title: Integrated risk assessment of suicidal ideation and behavior in drug development.
abstract: Treatment-related suicidal ideation and behavior (SIB) adverse events are under increasing public, legal and regulatory scrutiny. Prospective assessment of SIB is emerging as a challenging safety requirement by health authorities for the development of drugs but the underlying risk factors remain ill defined. To help with the understanding of risk factors that trigger a prospective assessment of SIB in clinical trials, we present an industry consensus framework for risk assessment and decision making of SIB during drug development. Application of this strategy is based on chemical and pharmacological similarities of compounds with clinical evidence of suicidal intent, target or indication classes associated with high incidence of SIB, in vitro neuropharmacological activity profile, in vivo ADME properties, patient population of the underlying indication and regulatory precedents.
authors.affiliation: Global Pharma Development Strategy, Novartis Pharmaceuticals, Switzerland.
authors.forename: Patrick Y
authors.initials: PY
authors.lastname: Muller
authors.affiliation: Head of Toxicology, Genentech, United States.
authors.forename: Donna
authors.initials: D
authors.lastname: Dambach
authors.affiliation: Discovery Toxicology, Bristol-Myers Squibb, United States.
authors.forename: Brian
authors.initials: B
authors.lastname: Gemzik
authors.affiliation: Preclinical Safety, Novartis Institutes for Biomedical Research, Switzerland.
authors.forename: Andreas
authors.initials: A
authors.lastname: Hartmann
authors.affiliation: Safety Pharmacology COE, Pfizer, United States.
authors.forename: Sian
authors.initials: S
authors.lastname: Ratcliffe
authors.affiliation: Preclinical Safety, Novartis Institutes for Biomedical Research, Switzerland.
authors.forename: Christian
authors.initials: C
authors.lastname: Trendelenburg
authors.affiliation: Preclinical Safety Profiling, Novartis Institutes for Biomedical Research, United States. Electronic address: laszlo.urban@novartis.com.
authors.forename: Laszlo
authors.initials: L
authors.lastname: Urban
mesh_terms: D000818:Animals; D002986:Clinical Trials as Topic; D003657:Decision Making; D015195:Drug Design; D064420:Drug-Related Side Effects and Adverse Reactions / Q000517:prevention & control; D006801:Humans; D018570:Risk Assessment / Q000379:methods; D012307:Risk Factors; D059020:Suicidal Ideation; D000092864:Suicide Prevention