Pradaxa Lawsuits Raise Questions Over Clinical Trial Data Accuracy

A university and research center have found themselves brought into the Pradaxa litigation, with claims raised in some lawsuits alleging that inaccurate clinical trial data provided by the institutions helped the controversial blood thinner obtain approval in the U.S.  

At least two Pradaxa lawsuits name McMaster University and Hamilton Health Sciences as co-defendants, along with the drug’s manufacturer, Boehringer Ingelheim. The Canadian institutions run the Population Health Research Institute (PHRI), which conducted the clinical trial for Pradaxa, known as RE-LY. 

According to a report by The Spectator, an Ontario paper, it is likely they will eventually be made co-defendants in thousands of product liability lawsuits filed by individuals throughout the United States who allege they suffered severe and sometimes fatal bleeding problems that were caused by side effects of Pradaxa.

Lawsuits allege that the findings of the researchers drew a picture of a drug that was far safer and more effective than warfarin, a blood thinner that had been the standard anticoagulation therapy for decades. However, even before the drug was approved, questions arose about the quality of the clinical trial data and whether the institute was more focused on providing accurate information or pleasing Boehringer Ingelheim.

Following thousands of adverse event reports, hundreds of deaths, and a growing number of complaints filed by those who were seriously injured or lost family members to the drug, the researchers now face even more questions and more suspicions regarding the clinical trial data.

Data Questioned Before Pradaxa Was Approved

Pradadxa (dabigatran) is a relatively new anticoagulant therapy that was approved by the FDA in October 2010. It was the first member of a new class of medications known as direct thrombin inhibitors, which are promoted as superior alternatives to warfarin for stroke prevention because they require less monitoring during treatment. However, Pradaxa and other direct thrombin inhibitors lack an effective reversal agent to allow doctors to stop the blood thinning effects of the medication if a problems develops.

Unlike warfarin, which can be quickly reversed with a dose of vitamin K and plasma, there is no available reversal agent for Pradaxa. While some studies have shown that the chances of bleeding may be about the same with the two drugs, evidence continues to emerge highlighting how Pradaxa bleeding problems may pose a more serious risk, since hemorrhages are typically harder to stop.

Before Pradaxa (dabigatran) was approved, FDA reviewers already had concerns about the data PHRI had submitted. The reviewers found transposed numbers, missing adverse events data, and more. An investigation of the institute uncovered more deficiencies, including failings in data management plans and found a number of procedures and manuals necessary for the trial had never been created or were created months or years after patients were enrolled.

“Although we recognized that there will be some errors in the data sets from large trials, the errors found by relatively unsophisticated means in clinically important data sets during preliminary review called into question the overall quality of those data sets and our confidence in them,” FDA reviewers wrote.

The federal drug regulatory agency turned down Pradaxa until the data was resubmitted eight months later. 

Pradaxa Problems

During the first full year the drug was on the market in the United States, the Institute for Safe Medication Practices (ISMP) found that adverse event reports involving Pradaxa problems surpassed all other medications regularly monitored by the group.

The FDA received at least 3,781 reports involving serious injuries associated with the use of Pradaxa during 2011, including 2,367 reports of hemorrhage and 542 patient deaths. This further increased concerns about the problems with the RE-Ly trial.

In a letter published in the Therapeutics Initiative in October 2011, researchers from the University of British Columbia warned that RE-LY was fundamentally flawed and said the drug should have never been approved.

The researchers found that key parts of the study, which was supposed to be a double-blind trial, meaning neither doctors nor patients knew what they were taking, was actually not properly blinded, which resulted in differential treatment of patients in some cases. They also noted that there was a strangely elevated number of cases of warfarin brain bleeding incidents recorded.

“Licensing of dabigatran 150 mg BID for atrial fibrillation is premature, pharmacologically irrational and unsafe for many patients,” they concluded. “An independent audit of RE-LY is needed to check for irregularities in conduct, sources of bias and the cause of the unusually high incidence of intracranial hemorrhage in the warfarin arm.”

The institute has defended its numbers and officials from McMasters and HHS have expressed confidence in the institute’s procedures and integrity.

Pradaxa Litigation

Boehringer Ingelheim now faces about 2,000 lawsuits over Pradaxa that have been filed throughout the United States, alleging that the drug maker failed to adequately research the medication or warn consumers and the medical community about the potential bleeding risks, as well as the lack of an antidote to allow doctors to stop the blood thinning effects of the medication.

Since August 2012, the federal Pradaxa litigation has been consolidated as part of an MDL, which is centralized before U.S. District Judge David R. Herndon in the Southern District of Illinois to reduce duplicative discovery, avoid conflicting rulings from different judges and to serve the convenience of the parties, witnesses and the courts. The company also faces Pradaxa lawsuits in state courts in Illinois, California and Connecticut.

As part of the coordinated management of the cases in the federal court system, Judge Herndon has scheduled a series of early trial dates in the Pradaxa MDL, known as bellwether cases. These trials are set to begin between August 2014 and February 2015, with the outcomes designed to help the parties gauge how juries are likely respond to certain evidence and testimony that may be repeated throughout a large number of cases.