A case study of statistics in the regulatory process: the FD&C Red No. 40 experiments.
Unexpected findings in a mouse study in which the safety of FD&C No. 40 (Red 40) was examined led to additional experimentation and to new statistical analyses and models. The possibility of acceleration of tumors raised questions about an operational definition of acceleration and of appropriate statistical methods for assessing acceleration, especially in the face of data dredging. The evaluation of Red 40 was further complicated by cage and litter effects and the multigenerational design. In this report the investigations of these studies are reviewed and are used to illustrate how new scientific work can emerge through the regulatory process. A number of issues in animal experimentation that need to be examind are indicated.
D000818:Animals; D000830:Animals, Laboratory; D001391:Azo Compounds / Q000266:history / Q000633:toxicity*; D002273:Carcinogens; D004032:Diet; D004353:Drug Evaluation, Preclinical; D005260:Female; D005503:Food Additives / Q000266:history / Q000633:toxicity*; D008297:Male; D051379:Mice; D008954:Models, Biological; D009369:Neoplasms / Q000139:chemically induced*; D051381:Rats; D012107:Research Design; D013223:Statistics as Topic; D013997:Time Factors; D014481:United States; D014486:United States Food and Drug Administration
D001391:Azo Compounds; D002273:Carcinogens; D005503:Food Additives; C005915:Allura Red AC Dye