Eight Years Later, Europe’s ‘New’ Clinical Trial Rules Finally Come into Force
Formal compliance with EU’s Clinical Trials Regulation takes effect, designed to speed up the application and approval of studies.
There are probably very few readers of this site who are not by now aware that, as from today, arguably the biggest change ever in European rules on clinical trials has come into effect. The EU’s Clinical Trials Regulation (CTR) has been the subject of extensive comment over the last eight years, since the underlying legislation was adopted. Its aim of simplifying and easing clinical trial approvals across Europe is widely seen as valuable, and in official circles is being celebrated today. But it is perhaps worth noting that not everything is going to get easier, and not right away.
For a start, the opportunities for streamlining applications and procedures are accompanied by plenty of new obligations that sponsors must comply with. Many relate to tight and strict deadlines for reporting and for providing the authorities with notifications or replies to questions—and in many cases the penalty for non-compliance is that the application will lapse. The details of all these provisions have been neatly—and more comprehensibly—summarized in a note compiled by the European Commission and published to coincide with this momentous occasion.1
The tightness of the deadlines is easily judged: for instance, once a clinical trial approval has been granted and the study has started (defined as the start of recruitment), sponsors have just 15 days to notify this. The same deadline for notification applies to the first visit of the first subject, the end of recruitment, any restart of recruitment, and the end of the trial (defined as the last visit of the last subject in any of the participating member states). Any temporary halt of the trial, its resumption, or its early termination fall under the same obligation. Any breach of the protocol likely to affect safety rights of the subject or the reliability of the data must be reported within seven days, and the seven-day limit also applies to unexpected events—except for serious adverse events, which must be reported within 24 hours
Still more constraining, a new deadline of one year from the end of the trial applies to the filing of a summary of results, accompanied by the novel concept of a laypersons summary. And once a marketing authorization has been granted on the product, a clinical study report must be submitted.
It may be of interest to sponsors beyond Europe that where the provisions of the regulation on good clinical practice differ from those of the International Council for Harmonization of Technical Requirements for Pharmaceuticals for Human Use, the rules in the EU regulation prevail.
Naturally, there is satisfaction in the emergence at last of a system allowing for a single EU application to be made for a clinical trial that can lead to an approval valid across all the member states. Similarly, many sponsors see as helpful the obligations that are also placed on the authorities. In contrast to the weeks, months, and even years that it has often taken to obtain a decision on an application in just one country, a tacit approval now underlies the system. Broadly speaking, once the EU level procedure has been completed, each member state has to inform the applicant of the result within just five days. Where any of these new deadlines are missed by a member state, the application is deemed to be accepted.
The perennial European Union problem of its very diversity still, of course, tends to dampen hopes for speedy compliance by the authorities. Cristian Busoi, a Romanian physician who heads one of the most influential committees in the European Parliament, today lamented the continuing tendency of different countries to interpret common rules in their own way—which he sees as an obstacle to clear implementation of the CTR. The main drug industry lobby group in Europe, the European Federation of Pharmaceutical Industries and Associations (EFPIA), also greeted the general jubilation with some admonitory comments on “initial problems,” some requiring “extensive work to achieve a resolution.” It urged a focus on “further developing and enhancing the usability and functionality of the system,” which it says “is necessary for the effective conduct of clinical trials and for the EU to remain attractive for clinical research.” In particular it highlighted a lack of alignment of member state requirements, and situations where member states take different approaches to reviewing trials that need to be transitioned to the new system.
