title: The nonclinical fertility study design for pharmaceuticals.
abstract: Assessment of potential developmental and reproductive toxicity of human pharmaceuticals is currently guided by the ICH S5(R2) document, "Detection of Toxicity to Reproduction for Medicinal Products and Toxicity to Male Fertility." Studies that assess a candidate drug's effect on fertility are generally conducted in rats. The evolution of, and ultimate harmonization of, fertility study designs are reviewed, and specific elements of an acceptable design, as well as the recommendations for presentation of data, are described in detail. Additionally, the timing of nonclinical fertility studies in relation to clinical studies that enroll men and women of reproductive potential is reviewed. Possible strategies for combining fertility assessment with other study designs are also presented. This article provides testing laboratories, sponsors, and regulatory agencies with a comparison of current methods and designs, with the aim of providing a common understanding of the critical design features.
authors.affiliation: GlaxoSmithKline R&D, King of Prussia, Pennsylvania 19406-0939, USA. steven.2.lerman@gsk.com
authors.forename: Steven A
authors.initials: SA
authors.lastname: Lerman
authors.forename: Kok Wah
authors.initials: KW
authors.lastname: Hew
authors.forename: Jane
authors.initials: J
authors.lastname: Stewart
authors.forename: Donald G
authors.initials: DG
authors.lastname: Stump
authors.forename: L David
authors.initials: LD
authors.lastname: Wise
mesh_terms: D000818:Animals; D064420:Drug-Related Side Effects and Adverse Reactions; D047108:Embryonic Development / Q000187:drug effects; D005260:Female; D005298:Fertility / Q000187:drug effects*; D007390:International Agencies; D007391:International Cooperation; D008297:Male; D023421:Models, Animal; D051381:Rats; D012107:Research Design; D018570:Risk Assessment; D013997:Time Factors; D018675:Toxicity Tests / Q000379:methods*