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FDA mandates
suicide studies in clinical
drug trials
(April 2008
Issue)
By Phyllis Hanlon
On April 20, 1999, Eric Harris and Dylan Klebold killed 12 students
and a teacher and wounded 26 others before turning their weapons
on themselves in the notorious Columbine shootings. In Minnesota,
Jeff Weise murdered his grandparents, shot seven students and a
teacher and wounded seven at the Red Lake Indian Reservation before
killing himself in March 2005. Last December, Robert Hawkins committed
suicide in an Omaha mall after first fatally shooting eight people
and wounding five others.
In all of these instances, the perpetrators were reported to have
been taking some type of prescription antianxiety or antidepressant
medication. Aware of the risk of drug-related suicide, The Food
and Drug Administration (FDA) has taken a closer look at how stringent
data collection in ongoing and future clinical trials can be a proactive
means of achieving better safety monitoring.
Sandy Walsh, FDA Office of Public Affairs, indicates that there
is no new regulation or policy change in which FDA is requiring
drug makers to assess psychiatric side effects of all new drugs.
Rather, each new clinical trial will be evaluated individually.
"On a case-by-case basis, FDA may ask sponsors to either prospectively
collect and assess such information or retrospectively ask sponsors
to further analyze adverse event data. These determinations are
based on factors such as the class of the drug, what may be known
from other members of the class, findings from animal studies or
signals of imbalances in psychiatric adverse events reported in
controlled clinical trials," she says. "This type of data collection
and analysis is not new, rather FDA has been looking at this for
some time for certain types of drugs."
According to Walsh, the type of data collection tool most often
used, but not necessarily required by FDA, is the C-SSRS (Columbia
Suicide-Severity Rating Scale), a set of prompts and questions to
help an interviewer get more complete information on events suggestive
of suicidality. "Presumably the information gained from these interviews
would then be classified, at the data analysis stage, into the appropriate
bins, using the C-CASA (Columbia Classification Algorithm of Suicide
Assessment)," she says.
Kelly L. Posner, Ph.D., principal investigator for the FDA/Columbia
Classification Study at Columbia University, notes that using the
C-SSRS will enable researchers to better identify and assess a
patient's suicidal ideation and behavior, resulting in more positive
outcomes. "If we can't properly identify suicidality risk, we cannot
manage, treat or understand it," she says. "Suicide is a major public
health issue. Identification is the first step, whether it's research
on drug safety or clinical management."
The C-SSRS standardizes terminology and articulates suicidality
assessment in a straightforward manner, according to Posner. "Now
clinical trials, clinical practice and surveillance can all start
to speak the same language," she says. Previously, there was no
consistent methodology for defining key terms.
This prospective tool has been translated into 80 different languages
and has been used in clinical trials for six years. Additionally,
the C-SSRS has played an integral role in large multi-site industry
trials, both in this country and around the globe, in community
clinics and practices and in a range of therapeutic areas, says
Posner.
While antipsychotic and other types of psychiatric agents have
garnered the most attention, other classes of prescription drugs
have been known to cause adverse effects. Walsh says, "We've been
aware of psychiatric side effects of non-psychiatric drugs for a
very long time, e.g., certain antihypertensives can cause depression,
steroids have obvious psychiatric symptoms, certain antibiotics,
Accutane, etc. What's a little different now is that we are focusing
more on trying to detect these effects earlier, in clinical trials,
rather than waiting for a post-marketing signal and also trying
to improve the post-marketing methods of detecting signals."
Benjamin A. Toll, Ph.D., assistant professor, Yale School of Medicine,
Department of Psychiatry, is using the C-SSRS for a clinical trial
involving Chantix (veranocline), an anti-smoking drug connected
through case reports with possible suicides. "There is no strong
evidence, only case studies," he says. "We give the scale at every
session as part of best practice," he says. "We are not predicting
that they are suicidal, but if they are, we will attend to it. I'm
pleased to say we've not found anyone suicidal."
Toll sees value to both the individual and to society from using
the C-SSRS. He says, "Some people maybe reticent to reveal thoughts
about committing suicide. They might feel awkward or strange telling
a clinician. By specifically asking the questions, we're giving
them the opening to say they're having these thoughts. It starts
the dialogue."
The community-at-large benefits from this type of screening when
its citizens are appropriately and adequately treated, Toll says.
He adds that ethical reasons serve as a compelling factor for administering
the questionnaire.
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