·  Legal News, Analysis, & Commentary


POGO Says FDA’s Pradaxa Review was “Lax” and “Permissive”

— October 16, 2015

An independent watchdog group, the Project on Government Oversight (POGO), found that the FDA’s approval of anti-coagulant drug Pradaxa was flawed. The POGO report details many poor decisions and conflicts of interest on the FDA’s part as it gave Boehringer, Pradaxa’s maker, several accommodations.

Watchdog group, Project on Government Oversight (POGO), recently issued an 81-page report to the FDA regarding the agency’s approval of anti-coagulant drug, Pradaxa. In essence, POGO says FDA’s Pradaxa review was “lax” and “permissive” and full of questionable decisions.

The POGO investigation was conducted via patient and researcher interviews and the review of thousands of pages of public records. Upon completion, the group determined that the regulatory and approval process for Pradaxa does “not inspire confidence in the regulation of prescription drugs.” POGO wants to see the FDA put a greater emphasis on drug safety with “higher standards” for clinical trials.


“… In the FDA’s oversight of Pradaxa and in the factors it was willing to overlook when reviewing the manufacturer’s clinical trial, the agency has appeared permissive. The FDA’s own record appears to contain good reasons for the agency to have taken a different approach” with Pradaxa.

According to POGO’s study, the FDA made poor decisions to “accommodate” Boehringer Ingelheim, Pradaxa’s maker. These decisions include looser standards for Boehringer’s company-sponsored clinical trial and inadequate warnings about the potential risks to patients.

Pradaxa was meant to be a wonder drug, the new generation of anticoagulant medication. Free of dietary restrictions and blood test requirements, Pradaxa was set to replace Warfarin as the treatment for stroke prevention and blood clots in those with atrial fibrillation, a heart-rhythm condition.

All of this would have been great if not for the increased risk of potentially fatal bleeding events in Pradaxa patients. In fact, Boehringer settled roughly 4,000 suits last year over the failure to warn of the risks. These settlements cost the company $650M. Even worse is the disclosure of company documents in those suits.

The documents clearly showed that Boehringher staff wanted some of the company’s internal research revised or suppressed. Why? They felt that the results of their own research would lead patients to decide they needed the same level of monitoring as they did with Warfarin. Of course, this would have been a huge hit to one of the major selling points of the drug and, subsequently, to Boehringer’s bottom line.

An FDA spokesperson, Sandy Walsh, said the agency stands by Pradaxa as it provides “an important health benefit when used as directed. Health-care professionals who prescribe Pradaxa are asked to carefully follow the dosing recommendations in the drug label, especially for patients with severe renal impairment to reduce the risk of bleeding.”

POGO begs to differ. The watchdog group began studying the FDA’s review in 2013 and made some surprising (and frightening) discoveries:

  • The FDA approved Pradaxa with full knowledge that there was no antidote to counteract the drug’s effect in the event of a bleeding event. The company is working on an antidote now, however.
  • In response to reports of fatal bleeding events, the FDA still defended Pradaxa’s safety. Outside experts found that the science supporting the agency’s statements was “deeply flawed.”
  • Despite the fact that Pradaxa may cause fatal bleeding events, that information is found only in fine print on the package insert rather than in a “black box” warning. Warfarin has a black box-framed warning about “major or fatal bleeding” events.
  • Pradaxa got FDA approval based on one clinical trial. A medical officer in the FDA’s Division of Cardiovascular and Renal Products said the lack of a second, confirming, trial “adds a measure of uncertainty.”
  • The sole trial was “unblinded,” meaning that the researchers knew which patients were taking Pradaxa. A key FDA reviewer said they researchers handled those patients differently, taking them off of Pradaxa at the first sign of trouble. This made the drug appear safer.
  • When the FDA inspectors found that the doctors running the trial had mismanaged their part of it, the FDA didn’t restrict their participation in other clinical trials. Instead, the doctors received warnings and were asked to tell the FDA how they would avoid such “mistakes” (some serious) in the future.

Perhaps the worst discovery was that some members of the FDA advisory committee that endorsed Pradaxa by a 9 – 0 vote had serious conflicts of interest. Two members were found, via financial disclosures, to have made “substantial financial relationships with Boehringer.”

Clearly, the FDA fell down on the job in regards to Pradaxa. Sadly, that’s cost many innocent patients their lives. While POGO hopes for more stringent standards, I’m somewhat doubtful we’ll see any in the future. As President Obama’s nomination to head the FDA, Dr. Robert Califf, awaits Senate approval, controversy continues to brew over Califf’s extensive industry ties.

It very well may be a case of hiring a fox to guard the chicken coop. Only time will tell.


FDA was ‘lax’ and kowtowed to drugmaker in review of controversial blood thinner, watchdog says

Join the conversation!