PHYSICIANS HEALTH STUDY--CONTINUED FOLLOW UP

描述(申请人的描述) 在1996年5月2日出版的《新英格兰医学杂志》上，研究结果 在两项包含β胡萝卜素的大规模随机试验中 出版：医生健康研究(PHS)和贝塔胡萝卜素和 视黄醇疗效试验(CARET)。在小灵通中，对22,071名美国男性进行了调查 医生们，在平均补充12年的Beta后 胡萝卜素或安慰剂，两组之间在 恶性肿瘤、癌症死亡率、心血管死亡率或 各种原因造成的死亡。在Caret的研究中，18,314名男性和女性在高中 因吸烟或接触石棉而患肺癌的风险被分配到 β-胡萝卜素和视黄醇的结合。这场审判提前结束了 其数据监测委员会的主要原因是无法 表现出好处，但也因为观察到可能增加的风险 肺癌、心血管疾病死亡率和总死亡率的一致性 α-生育酚/β-胡萝卜素预防癌症的结果 研究(ATBC)。在国家癌症协会召开的新闻发布会上 研究所(NCI)1996年1月17日，NCI主任理查德·克劳斯纳博士 强调继续对审判采取后续行动至关重要 一群人。鉴于ATBC和Caret的意外结果，以及对 小灵通中的β胡萝卜素没有影响，所有这些都在继续监测 试验队列对于确保完整的长期记录至关重要。 补充β胡萝卜素对健康的影响。为了帮助实现这一目标， 我们已经成立了抗氧化剂试验者合作小组， 将对出版后的结果进行系统的荟萃分析 继续跟踪所有已完成的试验，以充分评估 吸烟者和非吸烟者中的β胡萝卜素补充。审判后 NCI已经为Caret、ATBC、中国癌症提供了随访资金 预防研究，以及皮肤癌和结肠癌的两项达特茅斯试验 息肉。本申请建议以邮寄方式继续试行后 小灵通队列随访5年。小灵通的持续跟进工作 考虑到试验的独特方面，队列尤其重要， 包括它的大量从不吸烟者和曾经吸烟者，他们比 具有健康意识的普通人群的代表 以维生素补充剂为例，其高度顺从的人群和记录 非常完整的随访，其持续时间较长的随机β胡萝卜素 补充，及其极具成本效益的后续设计 化学预防试验队列。

DESCRIPTION (Applicant's Description) 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.