Background Information on the Suicidality Classification Project

The field of psychiatry has been challenged by a lack of conceptual clarity about suicidal behavior, and a corresponding lack of well-defined terminology. This is reflected in the lack of systematic or standardized language to define suicidal behavior in the original 25 clinical trials of selective serotonin reuptake inhibitors (SSRIs) and other antidepressant drug products in pediatric patients with various psychiatric diagnoses. This lack of standardized terminology for suicidal acts makes it difficult to interpret the meaning of reported adverse events (AEs) that occurred in those studies.

There may be adverse events that were inappropriately classified as suicidal, while other suicidal AEs may have been missed. Illustrative problematic examples include a case classified as a suicide attempt, in which a child slapped herself in the head and a case in which a child stabbed himself in the neck with a pencil, which was classified as an accidental injury.

To avoid unfounded conclusions and misinterpretation, a common set of guidelines must be applied. In order to say with greater confidence whether a behavior is suicidal, the data need to be examined consistently across trials, using research-supported definitions that are both valid (relevant features have been shown to be associated with definition) and reliable (clinicians are able to use these definitions in similar ways). Standardized terminology will be agreed upon before interpreting adverse events.

To address this problem, an independent panel of internationally-recognized experts in suicide assessment and adolescent suicide research will be convened to classify data from the pediatric depression trials. This distinguished panel is independent, in that no member has had any involvement in the drug treatment trials in question.

National and international panel members will include but are not limited to:

• David Brent, M.D., University of Pittsburgh, an expert in suicide risk factors and assessment and management of adolescent suicidal behavior (with a particular expertise in psychotherapeutic interventions);
• Anthony Spirito, Ph.D., ABPP, Brown University, who studies adolescent suicide attempters, with a particular focus on psychotherapy intervention;
• Peter Marzuk, M.D., Weill Medical College of Cornell University, who studies assessment/classification, epidemiology, and variables associated to suicide (aggression and violence, drug-abuse);
• Patrick O’Carroll, M.D., M.P.H., who is the Regional Health Administrator for U.S. Department of Health and Human Services; previously with the Center for Disease Control and Prevention. He led all of CDC’s epidemiologic research and prevention efforts related to attempted and completed suicide, particularly focusing on suicide classification issues;
• Greg Brown, Ph.D., University of Pennsylvania, who has studied the assessment of suicidal behavior and the development of practice guidelines for management of adolescent and adult suicidal patients in primary care and behavioral health settings, as well as in psychotherapy interventions for individuals at high risk for suicide;
• Annette Beautrais, Ph.D., who conducts the Canterbury Suicide Project, Department of Psychological Medicine, Christchurch School of Medicine, New Zealand. She has systematically collected data on suicide identification, monitoring, and epidemiology of secular trends in completed suicide in adolescents.
• Cheryl King, Ph.D., ABPP, University of Michigan, an expert on adolescent suicidal behavior, who is conducting research on psychosocial interventions for suicidal adolescents. She is past President of the American Association of Suicidology.

Kelly Posner, Ph.D., Maria A. Oquendo, M.D., Madelyn Gould, Ph.D., M.P.H., and other research scientists at Columbia University with expertise in suicide classification, assessment techniques, and genetic and treatment research will be responsible for convening the expert panel, as well as for the design, implementation, and oversight of the classification methodology and its application to the FDA data. The project will involve reviewing clinical descriptions of events and rating whether a particular event can be classified as suicidal. The procedures to accomplish this are based on the Columbia team’s experience with training of others in suicide assessment, development of measures and manuals to aid assessment of suicide, and use of suicide event consensus conference procedures.

Research-based definitions, established before the data are reviewed, will be systematically applied to case descriptions. The documents that will be circulated for review will include information that was deemed to be relevant pursuant to requests from the FDA. All narratives will have been de-identified of information on the patients, the pharmaceutical company, and the drug being studied, prior to the panel's receiving them and before expert review. Panel members will initially participate in a training session and pre-reliability study, to ensure that application of research-supported definitions will be conducted in a consistent way. The expert panel will then systematically review over 400 case descriptions from the 25 pediatric trials, including events that were originally described as possibly suicidal, all events coded as accidental injuries, and all serious adverse events. The review of the additional events that were not originally indicated as possibly suicidal renders the process more meaningful by allowing for a more objective review (i.e., reviewers, in addition to not knowing what treatment the subject received, also will not know the initial classification of any cases). Furthermore, the review of the additional cases will allow for the possibility of the identification of missed suicidal cases, since as mentioned previously, there may be some cases among the accidental injuries that were not classified appropriately. The approximately 400 cases will be randomly assigned to panel members in such a manner that each case will be independently reviewed by multiple raters. If there is non-agreement on any particular event, the case will be reviewed in a consensus procedure. If consensus still cannot be reached, the case will be classified as "indeterminate."

The panel’s task will be to rate whether a described event belongs in a particular behavioral classification. Classifications will include: suicidal events (suicide attempts, aborted attempts [for example, a child/adolescent changed his/her mind before starting the potentially self-injurious act], and interrupted attempts [for example, someone stopped the child/adolescent before potential injury began], and suicidal ideation-related events); non-suicidal events (self-injury or mutilation without suicidal intent, events attributable to other psychiatric symptoms, medical or accidental injuries); and indeterminate events (non-consensus or unable to classify due to limited data). Of note, the panel will also provide confidence assessments for each classification, indicating how certain they feel about a particular classification, based on the information provided.

Classification determinations will then be provided to the FDA. Neither the expert panel nor Columbia University will be responsible for interpretation or analysis of the panel’s ratings of events. The suicidality classification project is solely responsible for the methodology that will produce expert classification ratings.

Guidelines that will foster better ascertainment of suicide-related information and adverse event determination are warranted. The Suicidality Classification Project will inform researchers from Columbia in the development of such guidelines, enabling appropriate classification and identification of suicidality-related events and behavior. This may lead to a greater consistency of categorization of what does and does not constitute a suicidal event and improve suicide identification and surveillance.

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Date created: March 22, 2004

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