In the May 2, 1996 issue of The New England Journal of Medicine, the results of two large-scale randomized trials which included beta carotene were published: the Physicians' Health Study (PHS) and the Beta Carotene and Retinol Efficacy Trial (CARET). In the PHS, conducted among 22,071 US male physicians, after an average of 12 years of supplementation with beta carotene or placebo, there were no differences between the groups in the rates of malignant neoplasms, cancer mortality, cardiovascular mortality, or mortality from all causes. In the CARET study, 18,314 men and women at high risk of lung cancer, due to smoking or asbestos exposure, were assigned to a combination of beta carotene and retinol. This trial was terminated early by its Data Monitoring Board primarily because of an inability to demonstrate a benefit, but also because of observed possible increased risks of lung cancer, cardiovascular mortality, and total mortality consistent with the results of the Alpha-Tocopherol/Beta Carotene Cancer Prevention Study (ATBC). In a press conference convened by the National Cancer Institute (NCI) on January 17, 1996, NCI Director Dr. Richard Klausner emphasized the critical importance of continued follow-up of the trial cohorts. Given the unexpected results of ATBC and CARET, and the finding of no effect of beta carotene in the PHS, continued surveillance of all these trial cohorts is crucial to ensure complete documentation of the long-term health effects of beta carotene supplementation. To help achieve this goal, we have established the Antioxidant Trialists' Collaborative Group which will conduct a systematic meta-analysis of the post-publication results of continued follow-up in all completed trials, to fully assess the effects of beta carotene supplementation among smokers and non-smokers. Post-trial follow-up has already been funded by NCI for CARET, ATBC, the Chinese Cancer Prevention Study, and the two Dartmouth trials of skin cancer and colon polyps. This application proposes to continue by mail the post-trial follow-up of the PHS cohort for 5 years. Continued follow-up of the PHS cohort is particularly important given the unique aspects of the trial, including its large populations of never and ex-smokers which are more representative of the general population of health-conscious individuals who take vitamin supplements, its highly compliant population and record of extremely complete follow-up, its long duration of randomized beta carotene supplementation, and its extremely cost-efficient design for follow-up of a chemoprevention trial cohort.

R01CA040360

1984-12-01

2003-05-31