Challenges in Monitoring the Breast Cancer Prevention Trial

Abstract

The Breast Cancer Prevention Trial (BCPT) was a double-masked, placebo-control, randomized clinical trial designed and conducted by the National Surgical Breast and Bowel Project (NSABP), a National Cancer Institute (NCI)-funded cancer cooperative group. The primary hypothesis tested was whether tamoxifen, a drug that is beneficial for treatment of breast cancer, was effective in preventing the occurrence of cancer in women at increased risk. The Endpoint Review, Safety Monitoring, and Advisory Committee (ERSMAC), the independent data monitoring committee for the BCPT, implemented an innovative monitoring strategy that combined traditional monitoring rules for individual diseases with a global monitoring index in order to weigh the beneficial effects of treatment with known and potential detrimental effects. In addition to developing a monitoring plan tailored for a prevention trial with multiple endpoints of interest, other concerns that were addressed included a reassessment of study sample size and power subsequent to a lengthy suspension of accrual during the trial and handling the occurrence of an unexpected ocular toxicity in association with tamoxifen. Although there were numerous issues that arose during its course, the trial progressed to completion of accrual and successful early termination following the fourth interim analysis, when there was reliable evidence that, not only did tamoxifen prevent breast cancer, but that the beneficial effect outweighed adverse effects of taking tamoxifen.