Active approach to assessing suicidality in trials needed; FDA
Meta-analyses of antidepressant and antiepileptic trials have contributed to increased focus on treatment-emergent suicidality. In response the US Food and Drug Administration (FDA) has issued draft guidance which calls for a more proactive approach to suicidality monitoring.
To ensure suicidal patients are properly identified and treated the FDA recommends prospectively assessing suicidality in clinical trials. This has the added benefit of improving analysis by ensuring the collection of more timely and complete data on suicidality.
Investigators could use the Columbia Suicide Severity Rating Scale (C-SSRS) to assess patients. This is a series of questions about possible suicidal thinking and behaviours which should be asked at baseline and at each patient visit.
Columbia Classification Algorithm for Suicide Assessment (C-CASA) is used to categorise information from C-SSRS. C-CASA categories include: completed suicide; suicide attempt; preparatory actions toward imminent suicidal behaviour; and suicidal ideation.
The FDA considers these categories to represent suicidality. C-CASA also has categories for: self-injurious behaviour intent unknown; fatal event, not enough information; self-injurious behaviour without suicidal intent; other; and nonfatal event, not enough information.
Determining trials for suicidality assessment
Suicidality assessments should be performed in clinical trials involving any drugs for psychiatric indications, as well as for all antiepileptic treatments and other neurological therapeutics with central nervous system (CNS) activity.
The FDA also recommends assessing suicidality when trialling certain non-psychiatric drugs with suicide concerns. These include: isotretinoin and other tretinoins; beta blockers, especially those entering the brain; reserpine; drugs for smoking cessation; and weight loss treatments.
Phase I studies involving healthy volunteers and single-dose trials must assessed for suicidality when criteria listed above are met. Microdose trials and studies involving populations with cognitive impairment, such as Alzheimer’s, can be excluded from suicidality assessment.
The FDA considered recommending conducting suicidality assessments as part of all trials but decided against this approach. Further experience may lead to a revision of this recommendation and the FDA is seeking comments and this and other issues raised by the guidance.
