EU law could improve ‘scandalous’ lack of clinical trial data reporting | Science
The global pandemic has put the spotlight on clinical trials, which test thousands of drugs and therapies each year. In Europe, however, enthusiasm for testing does not come with a zeal for reporting results to the public. A total of 3,846 European trials – nearly 28% of the 13,874 trials completed in the EU Clinical Trials Register (EUCTR) as of July 1 – had not published their results on the register, according to the latest data from the ‘EU Trials Tracker, set up by UK researchers in 2018 to expose lax reports. Public research hospitals and universities, not drug makers, are responsible for the vast majority of failures, which appear to violate European rules that require sponsors to publish their results within a year of a trial’s conclusion. .
“It is scandalous not to disclose the data, however disappointing they may be, to participating patients, to taxpayers in the case of public funding, and to all the other players,” laments Florian Naudet, meta-scientist at Rennes University Hospital. Naudet says undisclosed results can lead to wasted effort and missed signs of potential drug harms.
But Europe is getting more serious about enforcing reporting requirements. The European Medicines Agency (EMA) has stepped up reminders to trial managers, and a new trial register is expected to go live in January 2022, when national regulators will also have more power to enforce the rules. The changes come in line with signs of change in the United States, where many trial sponsors are also negligent: In April, the United States Food and Drug Administration (FDA) for the first time cited a violation of ‘a widely flouted US public reporting law. Till Bruckner, founder of TranspariMED, a UK-based advocacy campaign to improve reporting, hopes that soon he doesn’t have to berate trial leaders so much. “I’m sick of doing the job of regulators. “
Pharmaceutical companies, with the luxury of large compliance departments and seasoned reporting systems, are already taking the problem seriously. “It’s rare to see a large pharmaceutical company with underperforming outstanding performance, whether in the US or the EU,” says Nicholas DeVito, who heads the EU and EU trial trackers. the FDA at the University of Oxford.
Public testing centers are another story, however. Some researchers are unwilling to disclose negative results and believe they have the data, Naudet says. Others believe that publication of results in a journal meets the reporting requirement, although journal articles can arrive years later and are often not made public. Public centers have “a much harder time educating their investigators and putting systems in place,” says DeVito. “They have little incentive to improve if they don’t have to.”
Among the worst offenders, according to Bruckner, are the Paris Public Assistance Hospitals (AP-HP), which see themselves as the largest clinical trial center in Europe. It reported the results of only one of the 35 trials completed more than 12 months ago, according to the EU tracker. But Bruckner points out that the AP-HP’s reporting performance is probably even worse than that: more than 200 of the centre’s trials are listed on the EUCTR as ongoing, even though more than half of them have started over 10 years ago. “It’s inconceivable that none of them are late,” he said. AP-HP says in a press release Science that TranspariMED does not take into account its efforts for several years to “strengthen the transparency of ongoing studies and promote scientific integrity”.
The current rules stem from the 2001 European directives which Fergus Sweeney, head of the EMA’s clinical studies and manufacturing working group, calls “soft legislation”. Whether they represent a legal obligation or just a recommendation, it’s “cutting corners,” he says. Some nations seem to take advantage of this leeway. “According to the French regulations in force, there is no obligation to publish the results in the EU database”, explains Anne Metzinger, deputy director of the health research department at the CHU de Lyon. “So far our priority has been to publish both positive and negative results in peer-reviewed journals.”
In the Netherlands, argues Jessika van Kammen, director of research support at the University Medical Center Amsterdam (AUMC), it is sufficient for trial managers or sponsors to put the results in the Dutch trial register, managed by the Central Committee for Research Involving Human Subjects (CCMO). “It is not their responsibility to upload them to the EUCTR,” she adds. The CCMO website says that sponsors must also publish the results of drug trials in the EU database, but the AUMC does not follow this rule. “We see no benefit in doubling enrollment or doubling the administrative burden on researchers,” says van Kammen.
DeVito sees signs of change. Since the launch of the EU tracker in 2018, timely notification of results has increased from 50% to 72% of completed trials. Sweeney says the EMA has sent around 30,000 reminders to overdue test sponsors since 2018, another possible driver for improvement. Special advisories are issued for COVID-19 testing. “Some sponsors, mainly academics, were in fact unaware of their reporting obligation,” he says.
National regulators will have more advanced tools at their disposal with the launch of the EMA’s Clinical Trials Information System (CTIS), scheduled for January 2022. It will eventually replace the EUCTR portal after a transition period of 3 years, and put an end to the arduous registration process. trials in each participating country. Sponsors will download all trial data from start to finish. Relevant national regulators will review the data before the information is made public. “This is a unique, linear and straightforward process,” according to the EMA.
Once the CTIS is launched, a 2014 European regulation will come into force, allowing national regulators in the European Economic Area (the 27 EU Member States plus Iceland, Liechtenstein and Norway) to require disclosure of results. With the new regulations, “it is very clear that the sponsor is responsible for uploading the results,” Bruckner says. It will be up to governments to decide how national regulators should enforce the declaration and what penalties they should impose in the event of failure.
Denmark, known for its vigilant drug and testing regulation, could be a role model. It already has a law in place that allows authorities to impose fines or even jail those responsible for clinical trials who fail to meet deadlines for reporting results. In practice, the Danish Medicines Agency would file a complaint with the police, who would refer the case to the public prosecutor. That hasn’t happened yet, says Nanna Aaby Kruse, the agency’s quality assessment and clinical trials manager. She prefers recalls but does not rule out legal action. “We haven’t decided yet how long we will give the latecomers before we take legal action,” she said. “We always try to find the right balance between carrot and stick. “