Importance: Suicide is a public health crisis, and despite renewed efforts to confront this problem, suicide rates continue to rise in the US. While suicide prevention encompasses a broad array of strategies, treatment development is lagging. Within this realm, clinical trials are the criterion standard for evaluating safety and efficacy of new treatments.
Observations: Most clinical trials conducted among patients with mental illness have excluded patients at risk of suicide. Historical reasons for this include regulatory challenges, liability concerns, ethical questions, discomfort working directly with high-risk patients, and the belief that research is too risky for individuals at elevated risk for suicide.
Conclusions and relevance: Several considerations are provided for investigators in the design of trials targeting at-risk populations, including thoughtful selection of study outcome, use of time-to-event design and analysis (which may simultaneously satisfy ethical concerns and scientific aims), enrolling an enriched sample (eg, among patients recently discharged from the hospital), and provision of usual care in the comparator group. Caution should be exercised to avoid excessive or unreasonable safety requirements, which may lead participants to minimize self-report of suicidal ideation or to drop out of trials. Where possible, regulatory bodies (institutional review boards [IRBs] and data and safety monitoring boards) should consult with or include as members those with direct clinical experience with this high-risk population. An important ethical principle for IRB members and other regulators to consider is that suicide-related events are expected in this clinical population.