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Gordon Zubrod, who introduced the randomized clinical trial at NCI and organized the co\u2010operative 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\u2010operative 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\u2010randomized 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\u20101960s included the combination of therapies with independent activity to increase response rates and the administration of therapy to patients in a disease\u2010free (remission) state to prolong the disease\u2010free state. Methodological developments related to clinical trials up to the mid\u20101960s included: a plan for phase II trials (Gehan<jats:sup>10<\/jats:sup>); a generalization of the Wilcoxon test for the comparison of survival distributions with right\u2010censored data (Gehan<jats:sup>25<\/jats:sup>); a test of proportional hazards for survival distributions, which later became known as the Mantel\u2010Haenszel test (Mantel<jats:sup>38<\/jats:sup>), and an exponential regression model with an explanatory variable (Feigl and Zelen<jats:sup>41<\/jats:sup>).<\/jats:p>","DOI":"10.1002\/sim.4780090803","type":"journal-article","created":{"date-parts":[[2007,4,26]],"date-time":"2007-04-26T05:49:57Z","timestamp":1177566597000},"page":"871-880","source":"Crossref","is-referenced-by-count":52,"title":["Historical and methodological developments in clinical trials at the national cancer institute"],"prefix":"10.1002","volume":"9","author":[{"given":"Edmund A.","family":"Gehan","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marvin A.","family":"Schneiderman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2006,10,12]]},"reference":[{"key":"e_1_2_1_2_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V13.12.1126.1126"},{"key":"e_1_2_1_3_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM194806032382301"},{"key":"e_1_2_1_4_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1749-6632.1958.tb54908.x"},{"key":"e_1_2_1_5_2","volume-title":"Quantitative Methods in Pharmacology","author":"Schneiderman M. 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