Implementation of the EU clinical trial regulation transforms the ethics committee systems and endangers ethical standards

The upcoming Regulation (EU) No 536/2014 on clinical trials on medicinal products for human use (Regulation), which will replace the current Clinical Trial Directive at the end of 2021, has triggered a significant reform of research ethics committee systems in Europe. Changes related to ethics review of clinical trials in the EU were considered to be essential to create a more favourable environment to conduct clinical trials in the EU. The concern is, however, that the role of the research ethics committees will weaken in at least some of the Member States because the new Regulation allows narrowing down the scope of ethics review as compared with the currently valid Clinical Trial Directive. Although the new Regulation may lead to faster approval procedures for clinical trials, which is especially relevant in the context of pandemics, high-quality ethics reviews integrating methodological aspects of a clinical trial should nevertheless be ensured. To maintain high research ethics standards as well as to foster measures to mitigate potential negative consequences of the reform, it is therefore of vital importance to start debating and sharing the reflections about the potential consequences of these transformations and trends as soon as possible.

Clinical trial supplies: investigational medicinal products (IMPs)

This chapter describes the procedures and records associated with accountability of investigational and non-investigational medicinal products (IMP and NIMP) used in clinical trials, to show that the drug has been labelled according to the regulations, stored in conditions to keep it stable, prepared and administered to the correct subjects in accordance with the protocol, has been fully accounted for and destroyed if unused. Manufacture of IMP is discussed together with methods of blinding. The role of the Qualified person (QP) is reviewed. The need for study drug accountability is discussed in context with the regulatory requirements (Clinical Trial Directive 2001/20/EC and in particular, GMP Directive 2003/94/EC Annex 13). The chapter explains what needs to be accounted for and describes the types of records including: labelling records, delivery and transportation, receipt, storage, preparation, dispensing and administration, unblinding records, reconciliation, returns and destruction. Discussions are included on protocol compliance, management of excursions resulting from incorrect storage conditions, management of dosing errors and documentation errors, expiry date re-labelling, drug recall and re-supply. Sections are included on considerations for non-commercial studies, GMP requirements for UK Phase I clinics and sites requiring a MIA (IMP) license.

The Implementation of Directive 2001/20/EC into Belgian Law and the Specific Provisions on Pediatric Research

The European Clinical Trial Directive (2001/20/EC) was implemented into the Belgian legal system by the Law of 7 May 2004 concerning experiments on the human person (LEH). Apart from implementing the European Directive, this law also broadens the scope of the Directive from interventional clinical trials to all medical experiments involving human persons. This article offers an overview of the requirements for involving minors in medical experiments that are captured in the LEH, illustrates the process of protocol review by an ethics committee, and discusses the dissimilarities between the LEH and the European Directive.

Legislation and Review of Medical Research with Minors in The Netherlands

In The Netherlands medical research with minors is regulated in the Medical Research Involving Human Subjects Act. During the legislation process in the Houses of Parliament in the 1990s the issue of non-therapeutic research with minors and incapacitated subjects was heavily debated. Stringent regulations were formulated for this type of research and the Act became operational in December 1999. In order to implement the Clinical Trial Directive 2001/20/EG, the Act was modified on several issues. However, the Act was not modified on the issue of non-therapeutic research with minors and incapacitated subjects. As a result at present the Dutch law is more restrictive on non-therapeutic research with minors than the EU Directive. Currently, discussion is ongoing to adapt the Dutch law in order to harmonize it with the EU Directive.