Increased Deaths in Clinical Trials
Insight Magazine's interview with Dr. Thomas Laughren, team
leader for the neuropharmachological drug-products division of the FDA, shows
that FDA was caught off guard when Dr. Arif Khan independently analyzed FDA's
data revealing that the new psychotropic drugs--including antidepressants
(SSRIs) and antipsychotics-- substantially INCREASED the rate of suicide in
patients who participated in clinical trials testing the drugs' safety and
efficacy between 1985-2000.
(See: Clinical Psychiatry News
http://www2.eclinicalpsychiatrynews.com/scripts/om.dll/serve See also,
AHRP Infomail, Sept. 7, 2002)
Laughren couldn't explain why patients in clinical trials testing SSRI
antidepressants had a 68% increased rate of suicide compared to the general
population. Laughren's claim that the drugs approved for the treatment of
depression--which is thought to trigger suicide--were not approved for the
treatment to prevent suicide, is an example of Orlwelian"doublespeak."
Laughren also stated: "When you do a meta-analysis across a large number of
trials and you look at the other outcomes of suicide and attempted suicide,
you don't see any particular benefit from being assigned the drug compared to
placebo." But we were led to believe that the FDA approves drugs that are
beneficial compared to placebo!
Insight's investigative reporter poses a provocative question to the FDA:
"since the new SSRIs are approved to reduce risk among depressed patients,
does this data require a re-evaluation of the efficacy and safety of SSRIs?"
AHRP poses the following additional questions: Was the FDA aware of the
extraordinary high suicide rates in trials the agency monitored? Why did the
agency keep the information hidden from doctors and patients ?
http://www.insightmag.com/global_user_elements/printpage.cfm?storyid=285737
INSIGHT MAGAZINE
Medical Research To Die For
By: Kelly Patricia O Meara
09/30/02
--------------------------
Step right up, little lady, and get your serotonin selective reuptake
inhibitors (SSRIs) to treat anything and everything that ails the mind and
body — social phobias, eating disorders, insomnia, headaches and depression,
to name but a few. This "medication," guar-an-teed safe and efficacious by the
phantasmagoria of federal science, is prescribed to reduce the symptoms of
whatever ails you and to assure healthy and happier lives.
Ah, but caveat emptor, my friend! A recent study conducted by Arif Khan,
medical director of the Northwest Clinical Research Center in Bellevue, Wash.,
and adjunct professor of psychiatry at Duke University School of Medicine, has
revealed startling numbers of suicides committed and suicides attempted in the
clinical trials for the new SSRI antidepressants — numbers that for years had
been hidden from both prescribing physicians and the public.
Kahn has examined the official clinical drug-trial data for all SSRIs approved
by the Food and Drug Administration (FDA) between 1985 and 2000, in which
71,604 participants in the clinical trials were treated with antipsychotics,
all SSRIs and anticonvulsants. The rate of suicides in the general public is
11 in 100,000, which means an incidence rate for those participating in the
SSRI clinical trials of nearly 68 percent — that's 718 suicides for every
100,000. Kahn's research further revealed that nearly 4 percent of SSRI
drug-trial participants attempted suicide within the following year.
Because people with a history of suicide are excluded from drug trials, the
dramatically elevated drug-trial numbers revealed by Kahn raise important
questions. Given the large number of attempted and completed suicides among
drug-trial participants, why were these drugs approved by the FDA?
Furthermore, since the new SSRIs are approved to reduce risk among depressed
patients, does this data require a re-evaluation of the efficacy and safety of
SSRIs?
Asked what the FDA considers an acceptable number of deaths in clinical
trials, Thomas Laughren, team leader for the neuropharmachological
drug-products division of the FDA, tells Insight, "Your question is not
particularly pertinent because these trials are not designed to influence
suicide. If you look at any one individual trial it is very unlikely you will
find a suicide in the trial, and generally we don't."
You see, says Laughren, "It's only if you accumulate data across a large
number of trials that you even have enough data to look at. What you do see in
individual trials is that patients who get drugs improve more than patients
who get placebo. That's what we see. When you do a meta-analysis across a
large number of trials and you look at the other outcomes of suicide and
attempted suicide, you don't see any particular benefit from being assigned
the drug compared to placebo."
