Establishing performance characteristics for positive control article selection in drug self-administration studies

摘要

The selection of a controlled substance (CS) for use as the positive control article in a nonclinical drug abuse liability (DAL) assessment study should be contemplated carefully and with full understanding of the stated intent of the study design. Any CS that can maintain day-to-day stable baseline responding of voluntary intravenous intakes in animals may be selected under the current guidelines. Schedule I - IV CNS stimulants, depressants, and sedative/hypnotics can serve as maintenance drugs in these protocols, but not all of these compounds will provide comparatively efficient, robust, and stable daily intakes. Each Sponsor is directed to select a positive control article and training dose that will provide the most balanced, predictive, and scientifically-sound comparison consistent with the mechanism of action or therapeutic target of the test article. The SA study design is not a "one-size-fits-all" assay. This is a discussion of the critical design factors to be considered in selecting the most appropriate positive control article to use for a SA study.