Control Clin Trials. 1998 Feb;19(1):61-109. doi: 10.1016/s0197-2456(97)00078-0.
The Women's Health Initiative (WHI) is a large and complex clinical investigation of strategies for the prevention and control of some of the most common causes of morbidity and mortality among postmenopausal women, including cancer, cardiovascular disease, and osteoporotic fractures. The WHI was initiated in 1992, with a planned completion date of 2007. Postmenopausal women ranging in age from 50 to 79 are enrolled at one of 40 WHI clinical centers nationwide into either a clinical trial (CT) that will include about 64,500 women or an observational study (OS) that will include about 100,000 women. The CT is designed to allow randomized controlled evaluation of three distinct interventions: a low-fat eating pattern, hypothesized to prevent breast cancer and colorectal cancer and, secondarily, coronary heart disease; hormone replacement therapy, hypothesized to reduce the risk of coronary heart disease and other cardiovascular diseases and, secondarily, to reduce the risk of hip and other fractures, with increased breast cancer risk as a possible adverse outcome; and calcium and vitamin D supplementation, hypothesized to prevent hip fractures and, secondarily, other fractures and colorectal cancer. Overall benefit-versus-risk assessment is a central focus in each of the three CT components. Women are screened for participation in one or both of the components--dietary modification (DM) or hormone replacement therapy (HRT)--of the CT, which will randomize 48,000 and 27,500 women, respectively. Women who prove to be ineligible for, or who are unwilling to enroll in, these CT components are invited to enroll in the OS. At their 1-year anniversary of randomization, CT women are invited to be further randomized into the calcium and vitamin D (CaD) trial component, which is projected to include 45,000 women. The average follow-up for women in either CT or OS is approximately 9 years. Concerted efforts are made to enroll women of racial and ethnic minority groups, with a target of 20% of overall enrollment in both the CT and OS. This article gives a brief description of the rationale for the interventions being studied in each of the CT components and for the inclusion of the OS component. Some detail is provided on specific study design choices, including eligibility criteria, recruitment strategy, and sample size, with attention to the partial factorial design of the CT. Some aspects of the CT monitoring approach are also outlined. The scientific and logistic complexity of the WHI implies particular leadership and management challenges. The WHI organization and committee structure employed to respond to these challenges is also briefly described.
妇女健康倡议（WHI）是一项规模庞大且复杂的临床研究，旨在探寻预防和控制绝经后女性一些最常见发病和死亡原因的策略，这些原因包括癌症、心血管疾病和骨质疏松性骨折。妇女健康倡议始于1992年，计划于2007年完成。年龄在50至79岁之间的绝经后女性在全国40个妇女健康倡议临床中心之一登记参加一项临床试验（CT）或一项观察性研究（OS）。临床试验预计将纳入约64,500名女性，观察性研究预计将纳入约100,000名女性。该临床试验旨在对三种不同干预措施进行随机对照评估：一种低脂饮食模式，推测可预防乳腺癌和结直肠癌，其次预防冠心病；激素替代疗法，推测可降低冠心病和其他心血管疾病的风险，其次降低髋部及其他骨折的风险，但可能会增加患乳腺癌的风险；补充钙和维生素D，推测可预防髋部骨折，其次预防其他骨折和结直肠癌。总体利弊评估是三项临床试验组成部分各自的核心关注点。女性会接受筛查，以确定是否参与临床试验的一个或两个组成部分——饮食调整（DM）或激素替代疗法（HRT），这两项分别将随机纳入48,000名和27,500名女性。被证明不符合条件或不愿参加这些临床试验组成部分的女性将被邀请参加观察性研究。在随机分组满1周年时，参加临床试验的女性会被邀请进一步随机分组进入钙和维生素D（CaD）试验组成部分，该部分预计将纳入45,000名女性。参加临床试验或观察性研究的女性的平均随访时间约为9年。研究团队齐心协力招募少数族裔女性，目标是在临床试验和观察性研究中，少数族裔女性的总体招募人数均占20%。本文简要介绍了在每项临床试验组成部分中所研究干预措施的基本原理以及纳入观察性研究组成部分的理由。还提供了一些关于具体研究设计选择的细节，包括入选标准、招募策略和样本量，并重点关注了临床试验的部分析因设计。同时也概述了临床试验监测方法的一些方面。妇女健康倡议在科学和后勤方面的复杂性意味着存在特殊的领导和管理挑战。本文还简要介绍了为应对这些挑战所采用的妇女健康倡议组织和委员会结构。
