Science - USA (2021-07-16)

(Antfer) #1
268 16 JULY 2021 • VOL 373 ISSUE 6552 SCIENCE


he global pandemic has turned a spot-
light on clinical trials, which test thou-
sands 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 Tri-
als Tracker, set up by U.K. researchers in 2018
to expose lax reporting. Public research hos-
pitals and universities, not drugmakers, are
responsible for the vast majority of
the lapses, which appear to violate
European rules that require spon-
sors 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 tax-
payers 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 spon-
sors 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 ad-
vocacy 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 lux-
ury 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, how-
ever. Some researchers aren’t keen to dis-
close negative results and think they own the
data, Naudet says. Others believe publishing
results in a journal fulfills the reporting re-
quirement—even though journal articles can
come years later and are often not made pub-
lic. The public centers have “a much harder
time educating their investigators and setting
up systems,” DeVito says. “They have little in-
centive 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 perfor-
mance is likely even worse than
that: More than 200 of the cen-
ter’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 Euro-
pean 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 re-
search department at the University Hospi-
tal Center of Lyon. “Until now, our priority
has been to publish both positive and nega-
tive 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 reg-
istry, run by the Central Committee on Re-
search Involving Human Subjects (CCMO).
“It is not their responsibility to upload these
to the EUCTR,” she adds. The CCMO web-
site states that sponsors must also post re-
sults 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 re-
porting 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 tran-
sition period, and will end the arduous pro-
cess 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 in-
formation becomes public. “It is one, linear,
straight-through process,” according to EMA.
Once CTIS goes live, a 2014 European
regulation will take effect, empowering na-
tional regulators in the European Economic
Area (the 27 EU member states plus Iceland,
Liechtenstein, and Norway) to enforce the re-
porting 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 regula-
tion of drugs and trials, could be a model. It
already has a law on the books that allows
authorities to fine or even imprison clini-
cal 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.” j

Barbara Casassus is a journalist based in Paris.

By Barbara Casassus


European law could boost clinical trials reporting

New database and stricter enforcement could help end lapses in reporting results

of nearly 14,
completed trials
went unreported.


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