 36 ].…”

Study factors associated with the incompletion of clinical trials that include pediatric patients: a retrospective analysis of the European Clinical Trials Database and a lesson from the European region

“…International cooperation for clinical trials that target small populations, such as rare disease or pediatric drug development, should be investigated further. Previous studies of EU-based trials have illustrated the importance of harmonization in clinical trial procedures where the trials conducted are necessary for pediatric clinical trials, given the rise of multicenter and multinational research [17]. It was reported that the key challenge these trials faced was overcoming the lack of harmonization of the status of several procedures across different countries.…”

Value of substitute consent and autonomy of research participants in Regulation (EU) No 536/2014

“…[6] The proportionality of acceptable and possible risk-to-benefit ratio is currently determined by a declaration of will of the research participant, i.e. constructs of informed consent [11,12,13,14].…”