Boehringer Admits Pradaxa Bleeding Deaths Higher than Revealed to FDA

Pradaxa’s manufacturer failed to inform the FDA that Pradaxa bleeding deaths were higher after the drug’s approval than in the study the company submitted to obtain agency authorization, according to a recent Bloomberg article.

After the FDA approved Pradaxa, drug maker Boehringer Ingleheim gave the agency data concerning the number of bleeding deaths suffered by Pradaxa users.  The company’s analysis concluded that death rates were lower than in the study the company had submitted to win initial FDA approval.

But Boehringer concealed another analysis of the same data, which found over three times as many Pradaxa bleeding deaths.

Pradaxa bleeding deaths

The FDA approved Pradaxa in October 2010 based on a single clinical trial overseen by Canadian researchers.  Charges have recently surfaced that the researchers concealed serious side effects in an effort to win favor with Boehringer and streamline the FDA’s approval.

Pradaxa patients began reporting life-threatening bleeding complications almost immediately.  According to the not-for-profit Institute for Safe Medication Practices, such bleeding episodes comprised the highest number of serious adverse health events reported directly to the FDA in both 2011 and 2012. Some 18% of bleeding reports ended in patient deaths.

FDA records reveal that Pradaxa bleeding events numbered 2,367 in 2011, while 542 patients died. The numbers increased in 2012, when the FDA received reports of 589 deaths and 3,292 serious complications, including uncontrolled bleeding.

The FDA acknowledges that these figures involve “substantial underreporting of adverse events,” and that many of the reports were incomplete.  As a result, in December 2013 the agency announced it would conduct “active surveillance” of Pradaxa patient records.  Instead of waiting for doctors to report bleeding injuries and deaths, the FDA will actively monitor records of all Pradaxa patients at 17 facilities, which treat nearly 100 million patients overall.

Pradaxa lawsuits over fatal bleeding events

Serious Pradaxa bleeding incidents and deaths have led to multiple product liability lawsuits against Boehringer in state courts in California, Connecticut, Delaware, and Illinois. Patients and families charge that Boehringer misrepresented Pradaxa’s risks and failed to warn of its side effects.

Pradaxa lawsuits were also filed in at least 11 federal courts.  In August 2012 those cases were consolidated for pretrial proceedings in so-called Multi-District Litigation (MDL).  U.S. District Judge David R. Herndon is handling the matter in federal court in East St. Louis, Illinois.  Over 2,300 Pradaxa lawsuits were pending under MDL as of March 2014.

Documents recently unsealed in the MDL show that the FDA asked Boehringer to determine a death rate from Pradaxa use by comparing the fatal bleeding reports received by the FDA to the number of patients using the drug.  As Bloomberg reported, Boehringer advised the agency that 6.1 of every 10,000 patients who used the drug after approval died from uncontrolled Pradaxa bleeding.   Given the FDA’s acknowledgement that bleeding events are significantly underreported to the agency, the validity of this figure is unclear.

The FDA also asked Boehringer to reanalyze results from Pradaxa’s pre-approval Canadian clinical trial.  The company produced two analyses of those results.  The first analysis, which examined patients whose primary cause of death was reported as bleeding, concluded that 5.8 of 10,000 patients died each year.

The other assessment included patients who suffered a major bleeding event and died for any reason.  Deaths in this group totalled 19.5 of every 10,000 patients per year.

Boehringer failed to inform the FDA that it had conducted the second analysis, and did not reveal that over three times as many deaths were attributed to Pradaxa bleeding using that analysis.  A Boehringer executive was unable to explain why the company concealed its second assessment.

On March 5, Judge Herndon ordered the first Pradaxa bellwether trial to begin in September 2014.

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