Stopping or reporting early for positive results in randomized clinical trials: the National Cancer Institute Cooperative Group experience from 1990 to 2005.
Randomized clinical trials are designed with stopping boundaries to guide data monitoring committees with their decision making concerning ongoing trials. In particular, when extremely positive results are seen and a boundary is crossed, the data monitoring committee may recommend releasing the results earlier to the public than at the definitive final analysis time specified in the protocol. For trials that are still accruing, this also means stopping accrual. Because the information about treatment efficacy is more limited in an early analysis than in a final analysis, questions have been raised about the appropriateness of incorporating early stopping for positive results in trial designs. In particular, there are concerns that treatment effects seen early may not be real or may be overly optimistic. To examine this issue, we collected information about treatment efficacy on National Cancer Institute Cooperative Group trials that were stopped early for positive results (information both at the time the trial was stopped/released and at times of further follow-up). Twenty-seven such trials were located. For 17 of 18 of these trials with sufficient follow-up information, the treatment effect was similar or only slightly smaller at last follow-up compared with the stopping/release time. We critically evaluate reasons why one might be concerned about early stopping for positive results. We conclude that for trials with well-designed interim monitoring plans, the ability to stop early for positive results is an important component of the trial design, allowing the public to benefit as soon as possible from the study conclusions.
Korn
Edward L
EL
Biometric Research Branch and the Clinical Investigations Branch, Cancer Therapy Evaluation Program, Division of Cancer Treatment and Diagnosis, National Cancer Institute, NIH, Bethesda, MD 20892, USA. korne@ctep.nci.nih.gov
Freidlin
Boris
B
Mooney
Margaret
M
D026661:Clinical Trials Data Monitoring Committees; D006801:Humans; D054547:National Cancer Institute (U.S.); D016032:Randomized Controlled Trials as Topic; D012107:Research Design / Q000592:standards; D016896:Treatment Outcome; D014481:United States