Which, of course, is the point. And Laughren further announced that "the drug
is not approved for the treatment of suicide. They are approved for the
treatment of depression. Dr. Khan's findings and our findings suggest that
these drugs that we're studying and approving for depression don't appear to
have a benefit on the outcome of suicide. That is not to say that they don't
have a benefit in treating depression."
The drugs don't have a "benefit" on the outcome of suicide, which they in fact
increase dramatically, but they do have a "benefit" for depression. How is
this possible when in fact the clinical trials for SSRIs show the suicide rate
increased by 68 percent?
"What this [increased suicide rate] would tell us," says Laughren, "is that
this is a serious condition, not a trivial condition. Depression is a serious
condition. If you look at individual trials there are so few suicides that you
wouldn't be able to make sense of it all. It's only after you look across
multiple development programs over a very long period of time that you have
enough events that you can get this kind of analysis."
So, does this mean that FDA should wait longer periods of time before
approving such drugs? "No," says Laughren, "because the data are very clearly
showing that these drugs benefit patients. What this tells us is that it is
very difficult to exclude patients that are suicidal. As hard as you try you
really are not able to predict who is suicidal and who is not. It [the trial
data] does not tell us that being in clinical trials puts you at risk of
suicide. It is not surprising to see a few suicides when you look at a fairly
large number of patients, many of whom are followed for months or years."
But the data show the suicide rate is elevated 68 percent when comparing SSRI
participants to those given placebo and to the general population. So the
question isn't whether being in a clinical trial puts a person at risk, but
whether a particular drug puts a participant in a clinical trial at risk.
Besides, what good does it do to be declared officially less depressed if it
means you are 68 percent more likely to kill yourself?
And Robert Whitaker, author of Mad in America: Bad Science, Bad Medicine and
the Enduring Mistreatment of the Mentally Ill, tells Insight that, "Clinical
trials are skewed against the placebo." Basically, explains Whitaker, "What
happens in these drug trials is that people who respond well are put into an
extension of the trial. The point is that the longer people are kept on
whatever arm they're in — either placebo or drug — you expect suicide rates to
drop over time. It's only the good responders through the six-week trials that
are put into the extension trials, and so it's biased against the placebo
because after six weeks no one is kept on to do extensions on placebo."
Whitaker says, "You shouldn't be seeing four to five times the suicide rate in
drug-treatment groups, especially when these drugs are supposed to prevent
this. It's terrible that the FDA approved drugs with these high suicide rates.
Naturally they do expect some suicides, but the question is whether there is
something the drug is doing that is increasing that rate, and here it looks
like it may be. A further question that has to be asked is why it has taken 15
years to find out about this data. Why are we learning about these increased
suicides in clinical trials 15 years after the drugs were approved?"
Reviewing the Kahn report on the clinical data, Whitaker says, "There are two
questions that need to be raised about the FDA review. First, is there an
elevated suicide risk beyond the background rates [number of depressed people
in the population] such that the drug should be seen as unsafe? And, second,
is there enough of a hint of suicide risk that it needs labeling? Is a public
warning needed with the SSRIs?"
He sees the Kahn revelations as "confirmation of what a lot of people have
been complaining about for many years. An analogy would be that you have some
disease, like cancer or heart disease, and you're going to see death in those
trials. The question with the new treatment is, 'Are you getting a lower,
higher or no difference in the number of deaths?' There is a key piece of
information missing from Dr. Khan's research and that is the background rate
for depression. Even so, we should be seeing in these trials a lower rate than
the background rate because people who are suicidal are excluded from
participating in the clinical trials — they are supposed to be testing these
drugs among safe populations. This data tells me something is very wrong."
Kahn did not respond to Insight's requests for an interview, but according to
Clinical Psychiatry News he reported to a meeting of the New Clinical Drug
Evaluation Unit of the National Institutes of Health that, "In the case of
trials for depression and anxiety disorders, suicide rates were in fact higher
among those who received the Investigational drugs than the placebo." In fact,
according to shocked experts, when projected the increase in both attempted
and completed suicides for those on the SSRIs is stunning. And the FDA knew
this when it approved these drugs.
Kelly Patricia O'Meara is an investigative reporter for Insight magazine.
--------------------------
Story Source: Insight on the News
Last Updated on
02/20/2005
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