Safety pharmacology investigations on the nervous system: An industry survey

Simon Authier, Joseph Arezzo, Marcus S. Delatte, Mary Jeanne Kallman, Carrie Markgraf, Dominique Paquette, Michael K. Pugsley, Sian Ratcliffe, William S. Redfern, Joanne Stevens, Jean Pierre Valentin, Hugo M. Vargas, Michael J. Curtis

Research output: Contribution to journalArticle

26 Scopus citations

Abstract

The Safety Pharmacology Society (SPS) conducted an industry survey in 2015 to identify industry practices as they relate to central, peripheral and autonomic nervous system (‘CNS’) drug safety testing. One hundred fifty-eight (158) participants from Asia (16%), Europe (20%) and North America (56%) responded to the survey. 52% of participants were from pharmaceutical companies (> 1000 employees). Oncology (67%) and neurology/psychiatry (66%) were the most frequent target indications pursued by companies followed by inflammation (48%), cardiovascular (43%), metabolic (39%), infectious (37%), orphan (32%) and respiratory (29%) diseases. Seizures (67% of participants), gait abnormalities (67%), tremors (65%), emesis (56%), sedation (52%) and salivation (47%) were the most commonly encountered CNS issues in pre-clinical drug development while headache (65%), emesis/nausea (60%), fatigue (51%) and dizziness (49%) were the most frequent issues encountered in Phase I clinical trials. 54% of respondents reported that a standard battery of tests applied to screen drug candidates was the approach most commonly used to address non-clinical CNS safety testing. A minority (14% of all participants) reported using electroencephalography (EEG) screening prior to animal inclusion on toxicology studies. The most frequent group size was n = 8 for functional observation battery (FOB), polysomnography and seizure liability studies. FOB evaluations were conducted in a dedicated room (78%) by blinded personnel (66%) with control for circadian cycle (55%) effects (e.g., dosing at a standardized time; balancing time of day across treatment groups). The rat was reported as the most common species used for seizure liability, nerve conduction and drug-abuse liability testing.

Original languageEnglish (US)
Pages (from-to)37-46
Number of pages10
JournalJournal of Pharmacological and Toxicological Methods
Volume81
DOIs
StatePublished - Sep 1 2016

Keywords

  • Abuse
  • EEG
  • Neurological functional observation battery
  • Safety pharmacology
  • Seizure
  • Sleep

ASJC Scopus subject areas

  • Toxicology
  • Pharmacology

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    Authier, S., Arezzo, J., Delatte, M. S., Kallman, M. J., Markgraf, C., Paquette, D., Pugsley, M. K., Ratcliffe, S., Redfern, W. S., Stevens, J., Valentin, J. P., Vargas, H. M., & Curtis, M. J. (2016). Safety pharmacology investigations on the nervous system: An industry survey. Journal of Pharmacological and Toxicological Methods, 81, 37-46. https://doi.org/10.1016/j.vascn.2016.06.001