For decades, the U.S. FDA has uncovered misconduct in clinical trials but hidden it from the public, according to a new paper in JAMA Internal Medicine.
The study, by New York University journalism professor Charles Seife, looked at 78 publications resulting from trials where the FDA found serious misconduct, including “failure to protect the safety of patients” and data fakery. Only three of those publications mentioned the problems uncovered by the FDA. No retractions or errata were ever issued for any of them.
For example, in one of the three cases:
…data from several patients were excluded from the efficacy analysis because “site monitoring raised questions in regard to certain data at 1 study site.”65(p431) The FDA documents64 allege that none of the individuals enrolled at 1 study site had met the inclusion criteria and that the responsible researcher had fabricated chest radiographs of participants and committed other forms of misconduct.
(Reference 65 reported results of a trial Ivan wrote about several years ago, in coverage that raised some unrelated questions.)
The JAMA Internal Medicine article pulls exactly zero punches:
Conclusions and Relevance When the FDA finds significant departures from good clinical practice, those findings are seldom reflected in the peer-reviewed literature, even when there is evidence of data fabrication or other forms of research misconduct.
Seife also wrote a Slate piece, published concurrently with the paper, which was even more brutal, directly stating that the FDA actively covers up clinical misconduct:
That misconduct happens isn’t shocking. What is: When the FDA finds scientific fraud or misconduct, the agency doesn’t notify the public, the medical establishment, or even the scientific community that the results of a medical experiment are not to be trusted…The FDA has repeatedly hidden evidence of scientific fraud not just from the public, but also from its most trusted scientific advisers, even as they were deciding whether or not a new drug should be allowed on the market. Even a congressional panel investigating a case of fraud regarding a dangerous drug couldn’t get forthright answers. For an agency devoted to protecting the public from bogus medical science, the FDA seems to be spending an awful lot of effort protecting the perpetrators of bogus science from the public.
JAMA Internal Medicine wrote an editorial to accompany the paper (behind a paywall). It noted that the FDA is moving towards more transparency, though their practice of heavily redacting information makes investigative work slow going. Here’s an excerpt:
It is important to note that most FDA inspections are not classified as Official Action Indicated. Seife could not estimate the actual frequency of serious problems owing to the large number of records that were missing or unavailable. And he could not determine how often the violations found by the FDA could reasonably be expected to be acknowledged in an article or how often corrections or retractions were indicated. If the FDA documents had been more accessible and not heavily redacted, however, it is likely that Seife would have linked more published clinical trials to apparent research misconduct.
When the FDA identifies apparent research misconduct, it generally does not make a public announcement or, in the case of a published clinical trial, notify the journal that published the study. It is in the public interest for the agency to make available more information about its compliance and enforcement activities, and it has already begun to do so. In 2009, the FDA announced a transparency initiative; in 2010 and 2011 a task force issued draft proposals, including those to illuminate the agency’s compliance and enforcement activities.
Seife did not contact the journals for reactions, which he normally would have done, he tells us, because this was going in the peer-reviewed literature rather than the popular press.
(Full disclosure: Ivan and Charles are colleagues at NYU, and some of their mutual students helped gather the data for the article). We asked Seife about what it was like working with J-school students, and how the process of digging through the documents went:
One of the wonderful things about having a dozen or so bright students is that you can set them loose on a many-hands-light-work sort of assignment. Go out and find fraud, my pretties! *cackle* So all I had to do was point them in the right direction, and data began trickling in.
The tough part was gathering up all the data and validating it. One advantage we had was that we had no illusions that we’d be comprehensive; the redactions were sometimes way too extensive for us to have hope that we’d get everything. That knowledge kept us from spending too much time beating our heads against the wall trying to crack documents that simply wouldn’t be cracked.
We’ve reached out to the FDA for comment, but for now here’s the one they gave to Reuters. The FDA:
“. . . is committed to increasing the transparency of compliance and enforcement activities with the goal of enhancing the public’s understanding of the FDA’s decisions, promoting the accountability of the FDA, and fostering an understanding among regulated industry about the need for consistently safe and high-quality products.”
We’ve also reached out to COPE for some guidance on the ethics of all this, and will update if we hear back [See update below].
In the Reuters story, Seife agreed with JAMA Internal Medicine that transparency is increasing within the agency. However, he said,
I’m not sure you’ll ever get traction until there’s some incentive behind it.
Update 4:30 p.m. EST 2/11/15: COPE Chair Virginia Barbour got back to us about COPE’s role in this issue:
I had seen this paper and agree it has implications for the reporting of clinical trials.
I am not sure however, this is an issue just for or even primarily for COPE – the responsibility here would seem to me to lie with the authors, the institutions where the trials were undertaken and the funders of the studies – all of whom will presumably have been aware of the FDA findings in relation to the trials they are involved with.
My expectation would be that if such information is available the authors should report it in any article arising from the trial so as to ensure that the information is available to reviewers and editors, and ultimately if it is published and relevant, to readers. Editors should use this information in assessing the papers as should reviewers.