Data and safety monitoring in the Concorde and Alpha trials

Concorde was a randomized trial to compare immediate and deferred zidovudine (AZT) treatment for persons with asymptomatic HIV infection. Alpha was a randomized trial to compare the efficacy of two doses of didanosine (ddI), in persons with symptomatic HN disease who were intolerant of zidovudine. The two trials overlapped in time, and a single Data and Safety Monitoring Committee (DSMC) monitored accumulating data from both trials. This paper describes the deliberations of the DSMC and its recommendations to the parent steering committee during the course of each trial. In the discussion on Concorde, I draw attention to the problems of interpreting early survival data and trends in surrogate markers. With Alpha, interest focusses on the conflicting considerations that arose in discussions about possible termination at an interim stage. Control Clin Trials 1999;20:207-228 (C) Elsevier Science Inc. 1999.