Gehan E A, Schneiderman M A
Department of Biomathematics, University of Texas M. D. Anderson Cancer Center, Houston 77030.
Stat Med. 1990 Aug;9(8):871-80; discussion 903-6. doi: 10.1002/sim.4780090803.
The first randomized clinical trial at the National Cancer Institute (NCI), planned in 1954, commenced in 1955 for the treatment of patients with acute leukaemia. The programme in clinical trials at NCI had strong influence from the clinician and administrator, C. Gordon Zubrod, who introduced the randomized clinical trial at NCI and organized the co-operative clinical trials programme of the Cancer Chemotherapy National Service Center (CCNSC) beginning about 1955. The biostatistician, Marvin Schneiderman, collaborated on the first randomized trials in acute leukaemia and solid tumours and recruited the biostatisticians and statistical centres in the early phase of the co-operative clinical trials programme of the CCNSC. From the beginning, there was acceptance of the principles of the randomization of patients and the statistical analysis of data. The sequence of clinical trials for a new agent included the non-randomized phase I (dosage finding) and phase II (preliminary efficacy) trials as well as the phase III (comparison of treatments) trials. New concepts for the treatment of patients developed from 1955 to the mid-1960s included the combination of therapies with independent activity to increase response rates and the administration of therapy to patients in a disease-free (remission) state to prolong the disease-free state. Methodological developments related to clinical trials up to the mid-1960s included: a plan for phase II trials (Gehan); a generalization of the Wilcoxon test for the comparison of survival distributions with right-censored data (Gehan); a test of proportional hazards for survival distributions, which later became known as the Mantel-Haenszel test (Mantel), and an exponential regression model with an explanatory variable (Feigl and Zelen).
美国国立癌症研究所（NCI）的首个随机临床试验于1954年规划，1955年开始，用于治疗急性白血病患者。NCI的临床试验项目受到临床医生兼管理人员C. 戈登·祖布罗德的强烈影响，他在NCI引入了随机临床试验，并于1955年左右组织了癌症化疗国家服务中心（CCNSC）的合作临床试验项目。生物统计学家马文·施奈德曼参与了急性白血病和实体瘤的首个随机试验，并在CCNSC合作临床试验项目的早期阶段招募了生物统计学家和统计中心。从一开始，患者随机化原则和数据统计分析就得到了认可。一种新药物的临床试验顺序包括非随机的I期（剂量探索）和II期（初步疗效）试验以及III期（治疗比较）试验。1955年至20世纪60年代中期，治疗患者的新概念包括联合具有独立活性的疗法以提高缓解率，以及对处于无病（缓解）状态的患者进行治疗以延长无病状态。到20世纪60年代中期，与临床试验相关的方法学进展包括：II期试验计划（盖汉）；用于比较带有右删失数据的生存分布的威尔科克森检验的推广（盖汉）；一种用于生存分布的比例风险检验，后来被称为曼特尔 - 亨泽尔检验（曼特尔），以及一个带有解释变量的指数回归模型（费格尔和泽伦）。
