When a bearded dude at a Brooklyn coffee house says he’s shopping his novel around to agents, no one expects to see it on bookstore shelves in their lifetime. When a scientist says she’s got a pile of data ready to publish, well, that seems like it should see the light of day. But it just as likely won’t.
New research suggests that nearly half of all clinical trials involving kids go unfinished or unpublished — either because the researchers lose interest in the work or take up more pressing projects, or, in some cases, because the companies that funded the studies don’t want the results to get out.
That news won’t come as a surprise to anyone who has followed the fate of studies in general. But it should catch the notice of the FDA: The pharma industry currently gets a special bonus, in the form of extended exclusive marketing rights, for testing their drugs in kids — a rule that was implemented to accelerate research into childhood ailments.
A subsequent law demands that researchers who conduct drug studies in kids post their findings on ClinicalTrials.gov, a federally run database. The registry however, is just a clearinghouse of raw information and represents the bare minimum for reporting data. Few, if any, people without a background in research are going to know how to use it or make sense of what it contains. That’s why publication of studies is so important.
And by not publishing these studies, drug makers and scientists put young patients at risk, particularly if those data reveal dangerous side effects or other adverse events from taking medications.
For the new analysis, the researchers, from Boston Children’s Hospital, looked at 559 randomized controlled trials in children that had been logged in ClinicalTrials.gov between 2008 and 2010. They found that 19 percent were discontinued early, and that 30 percent of the remaining trials were unpublished by September 2015, an average of five years after their completion.
The new findings are virtually identical to those from a 2013 analysis, which found that fewer than half of 600 studies plucked at random from ClinicalTrials.gov were published.
And industry money was a significant predictor of whether data would see the light of day. Studies that received industry funding were more than twice as likely as those with non-industry grants — such as government or foundation money — to be unpublished two years after the end of the project, and more than three times as likely after three years.
In other words, companies are much more likely than academics to run out the clock on results, perhaps because the findings aren’t favorable to their products or because corporate priorities shift over time. It’s a mixed picture, though, when you look beyond just pediatric medicine. Companies are actually slightly better at depositing data in registries overall, according to STAT’s own analysis of the issue.
It’s unclear why researchers don’t publish, although a 2014 paper in PLOS One found that the most common excuse scientists gave was a “lack of time or low priority.” The “file drawer problem” — “Oh, those results aren’t interesting enough for a prestigious journal that can help our careers” — is a real one.
Enough already, say the organizers of AllTrials, a push to get all studies registered, and all data published. “Millions of volunteers have participated in clinical trials to help find out more about the effects of treatments on disease, yet that important ethical principle about reporting has been widely ignored,” say the founders of the initiative, which launched in January 2013. “Information on what was done and what was found in these trials could be lost forever to doctors and researchers, leading to bad treatment decisions, missed opportunities for good medicine, and trials being repeated.”
Of course, we know that some researchers will fight tooth and nail to keep their data private, choosing instead to build a wall and make the people asking for data to pay for it. But when even drug company titans see the benefits of putting it all out there, shouldn’t everyone?
I disagree that:
http://www.fapesp.br/eventos/2012/03/howtowrite/daniel.pdf Sincerely, Mable
My experience of small studies has been that many academics have a view that they should obtain the maximum output for minimum effort. So someone else designs the study and looks after ethics, someone else collects the data, someone else conducts the analysis and someone else writes the paper. So when it is company sponsored research they can easily prevent publication simply by not providing support for the analysis or the publication.
I can understand at times why they may not be interested. For example a drug may be about to die, based on very poor performance in a trial. If it is never to be used than there isn’t much point. Then they should have an alternative process that allows disseminating results.
I would argue that all clinical trial reports should be released. They have very little that could be kept in confidence (sometimes they do describe a testing methodology or similar) and that could be redacted leaving the results intact.
The results of clinical research should not be kept secret. You will get no argument on that point from anyone. But this article largely repeats the mildly paranoid arguments of recent publications that were titled and promoted for maximum clicks.
Many, many research projects produce largely anticipated results that are reassuring to researchers, sponsors and regulators but of almost no interest to any journal. Even articles of little interest and potential benefit require a great deal of work by the author, his institutional reviewing bodies, one or more journal’s executive editors, peer reviewers, some sort of copy editor, and someone to put the work in final “typeset” format. This is not the labor of one individual for one afternoon. Some degree of judgement must be exercised at all levels over what actually gets submitted and published.
The ClinicalTrials.gov repository is the ideal answer for this and researchers who haven’t taken advantage of it should be encouraged to do so. But a great deal of the cry, “Free the data!” comes from those seeking attention, press interviews, or easy access to data without the inconvenience of proposal writing, IRB review, regulatory negotiation and approval, patient recruitment, hours in the clinic working with actual patients, and data collection and analysis.
However tweet-worthy the implications of conspiracy and greed may be, simple limitations of funds, human effort, and daylight hours are more likely responsible for data trapped in a drawer. The arguments in this article and its immediate antecedents are correct but crucially incomplete.
I think the point is that NEGATIVE results need to be published, but are almost always buried. Newspapers and journals get very excited about “new discoveries”, but are not very excited about replication studies that invalidate the “new discoveries” that they prematurely reported on as sure things. There is a natural incentive to publish validating studies and not to publish contradictory studies, especially when monied interests get involved. It seems to make sense that ALL trial data should be made available, if we care even vaguely about being scientific. After all, you can have three dozen confirmatory studies and one solid contradictory one can bury a theory completely. Negative findings are MORE important than positive ones, because they (or their absence after multiple attempts to replicate) are what ultimately provide scientific certainty.
4 articles that may be of additional interest on mechanisms to formulate ways to increase data sharing of trial data-
http://www.nejm.org/toc/nejm/375/5
NEJM August 4, 2016 Vol. 375 No. 5
PERSPECTIVES
Pp: 401-403 Strengthening Research through Data Sharing, E. Warren
Pp:403-405 The Yale Open Data Access (YODA) Project — A Mechanism for Data Sharing, H.M. Krumholz and J. Waldstreicher
Pp: 405-407 Toward Fairness in Data Sharing, The International Consortium of Investigators for Fairness in Trial Data Sharing
and: Sharing Data from Cardiovascular Clinical Trials — A Proposal
The Academic Research Organization Consortium for Continuing Evaluation of Scientific Studies — Cardiovascular (ACCESS CV)