Research Misconduct Identified by the US Food and Drug Administration
According to a recent article published in JAMA Internal Medicine, 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.
Now, I know what you’re thinking…. that I’m just quoting the conclusion from the abstract and hijacking title of the article without actually reading the full text. So let’s go over the full text together shall we?
As part of the drug approval process, the US Food and Drug Administration (FDA) regularly inspects clinical trial sites involved in FDA-regulated research to determine the degree to which these sites conform to regulations. They are basically allowed to audit any and all aspects of a clinical trial including the data itself, if they see fit.
As a result, the FDA inspections can result in three outcomes.
- No action indicated (no substantial violations)
- Voluntary action indicated (inspectors have found violations, but not serious enough for sanctions)
- Official action indicated (OAI) (inspectors have found violations enough to warrant regulatory action)
This trial searched through an FDA database containing the results of some of its inspections and looked for results that contained an OAI. To obtain the documents, they had to file a Freedom of Information Act request. Their search resulted in 421 OAI-rated inspections. Next, the researchers tried to find trials in which enough data was not redacted to the point where they could identify the actual clinical trial with the site of inspection. When they were able to make this connection, they reviewed the trials, if published, to see if there was any written acknowledgment about the violations identified by the FDA.
There were approximately 600 clinical trials mentioned in the documents they gathered; owing to redactions, most of these trials could not be identified. However, in some cases, key information was not redacted from the documents, allowing them to identify 101 trials in which at least one clinical trial site received an OAI grade on an inspection. Of those 101 clinical trials, we identified 68 for which results had been published in the peer-reviewed literature, resulting in a total of 95 publications. 57 trials had sufficient data for them to prove a link between the trial and a violation, the rest had too much missing data to draw a firm conclusion.
In 22 of these trials, the FDA cited researchers for falsification or submission of false information; in 14 for problems with adverse events reporting; in 42, for failure to follow the investigational plan or other violations of protocol; in 35 for inadequate or inaccurate recordkeeping; in 30, for failure to protect the safety, rights, and welfare of patients or issues with informed consent or institutional review board oversight; and in 20, for violations not otherwise categorized. Examples of uncategorized violations include cases in which the investigators used experimental compounds in patients not enrolled in trials, delegated tasks to unauthorized personnel, or otherwise failed to supervise clinical investigations properly.
This investigation had found numerous studies for which the FDA determined there was significant evidence of fraudulent or otherwise problematic data. Such issues raise questions about the integrity of a clinical trial, and mention of these problems is missing from the relevant peer-reviewed literature. The FDA does not typically notify journals when a site participating in a published clinical trial receives an OAI inspection, nor does it generally make any announcement intended to alert the public about the research misconduct that it finds.
The scary thing about these findings, in my opinion, is that many trials were not able to be fully investigated in this study due to redacted information. Had their been better open access to the data contained in these trials, more evidence of fraud may have been uncovered. So next time you argue that pharmaceutical medicine is all evidence based, on sound science, remember articles like this one, to remind you that human beings AT ANY LEVEL are capable of falsifying data to mislead the public.