FDA Accused of Lax Oversight in Pradaxa Approval Process

A new report from the Project on Government Oversight (POGO) includes serious criticisms of the FDA and the process through which it approved Pradaxa, Boehringer Ingelheim’s widely used, yet highly controversial anticoagulant drug.

The comprehensive review of Pradaxa’s path to the American market accuses the regulatory agency of being “lax, “permissive” and inappropriately deferential to the drug manufacturer.

Report casts doubt on regulatory process

The lengthy report included numerous interviews with researchers, patients and also delved into reams of public records which ultimately led to the conclusion that the FDA’s approval process, particularly in this instance, leaves lots of room for improvement. The authors of the critique suggest that the FDA’s failings call into serious question the trustworthiness of prescription drug regulation in this country.

Key facts about Pradaxa

A new-generation blood-thinning drug, Pradaxa received approval from the FDA in 2010. Touted as a breakthrough intended to take the place of traditional anticoagulant warfarin, the drug works to prevent blood clots and strokes in patients diagnosed with atrial fibrillation. Among the benefits of Pradaxa was the fact that patients using it would not be subjected to the dietary restrictions and routine blood testing required by warfarin.

However, just last year Boehringer Ingelheim agreed to settle roughly 4,000 Pradaxa lawsuits for a total of $650 million, following allegations that the drug giant did not adequately warn patients about the medication’s potential to cause dangerous, even fatal bleeding events. As a result of the litigation, documents were made public which revealed that employees of the drug company sought to revise and conceal internal research findings about the drug which could harm its market appeal.

Troubling findings included in POGO critique

POGO’s review began in 2013 and yielded a series of very troubling concerns related to the FDA’s attempt to balance the interest in introducing promising medications to the general public quickly with the need to ensure their safety.

Among the most glaring issues revealed in the report include:

• The agency granted approval to the drug despite the knowledge that unlike warfarin, Pradaxa had no known antidote which could stop serious bleeding events which were known to occur in some patients.

• In the face of increasing reports of life-threatening Pradaxa side effects involving internal bleeding, the FDA continued to publicly defend the medication, even though the scientific reasoning for that report was questionable.

• While Pradaxa was known to pose bleeding risks, the FDA never required its packaging to include a so-called “black box” warning about that fact. Warfarin, which has been in use for a much longer period of time, does bear such a warning.

• Pradaxa was approved by the FDA on the basis of just one clinical trial. Without a second trial providing confirmation of the findings of the first, a serious degree of uncertainty about the drug’s safety has persisted.

• FDA approval came as a result of an “unblinded” trial in which researchers were aware of which subjects were given Pradaxa and subsequently handled them in such a way as to give a greater impression of the drug’s safety.

• Researchers who were discovered to have mishandled portions of the trial were never banned by the FDA from further participation, but were instead given reprimands and opportunities to explain how they would prevent recurrences of what were sometimes very serious errors.

• The agency acquiesced to Boehringer’s desire to make specific advertising claims stating that Pradaxa was a superior anticoagulant drug to warfarin, something which certain insiders believed would lead successful warfarin patients to believe that they should switch drugs even though it was far from clear that benefits would result from such a choice.

• Individuals on the FDA’s advisory committee responsible for reviewing and recommending approval of the drug had notable ties to the drug making industry, with two of them having ultimately established significant financial connections to Pradaxa’s manufacturer.

Report urges funding increases

POGO’s report ended with a series of detailed recommendations designed to prevent the types of scenarios characterizing Pradaxa’s FDA approval. The authors of the review urge the agency to utilize its existing authority to address many of the issues revealed therein. However, POGO cautions that implementation of many such recommendations would be challenging unless Congress provides the FDA with funding increases in the near future.

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