Suicide risk assessment in clinical trial drug development: part 1
Assessing the positive and negative effects of medications on suicide risk to protect study participants
Kelly Posner, Ph.D. – Professor of Psychiatry at Columbia University
John Greist, M.D. – Professor Emeritus of Psychiatry at the University of Wisconsin School of Medicine and Public Health and CEO at Healthcare Technology Systems, Inc
Accurately assessing suicidal ideation and behavior (SIB) is critical and often required by the Food and Drug Administration (FDA) in clinical trials designed to assess the safety and efficacy of new pharmaceuticals. Assessing SIB is of particular concern to the FDA for any compound that crosses the blood-brain barrier. The electronic Columbia-Suicide Severity Rating Scale (eC-SSRS), completed by patients during clinical trial visits combined with clinician follow-up as needed, provides an easy and comprehensive method for assessing potential effects of medications on suicide risk. Before discussing SIB assessment methods further, it is important to understand why regulators began issuing guidance around suicide risk assessment during drug development.
“Drug development trials must assess the positive and negative effects of medications on suicide risk to protect study participants taking medications entering broad general use after regulatory approval.”
Kelly Posner, PhD – Professor of Psychiatry at Columbia University
This first installment of a two-part series offers a cautionary tale illustrating the importance of Clinical Outcome Assessments (COAs) like the patient-reported eC-SSRS.
Before the present systematic assessment of SIB during drug development trials existed, a smoking cessation drug received FDA approval for use in 2006. It was a highly effective treatment and widely used almost immediately following approval. In 2009, following reports of serious neuropsychiatric events including but not limited to depression, suicidal ideation, suicide attempt and completed suicide, the FDA issued a “black box” warning regarding depression and suicide risk. As a result, use of the drug for smoking cessation decreased rapidly by approximately 50%.
FDA guidance on prospective assessment of suicidal ideation and behavior
In 2012, consistent with the experience with the smoking cessation drug, the FDA published Guidance for Industry Suicidal Ideation and Behavior: Prospective Assessment of Occurrence in Clinical Trials.2 The guidance described several issues and methods involved for assessing suicide risk during drug development:
“The purpose of this guidance is to assist sponsors in prospectively assessing the occurrence of treatment-emergent suicidal ideation and behavior in clinical trials of drug and biological products.
There are two reasons for prospectively assessing suicidal ideation and behavior in clinical trials. The first is to ensure that patients in clinical trials who are experiencing suicidal ideation and behavior are properly recognized, and adequately treated. The second is to ensure the collection of more timely (i.e., closer to the event) and more complete data on suicidal ideation and behavior than have been collected in the past so that increased suicidal ideation and behavior in individual trials and in pooled analyses are easier to detect. This is important whether or not a particular drug is known to be associated with treatment-emergent suicidal ideation and behavior.
Collection of such data will also provide scientifically sound evidence to evaluate concerns about a possible association with suicidal ideation and behavior for a drug that is based only on individual case reports.”
In response to the 2012 FDA guidance and other FDA requirements, the maker of the smoking cessation drug reported results of an 8000-patient post-marketing randomized controlled trial (RCT) in late 2016. The study findings resulted in the removal of the FDA boxed warning.1 But for the drug manufacturer, the seven-year recovery process came with enormous costs, including study expenses, lost sales, and perhaps most importantly, lost opportunities to benefit patients seeking to stop smoking.
In Part 2 of this series, Drs. Greist, Mundt and Posner will discuss how technologies, such as the patient-reported eC-SSRS, can help accurately evaluate suicidal ideation and behavior (SIB) in clinical trials, protecting both patients and drug development efforts of pharmaceutical companies. In the meantime, to learn more about how and when to monitor SIB effectively, contact our eCOA Science Team or visit Clario’s eC-SSRS webpage.
1 Anthenelli PM, Benowitz NL, West R, et al. Neuropsychiatric safety and efficacy of varenicline, bupropion, and nicotine patch in smokers with and without psychiatric disorders (EAGLES): a double-blind, randomized, placebo-controlled clinical trial. Lancet. 2016 Jun 18;387(10037):2507-20. doi: 10.1016/S0140-6736(16)30272-0. Epub 2016 Apr 22.
2 U.S. Department of Health and Human Services Food and Drug Administration Center for Drug Evaluation and Research. Guidance for Industry Suicidal Ideation and Behavior: Prospective Assessment of Occurrence in Clinical Trials. In: Products DoP, ed. Revision 1 ed. Rockville, MD: Food and Drug Administration; August 2012.