Rampant Underreported Research Misconduct

It is not surprising to hear clinical trials sometimes struggle with data integrity and quality issues.  Such undertakings can be logistically challenging, and certainly any substantial scope of effort leads to the occasional cutting of corners.

However, there are also millions (or billions) of dollars in revenue, along with multiple professional reputations, at stake.  This creates fertile territory for the more nefarious sort of data corruption.  In some instances, the Food and Drug Administration performs site monitoring as evaluation for misconduct.  And, as this study indicates, the FDA sometimes discovers serious issues – issues almost always swept under the rug.

Using a variety of methods, including Freedom of Information Act requests, FDA.gov site exploration, and other FDA published warnings, these authors compiled a list of 421 serious irregularities identified by FDA audit.  However, heavily redacted language in many of the documents discovered precluded linkage to clinical trials – resulting in only 57 published trials that could be linked to serious violations.  These 57 trials resulted in 78 identifiable publications – only 3 of which mentioned or addressed the issues raised by the FDA.  Those three specifically noted data excluded due to protocol errors, data falsification, or inappropriate monitoring.  The remaining 75 publications did not.

A couple examples:

• 8 of 16 FDA inspections of sites for RECORD 4, a rivaroxaban trial for DVT prophylaxis, identified unblinding, falsification of records, and randomization improprieties.  The associated study publications do not mention such issues.
• A clinical site in China falsified data regarding apixiban in ARISTOTLE.  Excluding such data from the final study report would eliminate any apparent mortality benefit, but publications continue reporting mortality benefit analyses based on the entire data set.

The lack of transparency and apparent action regarding what is certainly just the tip of the iceberg is staggering.  How is it our own drug safety organization fails to protect patients on such a scale?  Is it any wonder so few clinical trial results hold up on re-examination?

“Research Misconduct Identified by the US Food and Drug Administration”
http://www.ncbi.nlm.nih.gov/pubmed/25664866