Did Drug Companies Try to Hide Suicidality?
Like the tobacco companies knowing nicotine was addictive yet hiding it from the public, did the antidepressant manufacturers know that their data implied increased suicide risk -- and try to conceal that from the FDA? (or even from themselves? UPDATE 4/9/04 -- the Los Angeles Times obtained a document that suggests the FDA may indeed have tried to keep it from themselves: here's that story)
At least one company coded "possibly suicide-related events", as they are now called by the FDA, under the term "emotional lability", lumped there with other non-suicidal symptoms and behaviors. Listen to Dr. Laughren of the FDA commenting on how they decided to request more specific data from manufacturers -- i.e. not just accepting the data as the company had filed it. Notice how the response they got led to the ban on antidepressants for kids in Britain:
(From the FDA 2004 hearing transcript: http://www.fda.gov/ohrms/dockets/ac/cder04.html#psychopharmacologicdrugs )
now let me talk a little bit about
how the signal came onto our radar screen.
reviewed over the past three to
pediatric supplements for 8 drugs, and we looked at
the safety and efficacy data for these drugs.
In the course of putting together a report
for FDA, companies code their adverse event data,
and they do this in their own ways. We
them how to code the data, they choose their own
dictionaries and they set about coding the data
before they send it in.
This applied to any events suggestive of
suicidality, as well as any other adverse events.
We reviewed those supplements over this period of
three to four years, and suicidality did not emerge
as a matter of concern based on those reviews.
However, the Paxil review did raise a
1 question about data
management, in that events
2 suggestive of
suicidality were coded under the
3 general preferred
term "emotional lability."
This struck the reviewer as rather odd,
5 and so in responding
to GSK, we asked them to
6 separate out the
verbatim terms suggestive of
7 suicidality under a
term specific to suicidality.
That request to GlaxoSmithKline resulted
in additional work and ultimately resulted in a
report on paroxetine and pediatric suicidality.
That report went first to the MHRA -- that is FDA's
counterpart in the
FDA in May of last year.
That report indeed suggested an increased
risk of suicidality associated with paroxetine use
in particular in one of the three studies done in
Wyeth wrote its own Warning letter to doctors, before the recent FDA Warning requirement, based on their own data, without further guidance by the FDA. Yet, as pointed out in testimony in the 2/2004 hearing, this company had those data for years. Did they just coincidentally get around to reviewing their own data just as the FDA began its review? Here is a link to the table with those data.
UNDER CONSTRUCTION BELOW
Here are some other notes from the transcript review:
Conclusion by Dr. MOSHOLDER
In conclusion, for the study of this issue
of pediatric suicidal behavior associated with
antidepressant treatment, the available
pharmacoepidemiological data and postmarketing
surveillance data is of limited utility, and
randomized, controlled trial data should be
16 superior to these sources.
Fundamental limitations in understanding these data:
reviews efficacy data in kids (pg 285, line 20)
Notes the FDA standard of two positive studies; fluoxetine has that, none of the rest do; but the latter is subject to interpretation, which he explains. On the whole it's pretty suggestive these work for some kids, and that none is clearly better than the others.
(291, line 1) He explains that these data are not "proof of the lack of benefit".
Note the very interesting twist (289, starts line 5) where he explains that in the TCA days, the studies a company would have to submit where not set up to require "positive" studies -- and thus implies that the current set-up, so requiring, may warp the data in favor of efficacy. Very damning of the process, if you read him close.