A single EU submission followed by a coordinated assessment procedure is the European Commission’s current preferred option for clinical trial applications across the European Union, according to a new concept paper on planned revisions to the Clinical Trials Directive.

The concept paper is the latest stage in overhauling the much-criticised Directive 2001/20/EC, after the Commission received more than 100 responses to the full public consultation it launched in October 2009. The paper has been released for comment by 13 May 2011.

It is not intended as a re-run of the public consultation, the Commission stressed. Rather, the paper asks for further input in the form of “more concrete ideas on the issues that have been presented in a rather general way during the 2009/10 consultation”.

 Topics that were explored extensively during the 2009/10 consultation have not been put forward for more discussion at this stage.

The concept paper includes ‘preliminary appraisals’ of what appear to be the most suitable options for addressing key concerns about Directive 2001/20/EC, based on the current state of the impact assessment for the legislation.

It is also a way of verifying with stakeholders the core data used to evaluate the potential impact of the various policy options.

The section on clinical trial applications suggests three options for avoiding the current duplication and divergence associated with submitting largely identical information on proposed clinical trials in the EU to a number of Member States.

These options are:

• A single submission through an ‘EU portal’, to be administered by the European Medicines Agency, followed by separate assessments in the Member States involved. The Commission’s preliminary appraisal is that a single submission would greatly reduce the administrative burden on trial sponsors but that the difficulties created by independent Member State assessments would remain if this submission were followed by separate assessments. 

• A single submission followed by a central assessment, to be conducted by a scientific committee comprising representatives of all the Member States. The concept paper suggests this option would be both inappropriate and impracticable, as:    

- It would take insufficient account of “ethical, national and local perspectives” in the Member States, for which a parallel national procedure would need to be established.     

- The “sheer number” (around 1,200) of multinational clinical trials each year, plus all of the associated substantial amendments, would make centralised assessment very difficult.   

- Not all of the Member States would need to be involved, as very few clinical trials are rolled out in more than five or six.

• A single submission followed by a ‘coordinated assessment procedure’ (CAP). In this scenario, the CAP would be modelled to some extend on the decentralised procedure for marketing authorisations of medicines in the EU, “while having a stronger element of joint assessment by the Member States concerned”, the concept paper explains.

 It would include a ‘Reporting Member State, which would lead the assessment  of the clinical trial application; would have limited roles for the Commission and  the European Medicines Agency; would lead to ‘single decision’ per Member  State; and would address only selected aspects of the clinical trial application  (ethical issues, in particular, “clearly fall within the ambit of Member States and  should remain there”, the concept paper comments).

 A CAP, the Commission believes, “could offer a sufficiently flexible approach”.  It would allow for a joint assessment without a “cumbersome” committee  structure, while taking into consideration national practice and respecting Member  State autonomy on ethical issues.

Other sections of the concept paper deal with:

• Introducing a more harmonised, risk-adapted approach to the procedural aspects of clinical trials. This might be achieved by:

- Limiting the scope of Directive 2001/20/EC through enlarging the definition of non-interventional trials not subject to the legislation, or excluding from its ambit trials by academic/non-commercial sponsors.   

- More precise and risk-adapted rules for the content of the application dossier and for safety reporting.

- Clarifying the definition of ‘investigational medicinal product’ and establishing rules for ‘auxiliary medicinal’ products used in the context of clinical trials. 

- Amending insurance/indemnity requirements for clinical trials based on the level of risk involved, or introducing optional indemnisation by a Member State for trials conducted on their territory.    

- Revising the concept of a ‘single sponsor’ responsible for a clinical trial vis à vis the national competent authority and the relevant ethics committee. 

- Amending, under particular circumstances, the timing of informed consent procedures for emergency clinical trials.

• Ensuring compliance with Good Clinical Practice in clinical trials conducted in ‘third’ countries (e.g., through further support for capacity-building in third countries where the regulatory framework for clinical trials, and its enforcement, are weak).

The full concept paper may be found on the European Commission’s website at: http://ec.europa.eu/health/files/clinicaltrials/concept_paper_02-2011.pdf.