Opinion ID: 510618
Heading Depth: 3
Heading Rank: 4

Heading: Single-dose study design

Text: 30 Petitioners contend that the reduction in weight gain and increased mortality observed at the end of the nursing phase of the CCMA study in animals fed the two percent dose fails to justify the conclusion that two percent is the MTD for the entire study. Petitioners' objection focuses on the design of the study. The weight reduction and pup mortality observations, they argue, demonstrate only that two percent is the best maximum dose for the in utero phase, but have no bearing on whether two percent is the appropriate MTD for the adult phase. Petitioners advert to the Red Book statement that as a result of maternal and fetal toxicity it is often necessary to use lower doses during the in utero phase of the study in order to produce sufficient offspring for the post-weaning phase. Red Book at 121, J.A. at 87. There is confusing evidence in the record concerning the superiority and reliability of single-dose studies as compared to those in which the dose is elevated at mid-point. We do not deny that a more direct explanation of why the FDA accepted the single-dose design for the CCMA study would have been desirable. However, the short answer to petitioners' objection is that independent observations in adult rats, already discussed, validate two percent as the MTD for the adult phase. Thus, record evidence justifies a conclusion that raising the highest dose above two percent after the in utero phase would not have resulted in an acceptable study.