A guidance document setting out a Voluntary Harmonisation Procedure for the assessment of multinational clinical trial applications has been published by the EU’s Clinical Trials Facilitation Group (CTFG).

The CTFG was set up by the Heads of Medicines Agencies in the European Union to co-ordinate the implementation of the clinical trials Directive, 2001/20/EC. With the translation of this directive into national law, divergent practices have emerged in areas such as the distribution of responsibilities between competent authorities (CAs) and ethics committees, or the timelines for reviewing clinical trial applications, the Group points out.

There has also been divergence in the national assessment of multinational clinical trials (MN-CTs), which account for some 60% of trials in the EU. A study “might even be approved in one member state and rejected in another”, the CTFG says, adding: “Such situations not only may jeopardise the scientific value of clinical trial results in the case of country-specific modifications but are also hardly understood by the public, since the level of protection of clinical trial participants should be the same in all European countries”.

A conference on Directive 2001/20/EC, organised by the European Commission and the European Medicines Agency in October 2007, recognised the importance of maintaining the following general principles for the conduct of clinical research in the EU:

- The protection of trial subjects
- Ensuring high-quality research in the EU
- Contributing to a favourable research environment in the EU
- Bringing innovative medicines to patients as quickly as possible

In this light, the need to harmonise MN-CTs in Europe – “in order to ensure the protection of participants as well as the scientific value of clinical trials” – by harmonising the processes and practices of national CAs “has become a priority for the CTFG”, it notes.

As harmonising procedures for the assessment of clinical trial applications (CTAs) after they had been filed would be difficult and might even be counterproductive, in that it would add one more step “at the end of an already lengthy process”, the guidance proposes a Voluntary Harmonisation Procedure (VHP) that would occur before the initial phase of national assessment.

The guidance suggests an incremental procedure for harmonisation, with an initial pilot phase during which only MN-CTs meeting certain specified criteria (e.g., those involving an investigational medicinal product without a marketing authorisation in the EU) would go through the process.

Phase 1 of the proposed procedure would be a ‘pre-procedural’ or ‘request for a VHP’ step, in which the request for review of a planned CTA would be logged in the VHP system. Phase 2 would be an assessment step involving the review of the draft CTA by the national competent authorities (NCAs) of the participating member states. Phase 3 would occur at the national level, with formal clinical trial applications to all the concerned NCAs.

Further details on the Guidance document for a Voluntary Harmonisation Procedure for the assessment of multinational Clinical Trial Applications may be found on the website of the Heads of Medicines Agencies at www.hma.eu/uploads/media/VHP_public_CBB_22_Dec_08___hk_jan12.pdf.