title: The role of adverse events and related safety data in the pre-market evaluation of drug abuse potential.
abstract: The scientific and regulatory assessment of abuse and dependence potential of drugs involves a multi-layered evaluation of its properties related to chemistry, formulation, pharmacology, animal behavior and clinical response. In addition to the primary laboratory-based assessment in experienced drug users, data are also reviewed from studies in healthy volunteers and in the patient population. Much of the emphasis in these latter studies is placed on adverse events that are reported by the subject or observed by the investigator. Unlike other aspects of abuse potential assessment, the evaluation of abuse- and dependence-related events has not been the subject of scholarly research. The present commentary presents recommendations for several areas that would benefit from a consensus review to result in greater standardization for the analysis and presentation of abuse- and dependence-related data from clinical trials. These include special investigator training, a system of weighted primary and secondary terms, adjudication of individual events, case report management, organization of integrated safety data, and protocols for drug accountability. Such an effort would aid in implementing the evolving efforts of health authorities to guide drug developers in the collection and presentation of data needed for the regulation of drugs with the potential for abuse and dependence.
authors.affiliation: Kendle Early Stage - Toronto, 720 King Street West, Toronto, Ontario M5V 2T3, Canada. rmansbach@fastmail.net
authors.forename: Robert S
authors.initials: RS
authors.lastname: Mansbach
authors.forename: Kerri A
authors.initials: KA
authors.lastname: Schoedel
authors.forename: Jeffrey P
authors.initials: JP
authors.lastname: Kittrelle
authors.forename: Edward M
authors.initials: EM
authors.lastname: Sellers
mesh_terms: D059019:Clinical Coding; D002986:Clinical Trials as Topic; D017277:Drug Approval; D062787:Drug Overdose; D064420:Drug-Related Side Effects and Adverse Reactions; D006801:Humans; D011569:Psychiatric Status Rating Scales; D013375:Substance Withdrawal Syndrome; D019966:Substance-Related Disorders