in the first place?…

Posted on Wednesday 19 March 2014

Recently, I veered from my usual topic of psychiatric medications and their producers to a similar issue with a drug from my past life, Pradaxa®, and anticoagulant used to prevent clots forming in cases of atrial fibrillation – an irregular heart rhythm [how many examples?…, foot-in-mouth disease…]. Such clots can cause thrombo-embolic strokes. Now, Roy Poses of Healthcare Renewal presents us with the mechanisms of deceit which he calls prestidigitation, sleight of hand, or legerdemain – the techniques magicians use to divert attention away from the actual tricks behind their magic.
Healthcare Renewal
by Roy Poses
03/18/2014

Presto Chango

According to Bloomberg, here is how Boehringer-Ingelheim responded to the question from the FDA about the rate of fatal bleeding.
    That effort produced two separate analyses by the company, according to the unsealed court documents. One, looking only at people whose primary cause of death was bleeding, found 5.8 of 10,000 patients died per year. The other, which included anyone who had a major bleeding event and died for any reason, found a rate of 19.5 fatal events per 10,000 patients per year, the documents show.

    The report sent to the FDA, though, contained only the analysis indicating the death rate from the earlier research was much higher than the numbers seen after approval, according to the court filings. Potentially, such a finding could head off any after-market action by the FDA because the data showed the drug was safer after it was approved and widely used.
So, to recapitulate, Boehringer-Ingelheim used results from the RE-LY trial to persuade the FDA that its new drug was safe and effective. However, the company did not include, at least in the results reported publicly, any measure of fatal bleeding in patients given the drug. It now appears that the rate of major bleeding in patients who subsequently died was high, perhaps high enough to have raised questions about the safety of the drug prior to approval, had it been revealed.

However, after the drug had been approved, when the question was about rates of severe bleeding after the drug had been marketed, the company furnished an analysis of data from the clinical trial that now showed a very high bleeding rate. That was the major misdirection, the sleight of hand.. It would make the rate of fatal bleeding in the post-marketing surveillance data appear low.

But apparently this data also kept the eyes of the FDA focused on the question of bleeding in the post-marketing period.  Did no one in the FDA notice that while this high rate of bad bleeding in the trial made the post-marketing surveillance look good, it also raised questions about whether the drug should have been thought to have been safe enough to be approved in the first place?
Pretty slick stuff. Lowball the Adverse Event for approval, highball the same study for comparison with the postmarketing Adverse Event rates. A double duty use of a single datum that you might enjoy in a movie like The Sting or Butch Cassidy and the Sundance Kid, but unfortunately, this isn’t a movie about beloved con men of the Old West. it’s about hiding a lethal consequence from a drug people pay for to take to improve their chances of a longer, better life. That can’t have just happened. It had to be thought about – both in the approval process and in the after-the-fact Adverse Effects study. They had to know that the drug was dangerous and decided to actively suppress detection or investigation of that danger. Computers don’t do prestidigitation or sleight of hand. Those are things people do with the numbers computers generate. And where was the FDA in all of this?
But apparently this data also kept the eyes of the FDA focused on the question of bleeding in the post-marketing period.  Did no one in the FDA notice that while this high rate of bad bleeding in the trial made the post-marketing surveillance look good, it also raised questions about whether the drug should have been thought to have been safe enough to be approved in the first place?   

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