Clinical and Statistical Assessment of Suicidal Ideation and Behavior in Pharmaceutical Trials

Abstract

In the past two decades, the potential association between the risk of suicidal ideation and behavior and the clinical use of pharmaceutical products has been debated among industry, regulators, and academia. A better understanding of the possible effects-favorable, unfavorable, or neutral-of pharmaceuticals on the risk of suicidal ideation and behavior may be required, especially for trials typically designed for other primary objectives. Here, a cross-industry statistical team provides recommendations that address the assessment, statistical analysis, interpretation, and utility of suicide-related data in pharmaceutical clinical trials. These recommendations are to evaluate suicidal ideation, suicidal behavior, and the two combined as end points; utilize standard scales to collect data prospectively; and analyze the data using several statistical methods. A more accurate assessment of the potential association between the use of pharmaceutical products and risk of suicide-related events will contribute to estimating the benefit/risk ratio and result in safer medicines for patients.

Elevated C-reactive protein levels in schizophrenia inpatients is associated with aggressive behavior

“…As inflammation is associated with affective symptomatology [23], which often underlies suicidal thoughts and actions, it is plausible that the exclusion of patients with mood disorder in our cohort (major depression, bipolar or schizoaffective disorders) may account for the lack of association between elevated CRP and suicidality. In addition, the fact that suicidal thoughts and acts were not specifically evaluated by designated suicide assessment tools, due to the retrospective nature of the study, may further limit the capacity of the current study to elucidate such association, due to the complexity of defining suicidal thoughts or actions as a distinct behavioral phenotype [24].…”

Depression and suicidality in psoriasis: review of the literature including the cytokine theory of depression

“…62 A similar tool, the Columbia suicide severity rating scale (C-SSRS), is used to identify and quantify severity of SIB. 61,64 The C-SSRS employs a questionnaire to measure the frequency and severity of SIB and is recommended by the USFDA for the measurement of SIB in clinical trials. 57 Phase 3 clinical trials of brodalumab, a therapeutic agent being investigated for the treatment of psoriasis, have used the C-SSRS to measure SIB.…”

“…The C‐CASA is a reliable tool for retrospective classification of suicidal adverse events in clinical trials of antidepressants . A similar tool, the Columbia suicide severity rating scale (C‐SSRS), is used to identify and quantify severity of SIB . The C‐SSRS employs a questionnaire to measure the frequency and severity of SIB and is recommended by the USFDA for the measurement of SIB in clinical trials .…”

Effects of vilazodone on suicidal ideation and behavior in adults with major depressive disorder or generalized anxiety disorder

“…These instruments are generally more sensitive than reports of suicide-related treatment-emergent adverse events (TEAEs). Although such TEAE data are useful, patient reporting of TEAEs is not as comprehensive or as consistent as C-SSRS monitoring ( Gassmann-Mayer et al , 2011 ). The C-SSRS is an 11-category rating system that incorporates both individual patient responses and external sources (e.g.…”