Moving a randomized clinical trial into an observational cohort

• Published in: Clinical trials (London, England) England), 2013-02, Vol.10 (1), p.131-142
• Main Authors: Goodman, Phyllis J, Hartline, Jo Ann, Tangen, Catherine M, Crowley, John J, Minasian, Lori M, Klein, Eric A, Cook, Elise D, Darke, Amy K, Arnold, Kathryn B, Anderson, Karen, Yee, Monica, Meyskens, Frank L, Baker, Laurence H
• Format: Article
• Language: English
• Subjects: Adult; Aged; Aged, 80 and over; Canada - epidemiology; Cancer; Clinical trials; Clinical Trials Data Monitoring Committees; Cohort Studies; Data Collection; Dietary Supplements; Disease prevention; Drug-Related Side Effects and Adverse Reactions; Endpoint Determination; Follow-Up Studies; Humans; Male; Middle Aged; National Cancer Institute (U.S.); Placebos - administration & dosage; Prostatic Neoplasms - epidemiology; Prostatic Neoplasms - prevention & control; Puerto Rico - epidemiology; Randomized Controlled Trials as Topic; Research Design; Selenium; Selenium - administration & dosage; United States - epidemiology; Vitamin E; Vitamin E - administration & dosage
• ISSN: 1740-7745; 1740-7753
• DOI: 10.1177/1740774512460345

Background The Selenium and Vitamin E Cancer Prevention Trial (SELECT) was a randomized, double-blind, placebo-controlled prostate cancer prevention study funded by the National Cancer Institute (NCI) and conducted by the Southwest Oncology Group (SWOG). A total of 35,533 men were assigned randomly to one of the four treatment groups (vitamin E + placebo, selenium + placebo, vitamin E + selenium, and placebo + placebo). The independent Data and Safety Monitoring Committee (DSMC) recommended the discontinuation of study supplements because of the lack of efficacy for risk reduction and because futility analyses demonstrated no possibility of benefit of the supplements to the anticipated degree (25% reduction in prostate cancer incidence) with additional follow-up. Study leadership agreed that the randomized trial should be terminated but believed that the cohort should be maintained and followed as the additional follow-up would contribute important information to the understanding of the biologic consequences of the intervention. Since the participants no longer needed to be seen in person to assess acute toxicities or to be given study supplements, it was determined that the most efficient and cost-effective way to follow them was via a central coordinated effort. Purpose A number of changes were necessary at the local Study Sites and SELECT Statistical Center to transition to following participants via a Central Coordinating Center. We describe the transition process from a randomized clinical trial to the observational Centralized Follow-Up (CFU) study. Methods The process of transitioning SELECT, implemented at more than 400 Study Sites across the United States, Canada, and Puerto Rico, entailed many critical decisions and actions including updates to online documents such as the SELECT Workbench and Study Manual, a protocol amendment, reorganization of the Statistical Center, creation of a Transition Committee, development of materials for SELECT Study Sites, development of procedures to close Study Sites, and revision of data collection procedures and the process by which to contact participants. Results At the time of the publication of the primary SELECT results in December 2008, there were 32,569 men alive and currently active in the trial. As of 31 December 2011, 17,761 participants had been registered to the CFU study. This number is less than had been anticipated due to unforeseen difficulties with local Study Site institutional review boards (