Suicidality Assessments in Clinical Trials

In September 2010 the FDA released its Draft Guidance on Suicidality: Prospective Assessment of Occurrence in Clinical Trials that presents the FDA’s current thinking on suicidality monitoring appropriate for clinical trials.

A primary goal of suicidality monitoring during drug trials is to determine if the drug under investigation increases suicidal tendencies or attempts. Such testing during clinical trials is currently not mandated and not implemented for most drugs being readied for market.

Suicidality Assessments in Clinical Trials

Monitoring suicidality is a recent development in clinical trials and the current debates point to the need to gain concurrence on a fully structured, procedurally reliable process for monitoring suicidality. The following methodological issues with clinical trials of antipsychotic drugs can be generalised to suicidality monitoring:

1. Representativeness of the population included in clinical trial. For example, are psychiatric patients included or excluded from the clinical trial? The general methodological question becomes is the study population representative of the population who will be prescribed the drug?
2. Lack of clearly defined and uniform rating instruments employed in clinical trials, especially those applicable to psychiatric drugs.
3. Incomplete reporting of adverse side effects. Currently adverse side effects that occur in less than 5 percent of the sample population are not reported. Suicidality may occur in only a small fraction of the overall population prescribed the drug and thus occur in a limited number of cases in clinical trials.

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FDA Draft Gudiance

The latest FDA guidance on suicidality measures in clinical trials focuses significant attention on uniform assessment of suicidal risk for all clinical trials for classes of drugs with known linkages to psychiatric side effects. The FDA recommends use of the rating scale already in use for antidepressant drugs, the Columbia Classification Algorithm for Suicide Assessment (C-CASA), which has become the standard for coding suicidality data. A companion instrument to the classification algorithm is the Columbia Suicide Severity Rating Scale (C-SSRS) assesses occurrences, types, and severity of suicidal ideation and behavior through a series of structured probing questions. While FDA guidance recommends use of C-CASA and C-SSRS, the FDA allows the use of alternative instruments if reviewers permit.

The FDA also recommends that suicidality assessments in clinical trials occur at baseline as well as at each patient visit. Assessments need to be performed for all clinic trial participants of at-risk drug classes, including those participants with no history of psychiatric illness.

Applied environment

One mechanism for administering the C-SSRS is as part of a face-to-face interview; however this method is not only time consuming on the part of staff, it has been shown that patients respond more openly about suicidality issues in the private setting of computer interaction. One such instrument, called the eC-SSRS, is a computerised self-assessment tool that presents the standardised, structured set of questions of the C-SSRS to the clinical trial participant. Based upon the given answers, the software presents the appropriate follow-up questions based upon a pre-determined branching tree structure.

In addition to saving time and eliciting more accurate answers, the eC-SSRS is available with voice-activated features usable via telephone calls which not only monitor patient’s suicidality status but also accurately record results and rate them without human bias.

Electronic methods like eC-SSRS provide a fully structured, procedurally reliable process for monitoring suicidality that complies with the latest FDA guidance.

References

[1] U.S. Department of Health and Human Services, Suicidality: Prospective Assessment of Occurrence in Clinical Trials, 2010. http://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/UCM225130.pdf

[2] Bell GS & Sander JW. Suicide and epilepsy. Curr Opin Neurol. 2009 Apr;22(2):174-8 http://www.ncbi.nlm.nih.gov/pubmed/19532042

[3] Hitti M. FDA Checks Into Singulair Suicide Risk, March 27, 2008. http://www.webmd.com/asthma/news/20080327/fda-checks-into-singulair-suicide-risk

[4] Hitti M. FDA: No Suicide Risk From Singulair, January 13, 2009. http://www.webmd.com/asthma/news/20090113/fda-no-suicide-risk-from-singulair

[5] Gibb G. FDA Employs Full Tool Box to Monitor Chantix, October 21, 2010. http://www.lawyersandsettlements.com/articles/15232/chantix-suicide-side-effects-51.html

[6] Leucht S, Heres S, Hamaan J, Kane, J. Methodological Issues in Current Antipsychotic Drug Trials. Schizophr Bull (2008) 34 (2): 275-285. http://schizophreniabulletin.oxfordjournals.org/content/34/2/275.full

[7] Posner K, Oquendo MA, Gould M, Stanley B, Davies M. Columbia Classification Algorithm of Suicide Assessment (C-CASA): classification of suicidal events in the FDA's pediatric suicidal risk analysis of antidepressants. Am J Psychiatry. 2007 Jul;164(7):1035-43. http://www.ncbi.nlm.nih.gov/pubmed/17606655

[8] Columbia University Medical Center. Columbia Suicide Severity Rating Scale (C-SSRS). http://www.cssrs.columbia.edu/

[9] Federico M. Compliance: Suicidality Monitoring, November 1, 2010. http://appliedclinicaltrialsonline.findpharma.com/appliedclinicaltrials/CRO%2FSponsor/Compliance-Suicidality-Monitoring/ArticleStandard/Article/detail/693544?contextCategoryId=44912