CPDD 78th Annual Scientific Meeting Program

Tuesday, June 14
XIII.
WORKSHOPS
Regulatory and methodological considerations in the evaluation of
drug dependence in the preclinical and clinical setting
Chairs: Beatrice Setnik and Michael Klein
Evaluating drug withdrawal effects is an integral component of dependence potential,
which informs the overall safety, appropriate dosing, and scheduling of a drug. The
methodological approaches to assess dependence continue to evolve and require
careful evaluation of both preclinical and clinical data. Physical dependence can
manifest from various drug classes including classes of drugs that are and are not
associated with substance use disorder (e.g. beta blockers, corticosteroids).
Preliminary approaches often include animal models to evaluate psychological
dependence and the physical manifestation of withdrawal type symptoms. Translation
of animal pharmacokinetics to human can be challenging and needs to be carefully
evaluated to determine the translatability of animal to human data. In the clinical
setting, evaluation of withdrawal requires characterization of a drug’s pharmacology to
determine what type of symptoms may manifest upon abrupt discontinuation. Study
populations must be carefully considered, particularly in patient populations that
cannot be safely withdrawn from study drug. Clinical trials must determine what
population, duration of maintenance and endpoints are relevant for a given drug.
Commonly adverse events and drug-specific withdrawal scales are included to evaluate
withdrawal symptoms, however other pharmacodynamics measures may also be
considered. The administration of endpoints and safety monitoring requires also
practical considerations in the context of larger patient trials, where confined stays
may not be possible following abrupt discontinuation. This workshop will address the
regulatory and methodological considerations that are rapidly evolving in this active
area of research and will cover case examples of studies examining drug withdrawal
and dependence.