The Public Hospitals of Paris are a world-leading clinical trial center, but they are laggards at reporting trial results.
Emile LUIDER/REA/Redux
The global pandemic has turned a spotlight on clinical trials, which test thousands of drugs and therapies each year. In Europe, however, the enthusiasm for trials is not matched with a zeal for reporting the results to the public. A total of 3846 European trials—nearly 28% of 13,874 completed trials in the EU Clinical Trials Register (EUCTR) on 1 July—had not posted their results on the register, according to the latest data from the EU Trials Tracker, set up by U.K. researchers in 2018 to expose lax reporting. Public research hospitals and universities, not drugmakers, are responsible for the vast majority of the lapses, which appear to violate European rules that require sponsors to post their results within 1 year of a trial’s conclusion.
“It is scandalous not to disclose the data, however disappointing, to the patient participants, to taxpayers in the case of public funding, and to everyone else involved,” says Florian Naudet, a metaresearcher at the University of Rennes hospital in France. Naudet says undisclosed results can lead to wasted efforts and missed signs of drugs’ potential harms.
But Europe is getting more serious about enforcing the reporting requirements. The European Medicines Agency (EMA) has stepped up reminders to trial leaders, and a new trial registry is set to come online in January 2022, when national regulators will also gain more power to enforce the rules. The shifts dovetail with signs of change in the United States, where many trial sponsors are also remiss: In April, the U.S. Food and Drug Administration (FDA) for the first time cited a violation of a widely flouted U.S. public reporting law. Till Bruckner, founder of TranspariMED, a U.K.-based advocacy campaign to improve reporting, is hopeful that, soon, he won’t have to chide trial leaders so much. “I’m sick and tired of doing regulators’ jobs.”
Pharmaceutical companies, with the luxury of large compliance departments and seasoned reporting systems, already take the issue seriously. “It is rare to see a major drug company with anything less than sterling performance, in either the U.S. or EU,” says Nicholas DeVito, who runs EU and FDA trial trackers at the University of Oxford.
Public trial centers are another story, however. Some researchers aren’t keen to disclose negative results and think they own the data, Naudet says. Others believe publishing results in a journal fulfills the reporting requirement—even though journal articles can come years later and are often not made public. The public centers have “a much harder time educating their investigators and setting up systems,” DeVito says. “They have little incentive to improve if they are not forced to.”
Among the worst offenders, Bruckner says, is the Public Assistance Hospitals of Paris (AP-HP), which calls itself the largest clinical trial center in Europe. It has reported results for just one of 35 trials completed more than 12 months ago, according to the EU tracker. But Bruckner points out that AP-HP’s reporting performance is likely even worse than that: More than 200 of the center’s trials are listed on EUCTR as ongoing, even though more than half of them began more than 10 years ago. “It’s inconceivable that none of them are overdue,” he says. AP-HP says in a statement to Science that TranspariMED does not take account of its efforts for several years to “strengthen transparency of studies in progress and promote scientific integrity.”
The current rules stem from 2001 European guidelines that Fergus Sweeney, head of the EMA clinical studies and manufacturing task force, calls “soft legislation.” Whether they represent a legal obligation or merely a recommendation is “splitting hairs,” he says. Some nations seem to be taking advantage of that wiggle room. “According to current French regulations, there is no obligation to post results in the EU database,” says Anne Metzinger, deputy director of the health research department at the University Hospital Center of Lyon. “Until now, 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 Amsterdam University Medical Center (AUMC), it is sufficient if trial leaders or sponsors put results in the Dutch trial registry, run by the Central Committee on Research Involving Human Subjects (CCMO). “It is not their responsibility to upload these to the EUCTR,” she adds. The CCMO website states that sponsors must also post results of medicines trials in the EU database, but AUMC does not follow that rule. “We see no advantage in double registrations or in doubling researchers’ administrative burden,” van Kammen says.
DeVito sees signs of change. Since the launch of the EU tracker in 2018, timely reporting of results has risen from 50% to 72% of completed trials. Sweeney says EMA has sent out about 30,000 reminders to overdue trial sponsors since 2018, another possible driver of improvement. Special notices go out for COVID-19 trials. “Some sponsors—mostly academic—were actually unaware of their reporting requirement,” he says.
National regulators will have sharper tools at their disposal with the launch of EMA’s Clinical Trials Information System (CTIS), scheduled for January 2022. It will eventually replace the EUCTR portal after a 3-year transition period, and will end the arduous process of registering trials in each participating country. Sponsors will upload all trial data, from start to finish. The relevant national regulators will review the data before the information becomes public. “It is one, linear, straight-through process,” according to EMA.
Once CTIS goes live, a 2014 European regulation will take effect, empowering national regulators in the European Economic Area (the 27 EU member states plus Iceland, Liechtenstein, and Norway) to enforce the reporting of results. With the new regulations, “The onus is very clearly on the sponsor to upload the results,” Bruckner says. It will be for governments to decide how the national regulators should enforce reporting and what penalties they should impose for lapses.
Denmark, known for its vigilant regulation of drugs and trials, could be a model. It already has a law on the books that allows authorities to fine or even imprison clinical trial leaders who do not meet deadlines for reporting results. In practice, the Danish Medicines Agency would lodge a complaint with the police, which would turn the case over to the public prosecutor. This hasn’t happened yet, says Nanna Aaby Kruse, the agency’s head of quality assessment and clinical trials. She prefers reminders but doesn’t rule out legal action. “We haven’t yet decided how long we will give stragglers before taking legal action,” she says. “We are still trying to find the right balance between the carrot and stick.”
Source: Science Mag