The European Commission has issued a proposed regulation that would replace the existing clinical trials Directive while streamlining and further harmonising approval and reporting procedures, improving transparency and tailoring regulation to risk.

It comes after more than three years of debate and growing impatience with what is widely seen as a complex, bureaucratic and inconsistent environment for clinical research in the European Union.

The publication of the Proposal for a Regulation of the European Parliament and of the Council on clinical trials on medicinal products for human use, and repealing Directive 2001/20/EC was generally welcomed by the biopharmaceutical industry.

However, the European Federation of Pharmaceutical Industries and Associations (EFPIA) stressed that, for the new system to be truly effective, the integration of scientific assessment processes should be “pushed to its maximum operational level”.

The proposed regulation, expected to take effect in late 2016, can be read in full at  It will now be debated by the European Parliament and the Council, with final adoption of the new legislation not anticipated before 2014.

Binding impact

Couching the legislation as a regulation rather than a Directive will ensure the new rules, once finalised and adopted, will have an immediate and binding impact across the EU, avoiding the fragmentation and vagaries of interpretation that have plagued Directive 2001/20/EC.

The Commission framed the proposal explicitly as a spur to economic growth in Europe and an effort to stem the drift of clinical trials into emerging and other markets.

While Directive 2001/20/EC has ensured a high level of patient safety, divergence in its transposition and interpretation has “led to an unfavourable regulatory framework for clinical research”, contributing to a 24% decline in the annual number of clinical trial applications across the EU (from 5,000 to 3,800) between 2007 and 2011, the Commission stated.

Clinical research accounts for more than 20 billion euros of investment each year in the EU, it noted. According to John Dalli, European Commissioner for Health and Consumer Policy, the proposed measures could save 800 million euros per year in regulatory costs while boosting research and development throughout the Union.

“Patients in Europe should have access to the most innovative clinical research,” he commented.

“Clinical trials are crucial for developing new medicines and improving existing treatments. This is why today’s proposal significantly facilitates the management of clinical trials, while maintaining the highest standards of patient safety and the robustness and reliability of trial data.”

Simpler and quicker

Among the notable features of the Commission’s proposal are:

•    A simplified authorisation procedure that would allow for a “fast and thorough” assessment of a clinical trial application by all the Member States concerned as well as a single assessment outcome.

Individual Member States would be permitted to appoint the body or bodies in charge of assessing clinical trial applications, on condition that the assessment    were “fully independent and based on the necessary expertise”, the Commission notes.

    The new authorisation procedure envisaged in the draft regulation would revolve around:                                           

-    A harmonised authorisation dossier;                          

-    A ‘single portal’ for submitting clinical-trial applications, linked

to an EU database and managed by the European Commission;

-    A “flexible and swift” assessment procedure largely controlled by Member States;         

-    A clear mechanism for appointing a ‘reporting Member State’;          

-    Clear timelines with a “concept of tacit approval in order to ensure compliance”;                                       

-    A co-ordination and advisory forum to address issues that might arise in the authorisation procedure.  

 -   A clear distinction between “aspects where Member States co-operate in the assessment and aspects of an intrinsic ethical or national/local nature where the assessment is made by each Member State individually”.

•    Simplified reporting procedures that would spare researchers from having to file “largely identical” information on clinical trials separately with various bodies and Member States.                              

•    More transparency around patient recruitment for clinical trials and study results.

For example, while clinical trials authorised in the EU have been published in an official register ( since May 2011, the   proposed regulation would ensure that information on whether recruitment for a trial were ongoing would be publicly available.

There would also be more public access to trial results, whether positive or negative.                                       

•    Sponsors’ obligations would be better differentiated according to the risk posed by the trial to participants.

Acknowledging that academic studies account for around 40% of clinical-trial applications in the EU, the proposed regulation introduces the concept of a ‘low-intervention clinical trial’', where the additional risk to patients is negligible compared with receiving a treatment in normal clinical practice.

In these circumstances, the regulatory requirements would be “less burdensome and the timeline for authorisations shorter”, the Commission says.

First step

The EFPIA welcomed the Commission’s proposal as a “first step towards further co-operation in the clinical trials assessment process across the EU”.

It provides a “unique opportunity to create a competitive European medical research environment for the next 20 years capable of supporting the discovery and development of tomorrow’s treatments for the benefit of European patients”, commented EFPIA director general Richard Bergström.

The Federation also emphasised, though, that the new regulation, while ensuring patient safety remained paramount, must lead to an “effective, coherent and consistent EU environment”.

The key to making the system work, Bergström said, was a “workable administrative and scientific co-operation for large-scale clinical trials …. We call on the European Parliament and Member States to take a responsible, ambitious and pragmatic approach when debating the Commission’s proposal”.

Highly engaged

Alan Morrison, chair of the Regulatory Affairs Advisory Committee at the UK’s BioIndustry Association, said the BIA was “delighted” the Commission had adopted a legislative proposal that “should lead to more harmonisation, transparency and consistency in the approval and conduct of clinical trials across EU Member States, while maintaining high standards of patient safety and robustness and reliability of clinical data”.

The BIA had been “highly engaged over the last few years to get to this point” and was pleased to see the Commission had addressed as number of its key concerns in the proposed regulation.

For the Association of the British Pharmaceutical Industry, the Commission’s proposal provides “a unique opportunity to simplify and standardise the EU environment for conducting clinical research that, if we are ambitious, could enhance the development of medicines, whilst ensuring patient safety is protected”.

The number of clinical trials in both Europe and the UK has been declining over recent years, in part due to the complexity of the EU environment, the ABPI pointed out. This was a chance to “address the decline [and] improve patients’ access to the latest clinical research, while encouraging inward investment into the UK”.

The European Office of the UK's NHS Confederation’s called on EU decision-makers rapidly to agree the changes, saying the current Directive "places a huge bureaucratic burden on NHS organisations that want to get involved in clinical trials".

This is "wholly disproportionate, particularly for trials which are low risk", commented Office director Elisabetta Zanon.

"Not only is the UK economy losing out, but UK patients miss out on vital opportunities to benefit from the development of life-changing medicines."

The NHS Confederation has "long been pressing for changes to the existing Directive, and for an approach which gets right the balance between risk and safety", Zanon noted.