title: Sensitivity of male reproductive endpoints in nonhuman primate toxicity studies: a statistical power analysis.
abstract: To determine the sensitivity of male reproductive toxicity endpoints in NHPs we performed a power analysis of routine and triggered endpoints using control data from sexually mature Asian and Mauritian NHPs. The power to detect a 50% change from control was 13-30% for male reproductive organ weights, ∼30% for testicular volume, 6-66% for seminal analyses and 10-78% for male hormones. Overall, male reproductive endpoints have poor power (less than 80%) to detect a 50% change from control with a group size of 3 monkeys. Confidently identifying adverse male reproductive effects with these endpoints would likely require specialized study designs with larger group sizes. Triggering of non-routine endpoints in cases where there is special concern for male reproductive toxicity is unlikely to increase sensitivity to detect adverse effects.
authors.affiliation: Worldwide Research & Development, Pfizer Inc, Groton, CT 06340, USA. Gregg.d.cappon@pfizer.com
authors.forename: G D
authors.initials: GD
authors.lastname: Cappon
authors.forename: D
authors.initials: D
authors.lastname: Potter
authors.forename: M E
authors.initials: ME
authors.lastname: Hurtt
authors.forename: G F
authors.initials: GF
authors.lastname: Weinbauer
authors.forename: C M
authors.initials: CM
authors.lastname: Luetjens
authors.forename: C J
authors.initials: CJ
authors.lastname: Bowman
mesh_terms: D000818:Animals; D003627:Data Interpretation, Statistical; D005640:Follicle Stimulating Hormone; D005837:Genitalia, Male; D007986:Luteinizing Hormone; D008252:Macaca fascicularis; D008297:Male; D009929:Organ Size; D012098:Reproduction; D013076:Sperm Count; D013081:Sperm Motility; D013739:Testosterone; D018675:Toxicity Tests / Q000706:statistics & numerical data*
chemical_list: D013739:Testosterone; D007986:Luteinizing Hormone; D005640:Follicle Stimulating Hormone
keywords: Inhibin B; Male reproductive toxicity; NHP; Power analysis; Seminal analysis; Sperm count; Sperm motility; Testosterone