ABOVE: © ISTOCK.COM, SOLIDCOLOURS
According to the EU Trials Tracker, one-fifth of clinical trials run in the European Union do not report their results, with not even a brief summary of their findings posted in a register. This means negative results are not always made public, potentially distorting evaluations of an intervention’s efficacy and slowing medical research. It’s a problem that the Council of the European Union and the European Parliament aimed to solve in 2014 when they adopted the Clinical Trials Regulation (CTR)—a new set of rules governing clinical trial applications. Now, as of January 31, the CTR is finally in effect, and researchers are hopeful it will live up to its goal of improving transparency.
One of the key stipulations of the CTR is that it mandates reporting of study results within a year of a trial’s conclusion. The Regulation also aims to foster large, multinational collaborations by allowing applications for investigational medicinal products’ trials to be submitted through a single, central portal, regardless of the proposed trial location within the EU and the European Economic Area, rather than filed separately in each country where the trial is proposed to run.
“It’s unique in the world [and] gives [every trial] access to the European research environment with a population of over 400 million people now, and all the researchers, clinics, [and] hospitals who are there,” Fergus Sweeney, head of the Clinical Studies and Manufacturing Task Force at the European Medicines Agency (EMA), tells The Scientist.
“With time and as people get used to it, it will become easy for a researcher in Paris and [one in] Berlin to join together and run a trial, whereas mostly now, they tend to be in silos within each member state,” Sweeny adds. “So it’s really a major aim to extend multinational trials, whether they are big trials, which need a lot of patients, or in rare diseases.”
The eight-year delay between the CTR’s enactment and effective date stemmed from a need for new infrastructure, as the new regulation required a unified registry for clinical trials in the EU. Now, the new trial registration portal, called the Clinical Trials Information System (CTIS), has passed an external audit and is live, explains Sweeney, although sponsors for new trials are not obliged to use it until next year. The CTR stipulates that by the end of January 2025, all ongoing clinical trials must be transferred to the new registry. This applies to all trials of investigational medicinal products that are run in at least one member state of the EU or the European Economic Area.
In addition to enabling submission through the CTIS system, the regulation requires that decisions on trial applications incorporate both a review by the competent authority in each member state the trial will run in and an ethics committee opinion in each member state, Sweeney points out. “It is a single decision, and [then] the trial can then run in that member state. . . . It’s a one-stop shop for trial application.” Or, to put it into US research regulation terms, it would be like having the FDA Investigational New Drug (IND) application, Institutional Review Board (IRB) ethics approval application, and clinicaltrials.gov registration all filed and decided upon together, Sweeney says.
It’s a one-stop shop for trial application.
—Fergus Sweeney, European Medicines Agency
The new rules additionally require sponsors to publish a summary of trial results and a layperson’s summary to CTIS within 12 months of completing a trial (or within six months, if the trial was carried out in children).
Till Bruckner, founder of TranspariMED, an advocacy campaign to improve trial reporting, says he believes the new system will increase transparency, especially with regards to trial outcomes. “The importance of the registry is that it will consistently make results of every single trial public within a year. . . [which] accelerates medical process and reduces nonpublication of trial results.” He also says he hopes the portal itself makes the reporting process smoother. “With the old system, it was really cumbersome to upload results. . . . CTIS will make reporting easier—hopefully. We will know when the first trials register there and are due to report results.”
See “About Half of Clinical Trials Go Unreported in EU”
The CTR further stipulates that member states must establish effective penalties for noncompliance with reporting requirements, especially when it comes to information to be made public, Sweeney says. “As soon as the sponsor posts ‘start of recruitment,’ it’s in the public register,” he notes—something that wasn’t true with the old system. Then, when the researchers report that the trial is over, its end date also becomes part of the public record, he says. “Going through the single system offers enormous advantage over [the previous trial database] EudraCT from the transparency point of view, the completeness of the transparency, and its follow-up.”
Nicholas DeVito, a researcher at the University of Oxford who developed and runs the EU Trials tracker that monitors the data reporting of clinical trials in the EU’s old database, tells The Scientist that he is “eager to see how the enforcement and the preparation of results evolve, and we’ll certainly be keeping a close eye on that.” While the reporting of results was not automatically tracked within the old EU trials register, such an audit system is built into CTIS, Sweeney explains. “We can track these processes: both the sponsors are alerted—‘it’s time for you to submit your results’—and the member states— ‘sponsor X didn’t submit, 12 months has passed now.’ . . . Also, the public will be able to see when results should have been posted and if they are there or not.”
DeVito had hoped for a registry that is “a little bit more sophisticated at first glance, rivalling perhaps clinicaltrials.gov” in design and user experience. However, he says that the unified application process across the EU “will be a big help” as it establishes clear accountability and allows for easier tracking of compliance, especially for trials run in several member states, as a reporting member state will be designated and take the lead on trial application and monitoring.
While Brucker says that, overall, CTIS is an improvement, he points out that it only applies to trials for investigational medicinal products. “Medical devices and everything not in this category is overlooked, including trials of surgery or radiotherapy—any trial that doesn’t fit this narrow definition.”
