Patient accrual and interim statistical analysis in long-term randomized clinical trials: the French chronic lymphocytic leukemia CLL 80 protocol as a case study.

The CLL 80 clinical trial of treatment for chronic lymphocytic leukemia was designed using a three-stage prognostic classification. Within each stage patients received one of two treatments allocated by randomization, two adjacent stages having a common treatment. The fixed-sample design required 850 patients entered over a period of 8.5 years. Active patient recruitment led to 741 patients being randomized in four years. The first interim analysis, carried out at this point, showed a treatment difference in one stage which was statistically significant (p = 0.001) and justified an early termination of the protocol. This paper discusses practical aspects of patient accrual and interim analysis in this study.