Impact of the Clinical Trials Directive on the Research-Based Pharmaceutical Industry

Abstract

The clinical trial directive was first proposed in order to implement the requirements of the International Conference on Harmonisation (ICH) E6 on Good Clinical Practice (GCP)[1] into the European Legislation as a white paper in the early 1990s. It had a long and troublesome gestation before it appeared as final legal text in May 2001.[2] The scope was greater than originally envisaged and covered all aspects of the initiation and management of clinical research in the European Union (EU). There were many compromises required to reach consensus in the relevant bodies of the European systems. The directive text makes reference to many supporting guidelines and these have been delayed repeatedly. Due to delay in issuing the final guidelines, all Member State (MS) were unable to transpose the Directive’s schedule of May 2003 and, indeed, are still struggling to meet the final deadline for implementation of 1 May 2004. It has proved difficult both to plan and to manage at an operational level the changes required to cope with the new legislative requirements. There is concern that each MS may define elements of the Directive text differently and include or exclude different types of study e.g. non-interventional studies1 [1] (excluded from the Directive) in different ways; however, in principle, most studies will have to be performed under a Clinical Trial Authorisation (CTA). The primary aim of the Directive is to safeguard subjects taking part in clinical research and, therefore, applies not just to the pharmaceutical industry but also to academia. Anyone performing a clinical trial with an Investigational Medicinal Product (IMP) in Europe must comply with its regulations. In developing the Clinical Trials Directive and its guidelines, it would have been possible fundamentally to change the way in which Europe manages clinical research. Advances in the efficiency of regulatory and ethical review of clinical research can still be achieved. These potential opportunities are not being taken and it seems that the focus of elaborating procedural guidance has been on administrative control and bureaucracy rather than facilitating clinical research and thereby improving the competitiveness of clinical research in Europe. There will be no single decision across Europe for a multinational, multicentre study, but each involved MS will assess the application and reach its own decision, potentially creating conflict as well as duplication. A single, positive opinion per involved MS Ethics Committee (EC) must be received and ‘no grounds for non-acceptance’ communicated from the Competent Authority (CA). Concern remains that both the CA and EC will be looking at the same dossier and that no clear remit of each is yet published – again there is potential for ambiguity and conflict. This was delegated as a MS responsibility and is anticipated to differ as the national legislation and guidance evolves. The guidance and Directive introduces new terms and concepts into Clinical Trial Management as outlined in table I.