Thanks to Dr. Roy Poses at Health Care Renewal:
--for calling attention to two articles in the New York Times by Katie Thomas:
Let me give some medical background and then review the
contents of Thomas’s articles, relay Dr. Poses’ take on the matter, and then
end with a reflection of my own.
For many years, the most commonly used oral anti-clotting
drug (commonly referred to mistakenly and misleadingly as “blood thinners”) has
been warfarin. Warfarin has a number of disadvantages. First, it has a very
narrow safety range—let blood levels get too low and the person is at risk for
forming potentially fatal clots; let them get too high and the person is at
risk for a potentially fatal bleeding episode. That leads to the second
disadvantage—that patients taking warfarin have to report regularly for blood
tests to measure the levels and to adjust the dose if needed. So if anyone
succeeds in developing a new-generation replacement for warfarin, but without
these problems, then it would qualify as a better mousetrap par excellence.
Recently, several firms have proclaimed the advent of the
better mousetrap; one version is Pradaxa (dabigatran) made by the German firm
Boehringer Ingelheim. Pradaxa has been marketed for preventing clots in one of
the most common conditions for which such drugs are prescribed, the irregular
heartbeat known as atrial fibrillation, and the company claims it is at least
as good as warfarin without requiring any inconvenient blood testing. Warfarin
works by blocking the step in the clotting process that’s controlled by Vitamin
K, so that if a patient taking warfarin starts bleeding dangerously, an
intravenous dose of Vitamin K will immediately reverse the drug’s effects.
Pradaxa and the other new drugs work at a different point in the clotting cycle
and there’s no available antidote if a patient bleeds—leading some experts to
advise that the drug is too dangerous to use for that reason alone. The FDA has
received reports of 1000 deaths attributed to Pradaxa (out of some 850,000
patients prescribed the drug, netting Boehringer the hefty revenues of $2B).
It’s patients suing the drug firm over Pradaxa-related harm
that led to the articles in the Times.
The judge ordered release of some documents related to the case that include
internal company e-mails about a research study coordinated by a company
scientist, Paul A. Reilly. Reilly’s study showed that a part of the safety
problem with Pradaxa was that some patients had too high a blood level and some
patients too low (sound familiar?). He concluded that a blood test that
measured drug levels could be helpful for at least some patients in avoiding
dangerous reactions. (Such a blood test is available now in Europe but not the
U.S.)
A draft of Reilly’s paper that included these findings
unleashed a storm of e-mails from other company scientists and officials. They
argued that publishing a paper with these conclusions would undermine the
company’s primary marketing point in favor of Pradaxa, the result of a
fine-tuned marketing effort going back a decade. Moreover, some feared that if
the paper were published, it would be that much harder to get the government
regulators to hold off demanding blood tests. The end result was that the paper
was published recently but with many of the offending details removed.
Boehringer Ingelheim insists that this was a simple matter
of scientific review and refinement. A draft was circulated, others chimed in
with appropriate criticisms, and in the end the final paper was suitably
modified to better present the actual facts. Nobody here but us scientists,
boss.
Other experts aren’t buying that, and Dr. Poses
appropriately asks how often such censoring of scientific findings in the name
of marketing occurs with no friendly judge to force the release of the secret
company documents.
One of the common complaints from pharmapologists is that
pharmascolds quite unfairly would have physicians distrust a scientific paper
merely because it’s sponsored by a drug company, when ideally, they should read
the paper carefully, review the methods, and believe the paper or not based
solely on its merits. Dr. Poses comes out with a powerful contrary statement: “I
strongly advocate that those who author authoritative systematic reviews,
meta-analyses, and clinical practice guidelines… assume the likelihood that all
commercially sponsored published clinical research has been manipulated…”
Now for my own comment—this sounds very much like a replay
of the case of the so-called atypical antipsychotics that we previously
discussed:
Recall there that a new class of drugs was introduced with
great fanfare and said to be far superior to the original class of drugs, and
only after years of use did it become clear in hindsight that the supposedly
new drugs were in fact hardly different at all from the old ones, except in the
eyes of the company marketers, who managed to bamboozle the entire medical
profession very neatly, much to the harm of patients.
Reilly PA, Lehr T, Haertter S, et al. The effect
of dabigatran plasma concentrations and patient characteristics on the
frequency of ischemic stroke and major bleeding in atrial fibrillation
patients: The REL-Y Trial (Randomized Evaluation of Long-term Anticoagulation
Therapy). Journal of the American College
of Cardiology 63:321-328, 2014.
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