Suicide rating scale can be valuable assessment tool in drug studies
FDA requests use of Columbia scale in some trials
The controversy of the past few years over possible suicidality associated with various drugs pointed out the importance of tracking suicidal thoughts or behavior in subjects involved in clinical trials.
But until recently, it was hard to find resources that could be used to accomplish that objective. Thanks to a project at Columbia University in New York City that was prompted by a request from the FDA, it's now possible not only to look back at suicidality in adverse events from previous clinical trials, but also to move forward with suicide assessments in current and future drug trials.
Kelly Posner, PhD, who is on faculty at Columbia and is principal investigator for the FDA/Columbia Suicide Classification Study, says that in the past, it has been difficult to gauge the suicidality associated with drugs because there was a lack of clarity in defining suicidal behavior and no common terminology to describe it.
"This cuts across all clinical and research settings," she says. "The same events get called 12 different things and it results in not being able to make sense of what you need to, either for the clinician, a study, or epidemiological data.
"If you can't properly identify suicidal ideation or behavior, you can't understand, manage, or treat it."
When the FDA first was faced with the challenge of looking at potential suicidality associated with antidepressants, the agency went to Posner's team, which had been running a treatment trial for adolescent suicide attempters for the National Institute of Mental Health.
The FDA asked Posner's group to develop a system of analyzing the adverse events from previous antidepressant clinical trials to try to make sense of them.
Posner says the adverse event reports from the trials were all they had to go on, as patients weren't questioned routinely about suicidal thoughts or behavior.
Even when an event occurred, "They weren't trained to ask the right questions to figure out if something is suicidal or not."
The result could be a true suicide attempt that wasn't identified as such or the opposite an event that was inappropriately classified as a suicide attempt.
For example, one patient's overdose of the study medication, originally described as accidental, was later reclassified as intentional. On the other hand, a patient who slapped herself in the face was initially labeled a suicide attempt, and later reclassified.
Because of this inconsistency and inaccuracy in identifying suicidal behavior, Posner says it's difficult to know the true risk of the drugs being studied.
"For example, we assume there is a risk with antidepressants, but in fact, because the safety data relied on these adverse events, we actually don't know that, because association doesn't mean causality," she says.
It could be possible that patients on the active medication suffered side effects that caused them to spend more time with researchers, and reveal suicidal thoughts or actions, as opposed to the control group, which may have had similar thoughts or actions but not the same opportunities to discuss them.
Posner's team created the Columbia Classification Algorithm for Suicide Assessment (C-CASA), which helped categorize the adverse events as suicidal, indeterminate, or non-suicidal. Under this system, they found more total suicidal events than previously had been classified, but fewer actual suicide attempts.
Since the development of C-CASA in 2001, the FDA has asked pharmaceutical companies in "a handful of cases" to analyze their data using the tool, says Crystal Rice, spokeswoman for the agency.
"We've been asking for this information on a case-by-case basis, when other drugs in the same class have been linked to suicidality or when signals in clinical trial data suggest this might be a risk," Rice says. "We are not requiring this information broadly as a part of drug applications."
Although the C-CASA retrospective analysis of past drug trials can provide useful information, Posner says a prospective system one that systematically asks patients about suicidal ideation or actions during a drug trial is the ideal.
To address that, the Columbia group developed the Columbia Suicide Severity Rating Scale (C-SSRS), a brief questionnaire that researchers can administer to all the patients in a drug trial at every visit.
"We're doing it consistently across the drug and placebo [arms]," she says. "And it also fixes all the other problems it gives definitions, it gives the questions to ask to figure out what to call something, it deals with all the problems we've seen in the retrospective trials and data."
The C-SSRS asks about suicidal ideation, and creates a range from a passive wish to die through creating a plan and having intent. It asks about indicators that are highly predictive of a completed suicide duration of suicidal thoughts, their frequency, and controllability.
There are questions about specific behaviors, and in the case of actual suicide attempts, about the lethality of the method used.
"It gives you everything that you'd want to track in any setting," Posner says. "It was developed to track adverse events and suicidality throughout any treatment trial or in any setting."
The scale originally was developed for use with adolescents and has been used across the age span. It has been translated into 80 languages and is being used around the world, Posner says.
Posner says the questionnaire itself can be administered in as little as five minutes, which makes it usable even in a busy treatment setting.
"It is increasingly used in primary care, non-psychiatry populations, and the feasibility is excellent," she says. "Obviously, people think of burden when you're doing it so often, especially in non-psychiatrist offices. But it just hasn't been the experience."
Rice says that similar to the C-CASA requests it has made of drug makers, the FDA now may ask sponsors of certain drugs to use the C-SSRS to collect suicidality data during current trials.
"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.
She says the FDA requests are made on a case-by-case basis, calling the amount of requests a "small subset of applications" the agency has reviewed. Rice disputes some recent media reports that suggested there were new FDA policies requiring the use of the C-SSRS in drug trials.
Even absent a request from the FDA, Posner says researchers are increasingly using the scale when conducting trials of new drugs, even non-psychotropic drugs, recognizing the importance of tracking this problem using a common language and methodology.
She says a study authored by Madelyn Gould, PhD, MPH, who helped develop the C-SSRS, has shown that the introduction of questions about suicidality does not increase risk to subjects.
"Asking these questions does not cause patients to be suicidal or cause them to be distressed," Posner says. "That's clinical lore and the data tell us something else. What we do know is it's critically important to ask about it, for the patient's safety and our understanding of data."
Posner says wider use of the Columbia Suicide Severity Rating Scale actually could debunk false ideas about risk, because it would eliminate the ascertainment bias that comes with only speaking to certain subjects about suicide.
In addition, it creates data that can be compared from study to study.
"I think what's exciting about this is that we're all going to be speaking the same language," she says.
The controversy of the past few years over possible suicidality associated with various drugs pointed out the importance of tracking suicidal thoughts or behavior in subjects involved in clinical trials.You have reached your article limit for the month. Subscribe now to access this article plus other member-only content.
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