Concealing results from medical studies on humans will be banned
Norwegian researchers will soon be legally required to share the results of medical research on humans. But will the law be followed? In the United States, six out of ten studies break the law, without penalty.
The goal of medical research is to give doctors and patients useful knowledge about health care. Which treatments work? What are safe or harmful medications?
But what if we don't get to know the results from some of this research?
For decades, a number of studies from different countries have shown that scientists do not publish all their results.
They publish more often about successful experiments than about research results that didn’t show what they had hoped.
This can have serious consequences. It can make it seem like a medicine works better than it does. Or, even worse, dangerous drugs may be approved for sale in pharmacies.
And patients are exposed to the risk of participating in a research project for nothing.
Law enforcement should be a matter of course
A clinical study is medical research that involves humans.
The EU has since 2012 required the researchers who are responsible for these types of studies to share their results in the public European database the EU Clinical Trials Register (EUCTR) within one year. A 2018 study however, showed that only half of all studies were reported.
Norwegian research institutions and pharmaceutical companies aren’t yet obliged to follow these rules. But they will soon be required by law to share their results.
“This should be a no-brainer. This is so important to the public that it should be a law,” says Jan-Ole Hesselberg, head of the AllTrials campaign in Norway, a group that is working to ensure that all clinical trials are made public.
Waiting for new system
The Norwegian authorities have decided that the EU Clinical Trials Regulation-directive of 2014 will be incorporated into Norwegian law. It will probably take effect towards the end of 2021.
Norwegian authorities are waiting for the new European web portal CTIS, where researchers will both upload results and apply for permission to conduct research.
The portal was supposed to be ready some time ago, but there have been many delays, partly due to technical problems.
In the meantime, the Norwegian Medicines Agency strongly encourages researchers to use the EUCTR database, says senior advisor Ingvild Aaløkken from the agency.
“It is good that study results are made available to the public,” she says.
Norwegian researchers don’t publish all their results either, according to a 2017 review conducted by journalists at forskning.no.
Every fifth Norwegian clinical study was neither entered in a public, searchable research database nor published in a scientific journal.
"This is terrible," Ben Goldacre said at the time.
Goldacre is a researcher at Oxford University in England and is one of the founders of the international AllTrials campaign.
He is behind a new study which shows that requiring the publication of results by law doesn’t necessarily ensure that the law is followed.
Six out of ten violate US law
Since 2007, US researchers have been required to report their findings in the ClinicalTrials database within one year of completing the study in question. There is also a form for studies that had to be discontinued before they could be completed.
But six out of ten medical studies on humans broke this law, according to a study of more than 4,200 clinical trials. Most of these studies involved drug trials.
This is the first complete tally in the US after the law was tightened in 2017. Researchers have looked at studies that were due to be reported between March 2018 and September 2019.
The authorities do not follow their own law
The researchers who are least likely to comply with US law are those sponsored by the US government. In this case, government-sponsored researchers didn’t publish seven out of ten studies by the deadline.
"The fact that the US Government cannot comply with its own laws is especially concerning," Goldacre and colleagues wrote in an article in The Lancet magazine.
Violations of the law can result in fines of up to about EUR 10 000.
But as yet, no one has been punished for their offenses, as far as the researchers could determine. They believe their investigation clearly shows that the law is not being enforced.
The Norwegian authorities have not yet decided what the consequences will be if researchers break the law here.
Hesselberg from AllTrials in Norway views a legal requirement to publish with measured enthusiasm.
“It’s all well and good to have a law, but it must be enforced. That has been the problem in many of these cases,” he says.
He points out that the Norwegian Health Research Act already requires researchers to submit the results to the regional ethics committee that approved their project. Still, some researchers do not.
Although many US scientists do not report their results within a year, that does not mean they never deliver. Some report after the deadline, the new review shows.
Pharmaceutical companies and those who do many studies most often publish within the deadline.
It’s encouraging that experience seems to be helping, the researchers who did the study said.
Aaløkken from the Norwegian Medicines Agency is not surprised. Her impression from Norway is that researchers who rarely do clinical studies find the authorities' forms difficult to understand.
“The drug companies do these kinds of studies all the time, and have their own people working on these types of tasks. Researchers in academia often have to do it themselves,” she says.
“There’s probably more at stake for the companies as well. They have to do everything right to be allowed to market their product later,” she adds.
Non-compliance should be punished
Norwegian authorities should punish researchers who do not publish their results, Goldacre believes.
"These researchers should be named, blacklisted and not get more money for clinical research," he said when he visited Norway in 2016.
Goldacre is serious about the threats of publicly exposing people who don’t comply. In the new study, he and colleagues published the names of both universities and companies that have broken the law many times and those who follow it every time.
His website TrialsTracker is constantly naming research institutions — including from Norway.
Previously, TrialsTracker named the Norwegian University of Science and Technology as having conducted 124 eligible trials, of which 82 hadn’t been published. When contacted by a Norwegian university newspaper, Uniforum, NTNU conducted its own review and found the number of unpublished studies to be far fewer.
Have to hassle researchers
In Norway, for the time being, it is legal to refrain from publishing all research results.
But researchers must nevertheless send their results to the Norwegian Medicines Agency. These reports to the authorities are not made public.
One out of four did not submit a final report in 2006, the Norwegian Medicines Agency's own tally showed.
Nevertheless, more researchers than previously followed the rules after the Norwegian Medicines Agency directly contacted researchers and pharmaceutical companies to request reports. That suggests that it can help if agencies insist on the results, even if there is no punishment involved, Aaløkken says.
“But they have to understand the value of reporting,” she says.
Patients take the risk
Doing rounds of calling researchers is not a viable solution, says Hesselberg. Computer systems should send out reminders and automatically detect violations.
“It will take a lot of resources to call around and remind researchers who don’t do their job,” he says.
He himself has experienced this as program manager at Stiftelsen Dam, which distributes money for health research.
Not publishing the results of publicly funded research is unacceptable and wastes scarce resources, say researchers Erik von Elm and Joerg Meerpohl.
"Although autonomy and self-regulation are cherished in academia, they must be weighed against the ethical imperative of reporting results from research for which patients take risks," they wrote in a comment in The Lancet.
Translated by: Nancy Bazilchuk
N.J. DeVito et.al: «Compliance with legal requirement to report clinical trial results on ClinicalTrials.gov: a cohort study». The Lancet, January 17, 2020. DOI: 10.1016 / S0140-6736 (19) 33220-9. Summary.
E. von Elm & J.J. Meerpohl: «Trial results reporting: FDA Amendments Act Final Rule needs enforcement». The Lancet, January 17, 2020. DOI: 10.1016 / S0140-6736 (20) 30105-7. Summary.