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OBJECTIVE: To survey the current approaches of clinical trial sponsors in prospective suicidal ideation and behavior assessments and challenges encountered. DESIGN: An internet-based survey. SETTING: Inclusion of prospective assessments of suicidal ideation and behavior in industry-sponsored clinical studies were required following the release of the September 2010 United States Federal Drug Administration draft guidance. The International Society for CNS Clinical Trials and Methodology Suicidal Ideation and Behavior Assessment Workgroup conducted an online survey to understand industry practices and experiences in implementing suicidal ideation and behavior assessments in clinical trials. PARTICIPANTS: The survey was sent to 1,447 industry employees at 178 pharmaceutical companies. A total of 89 evaluable responses, representing 39 companies, were obtained. MEASUREMENTS: A 30-item internet survey was developed asking about potential challenges and issues in implementing prospective suicidal ideation and behavior assessments. RESULTS: Common factors in deciding whether to include suicidal ideation and behavior assessments in a clinical trial were psychiatric or neurologic drug product (95%); central nervous system activity (78%); disease (74%) and patient population (71%); and regulatory announcements and policies (74%). The most common challenges in implementing suicidal ideation and behavior assessments included cross-cultural differences in acceptance of SIB assessments (40%); obtaining adequate baseline history (36.8%); obtaining translations (35%); investigator/rater discomfort with asking about suicidal ideation and behavior (32%); and inadequate training of raters to administer suicidal ideation and behavior ratings (30%). CONCLUSION: Among sponsors surveyed, the implementation rate of suicidal ideation and behavior assessment in central nervous systems studies is very high. Most have used the Columbia-Suicide Severity Rating Scale. Challenges regarding standardization of retrospective assessment timeframes and differing approaches to summarizing and analyzing suicidal ideation and behavior-related study data were frequently reported. These results suggest that inconsistent reports of suicidal ideation and behavior within study datasets may occur and that integration of data across studies remains a concern.
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OBJECTIVE: To assess fall events in older depressed patients during treatment with duloxetine. METHOD: Post hoc analysis of solicited fall events collected at each study visit using a questionnaire during a 24-week, multicenter, randomized, placebo-controlled, double-blind, phase 4 trial (November 2006 to November 2009). Older outpatients (≥ 65 years) with major depressive disorder (DSM-IV criteria) were randomly assigned to duloxetine 60 mg/d (n = 249) or placebo (n = 121) for the 12-week acute phase, after which the duloxetine dose could be increased to 120 mg/d and nonresponding placebo patients could be switched to duloxetine 60 mg/d. Between-treatment differences in percentages of patients with fall events were compared by Fisher exact test. Exposure-adjusted incidence rates (EAIRs) of falls per patient-year were also estimated. RESULTS: In the acute phase, 17.3% of patients treated with duloxetine 60 mg versus 11.6% treated with placebo (P = .170) experienced a fall event. Over 24 weeks, the percentage of patients with a fall while taking duloxetine 60 mg versus placebo was 24.0% versus 15.7% (P = .078), and the percentage was significantly higher in patients taking duloxetine regardless of dose (25.3%) than with placebo (15.7%, P = .045). Between-treatment differences in EAIRs over 12 weeks (0.26; 95% CI, -0.20 to 0.72) and over 24 weeks (0.27; 95% CI, -0.10 to 0.65) were not significant. CONCLUSIONS: Direct assessment of fall events greatly increases the number of falls reported by patients. Although the EAIR of falls per patient-year associated with duloxetine was not significant in this trial, clinicians should remain vigilant about the possibility of falls in older patients with duloxetine or any antidepressant treatment. TRIAL REGISTRATION: ClinicalTrials.gov identifier NCT00406848.