title: Statistical design and monitoring of the Carotene and Retinol Efficacy Trial (CARET).
abstract: CARET is a chemoprevention trial of beta-carotene and vitamin A with lung cancer as the primary outcome. Participants at high risk for lung cancer are drawn from two populations: asbestos-exposed workers and heavy smokers. The intervention is a daily combination of 30 mg beta-carotene and 25,000 IU vitamin A as retinyl palmitate. Nearly 18,000 participants will be followed for a mean 6 years, yielding over 100,000 person-years of follow-up. We project that this sample size will have 80% power to detect a 23% decrease in the incidence of lung cancer cases. The purpose of this paper is to present the values of the key sample size parameters of CARET; our schemes for monitoring CARET for sample size adequacy, incidence of side effects, and efficacy of the study vitamins; an overview of the data collected; and plans for the primary, secondary, and ancillary analyses to be performed at the end of the trial. These approaches to the design, monitoring, and analysis of CARET are applicable for many other prevention trials.
authors.affiliation: Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, Washington 98104-2092.
authors.forename: M D
authors.initials: MD
authors.lastname: Thornquist
authors.forename: G S
authors.initials: GS
authors.lastname: Omenn
authors.forename: G E
authors.initials: GE
authors.lastname: Goodman
authors.forename: J E
authors.initials: JE
authors.lastname: Grizzle
authors.forename: L
authors.initials: L
authors.lastname: Rosenstock
authors.forename: S
authors.initials: S
authors.lastname: Barnhart
authors.forename: G L
authors.initials: GL
authors.lastname: Anderson
authors.forename: S
authors.initials: S
authors.lastname: Hammar
authors.forename: J
authors.initials: J
authors.lastname: Balmes
authors.forename: M
authors.initials: M
authors.lastname: Cherniack
mesh_terms: D000368:Aged; D016588:Anticarcinogenic Agents / Q000008:administration & dosage*; D001194:Asbestos / Q000009:adverse effects; D002338:Carotenoids / Q000008:administration & dosage*; D004224:Diterpenes; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000209:etiology / Q000517:prevention & control*; D008297:Male; D008875:Middle Aged; D012107:Research Design; D000084562:Retinyl Esters; D012307:Risk Factors; D012907:Smoking / Q000009:adverse effects; D014801:Vitamin A / Q000008:administration & dosage / Q000031:analogs & derivatives*; D019207:beta Carotene
chemical_list: D016588:Anticarcinogenic Agents; D004224:Diterpenes; D000084562:Retinyl Esters; D019207:beta Carotene; D014801:Vitamin A; D001194:Asbestos; C014794:retinol palmitate; D002338:Carotenoids