Halperin M, DeMets D L, Ware J H
George Washington University, Biostatistics Center, Rockville, MD 20852.
Stat Med. 1990 Aug;9(8):881-92; discussion 903-6. doi: 10.1002/sim.4780090804.
The National Heart Institute, now known as the National Heart, Lung and Blood Institute (NHLBI), initiated its first multicentre randomized clinical trials of rheumatic fever and rheumatic heart disease in 1951. The modern era of multicentre trials began, however, when the Coronary Drug Project was initiated in the 1960s. This trial and subsequent NHLBI trials stimulated a wide variety of research on clinical trial methodology. This paper reviews early methodologic developments in four areas. First, an organizational structure for multicentre clinical trials was developed and codified in the 'Greenberg Report' in 1967. Second, design considerations related to patient risk, non-compliance, a lag in treatment effect, and changing risk were explored. The 'intention-to-treat' principle was implicit in these investigations. Thirdly, the concept of periodic review of accumulating data, recommended in the Greenberg report, stimulated research on methods for sequential analysis. Three statistical approaches were developed and investigation of their statistical properties continues today. These approaches are usually described as group sequential, stochastic curtailment, and Bayesian methods. Finally, comparison of treatments in longitudinal studies has been an increasing part of NHLBI research and methods have been developed for design and analysis of longitudinal studies.
美国国立心脏研究所，现称为国立心脏、肺和血液研究所（NHLBI），于1951年启动了其第一项关于风湿热和风湿性心脏病的多中心随机临床试验。然而，多中心试验的现代时代始于20世纪60年代启动的冠心病药物项目。这项试验以及随后的NHLBI试验激发了对临床试验方法学的广泛研究。本文回顾了四个领域早期的方法学发展。首先，1967年在《格林伯格报告》中制定并编纂了多中心临床试验的组织结构。其次，探讨了与患者风险、不依从性、治疗效果滞后以及风险变化相关的设计考量。“意向性分析”原则在这些研究中是隐含的。第三，《格林伯格报告》中推荐的对累积数据进行定期审查的概念激发了对序贯分析方法的研究。开发了三种统计方法，并且对它们统计特性的研究至今仍在继续。这些方法通常被描述为成组序贯、随机截尾和贝叶斯方法。最后，纵向研究中治疗方法的比较在NHLBI的研究中所占比重日益增加，并且已经开发出了用于纵向研究设计和分析的方法。
