Pradaxa and Drug Safety: Product Liability Played a Role

This week’s post is about the problem of product liability in pharmaceutical policy, an issue that I have not discussed since my first posts on this blog in February.  Boerhinger-Ingelheim’s drug Pradaxa (dabigatran) is a “thrombin inhibitor,” an anticoagulant drug used to prevent strokes and embolisms in patients with atrial fibrillation or other conditions that put them at high risk for stroke. One of the principal selling points of Pradaxa and other direct thrombin inhibitors is that their recommended use does not monitoring patient’s blood levels of the drug, unlike the much older drug Coumadin (warfarin) which is used for the same purpose but has a different mechanism of action and requires individual dosing and monitoring. Pradaxa has been the subject of very interesting news this past week, initiated by an article by Deborah Cohen, M.D. in the British Medical Journal (BMJ) entitled: Concerns over data in key dabigatran trial.  Accompanying the article was a feature editorial with the even more attention-grabbing title: Dabigatran: how the drug company withheld important analyses

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I have been interested in the question of liability in connection with Pradaxa for some time.  In mid-November of 2012 I assigned my Torts II students to write a memorandum evaluating the potential liability of BI in product liability lawsuits for injuries resulting from Pradaxa. At the time I thought the issue an interesting one that was not too difficult, because on November 2, 2012, the FDA had approved several changes to the label of Pradaxa and also issued a “Safety Alert” noting the unusual number of adverse incident reports concerning patients taking Pradaxa who had suffered serious bleeds.  I thought the question interesting because the new warnings raised the issue of whether the prior label had adequately informed doctors and the patients of the drug’s risks.  I thought the question was not too difficult for my students because I provided them with material about the FDA’s Sentinel Initiative and the way that it provided an important new tool for tracking adverse effects of a drug.  The “answer” to my assignment was that BI’s liability for the greater risk of bleeding than was contained in the earlier label for the drug depended on whether or not BI had been making a reasonable effort to track the incidence of bleeding, using the Sentinel database and BI’s own safety monitoring tools.  If the increased risk of bleeding should not have been detected earlier and the labeling change made sooner, then BI might be liable.  If reasonable diligence would not have shown the problem sooner, than BI ought not to be liable.

It turns out that there was more to the issue of Pradaxa’s safety than just the adequacy of BI’s post-marketing surveillance program.  As Deborah Cohen’s article points out, the entire premise that Pradaxa can be safely used without monitoring individual patient’s responses is now being questioned.  The BMJ article by Dr. Cohen was the subject of news stories throughout the media, from The Wall Street Journal to Medscape as well as virtually every publication focused on the pharmaceutical industry. While Dr. Cohen’s article raises a number of concerns about both the quality of the data as well as the analysis of the data that supported Pradaxa’s approval and use, the part of Dr. Cohen’s article that gained the most attention was this sentence:

Documents released during US litigation and those obtained through freedom of information show how Boehringer Ingelheim, the makers of dabigatran, failed to share with regulators information on how monitoring plasma levels of the drug and subsequent dose adjustment could reduce risk of major bleeds.

In other words, fewer people would die or be injured by Pradaxa if patients taking the drug were monitored to determine the rate at which they metabolized the drug. Even worse, according to Cohen, BI had concealed the value of monitoring from the FDA and European regulators.  Since Pradaxa’s biggest selling point is that it can be used without monitoring, this is a very serious charge-- accusing BI of putting its profits ahead of patient safety.  My purpose in this post is not to review or critique the strength of Dr. Cohen’s analysis or to add to the very long list of comments on the underlying issue of whether or not Pradaxa is safe and effective, better or worse than competing drugs, or would be significantly safer with monitoring.  Instead, I will focus on another part of the above quote from Cohen: “Documents released during US litigation….” In May of this year, BI paid $650 million to settle most of the nearly 4000 lawsuits brought by persons claiming death or serious injuries alleging that they suffered injuries as a result of a failure of BI to warn them of the nature and full extent of the drug’s risks.

Whether or not Dr. Cohen is right in asserting that safe use of Pradaxa requires individual patient monitoring is beyond the scope of this post. However, this an important debate and it would not be taking place if it were not for the much-disparaged plaintiffs’ lawyers who took these cases and sought this evidence and for the federal district judge who ordered the evidence be made available to the public.  Product liability is not the most efficient means of either promoting drug safety or even compensating people who suffer adverse consequences from pharmaceuticals; however, it may play an important role in motivating drug companies (and other manufacturers of potentially dangerous products) to do the right thing.  General Motors’ executives hid the dangers of an ignition switch for a number of years and the company is now suffering consequences in the marketplace and in product liability costs.  Boehringer Ingelheim has already paid $650 million for claims arising from Pradaxa and faces significant fallout for both decreased sales of the drug and BI’s corporate reputation.  One would certainly hope that when drug company executives are faced with the question of whether or not to release the results of studies that may damage the sales of one of their drugs their concern would be about the validity of the results, not the profitability of the product.  Unfortunately, that is not always the case.  Sometimes we may need the potential impact of product liability on a company’s reputation and bottom line to refocus mangagement’s attention.