Misconduct Delayed Drug Approval

FDA endorsement of a new blood-thinning drug was held back for almost a year because the agency discovered misconduct at clinical trial sites in China.

Dan Cossins
Jul 10, 2013

WIKIMEDIA, TOM VARCOUS Food and Drug Administration (FDA) approval for the blood-thinning drug Eliquis was delayed for 9 months due to errors and misconduct at sites in China where clinical trials were performed, reported Bloomberg. Documents published by the FDA reveal that during trials overseen by Bristol-Myers Squibb (BMS), which developed the drug in partnership with Pfizer, some patients were given the wrong drug, records were badly kept and secretly manipulated to cover up good-practice violations, and “serious adverse reactions” went unreported.

The news raises questions about the reliability of clinical trials carried out in China, which has become a hotspot for such research because of the huge pool of potential subjects and the low costs, which can be as little as half of those in the U.S., according to the Tufts Center for the Study of Drug Development.

Thomas Marciniak, an FDA medical team leader who wasn’t...

Eliquis was developed as a safer alternative to warfarin, an anticoagulant commonly used to prevent blood clots. Starting in 2006, final-stage trials were performed on 18,000 patients across more than 1,000 sites in 40 countries, with much of the work carried out by contract research organizations. Twenty-six of those sites were in China, including the Shanghai 9th People’s Hospital, where the FDA uncovered a range of problems, including the manipulation of records. “The records were altered in order to cover-up GCP [good clinical practice] violations which had occurred at the site,” wrote the FDA in its report. BMS fired several employees involved in changing the data.

At a meeting held last February at the FDA’s campus in Silver Spring, Maryland, agency officials told BMS and Pfizer executives that the mistakes represent a “pattern of inadequate oversight,” adding that it was “uncertain whether it was reasonable to assume that the problems in trial conduct identified by the review team were all or even most of the significant problems.” The FDA officials also raised the possibility that the problems were more widespread, pointing out that one BMS employee who ordered data alterations worked at 18 other trial sites in China.  

The FDA eventually approved Eliquis last December, but did not release details about the issues they’d uncovered until now. The agency is “comfortable with the results” of the trial, Sandy Walsh, an FDA spokeswoman, told Bloomberg.