Gillian Rea, solicitor at Dublin firm Baily Homan Smyth McVeigh, writes on changes to the legal framework of clinical trials in the European Union.

When introduced in May 2004, the EU Directive 2001/20/EC governing the trialling of medicinal products for human use (the Directive) imposed standards to improve both the safety of participants in clinical trials and the quality of the generated data. It was at the time considered to be an important step towards the harmonisation of laws in the EU.

The Directive however was not without its criticisms. Because of the very nature of its status as a directive, each member state was required to individually enact laws to implement it. Subtle differences between the various member state enactments of the Directive have at times led to patchy application of its provisions across the EU. From a more procedural perspective, the provisions of the Directive resulted in a requirement for multiple submissions of clinical trial applications for a multi-state trial.

The European Commission initially published the proposal for the EU regulation 536/2014 on clinical trials on medicinal products for human use (the Regulation) in July 2012. The Regulation is to replace the Directive and remedy its shortcomings. However, to date, its entry into force has been hampered by significant delays in finalising certain new technology required to enact particular provisions of the Regulation.

That being the case, the Regulation will herald a number of key changes in the clinical trial space when introduced into law. While its scope is relatively unchanged (it continues to cover interventional clinical trials with medicinal products for human use), certain provisions of the Regulation will change the landscape for clinical trials in the EU:

1) National Implementation vs Direct Effect

A most notable difference between the Directive and the Regulation is the very nature of the legislation involved. A directive is a legislative act that set out a number of goals that all EU member states have to achieve individually through their own national legislation. The Regulation on the other hand will be a binding act, immediately applicable and enforceable throughout the EU once it comes into law (subject to certain transition period provisions for ongoing clinical trials).

2) Single Submission to all Member States

Under the Regulation, the submission of a multi-jurisdictional clinical trial application will now only require one single regulatory authority and ethics committee submission. The submission will be made to all member states in which the clinical trial is to be conducted via a new EU portal. The sponsor will propose one of the concerned member states to act as the “reporting member state” and all responses will be coordinated. This will hugely cut down on the time and administrative input required by sponsors and clinical research organisations in the submission process.

3) New Category – Low-Interventional Clinical Trial

The Regulation includes a new category of trial which is subject to lower clinical scrutiny, where the investigated medicinal product is already market authorised or, if not used according to market authorisation, is used in a way that is supported by published scientific evidence.

4) Informed Consent

A number of new provisions on informed consent are introduced. The Regulation formally states the components of a valid informed consent and specifically points out that the patient must be given sufficient time to consider, ask questions and must also be given a copy of the signed form of consent. It also separates out the consent requirements into various groups, for example minors, pregnant and breastfeeding women, incapacitated people and persons deprived of their liberty.

EU portal and EU database – The Innovation and the Delay

The key pieces of innovation heralded by the Regulation are the EU portal and the EU database.

Once established, the portal will be the go-to place for submissions of all clinical trials carried out in the EU. It will offer a single electronic entry point with all information submitted being stored in a public database, significantly cutting down on costs, time and admin. The portal will be controlled by the European Medicines Agency (EMA).

The EU database will disclose all relevant information on ongoing and completed trials and will be publically accessible - dramatically increasing transparency in the clinical trial space. Information will only be protected from this disclosure if it relates to: (i) the processing of personal data, (ii) commercially confidential company information or (iii) confidential communications between member states.

A completely new departure, the EU portal and the EU database have the potential to revolutionise the management of clinical trials. However the significant technical complexities in perfecting the functionality of the portal and database have consistently pushed back the enactment of the new Regulation. The timeframe for entry into force is now early or mid-2020. The portal and database will need to be tested and audited by the EMA management board to ensure the system meets all requirements before the Commission can publish the notice in the Official Journal of the EU to commence the entry into law of the Regulation. Considered opinion is that the date could be pushed back yet again before we see this Regulation come into force.

Conclusion

Undoubtedly, sponsors proposing to conduct multi-state clinical trials in the EU will be the significant beneficiaries once the Regulation enters into force. The introduction of the single submission system will significantly reduce the costs and administrative burden associated with such trials while increasing their efficiency. However the generally increased harmonisation and transparency brought in by the Regulation will benefit sponsors, participants and the health of the patient population in general.