On the independence of data monitoring committee in adaptive design clinical trials.

In clinical trials, an independent data monitoring committee (DMC) is often established to perform both ongoing safety data monitoring and interim efficacy analysis. These evaluations are performed in a blinded fashion in order to avoid possible operational biases that may be introduced to the trial after the review of the data. The DMCs for clinical trials using adaptive design methods are also positioned to implement the adaptation decision according to the prospective adaptation algorithm. While the DMC plays an important role in maintaining the validity and integrity of the intended clinical trial, adaptive design clinical trials trigger a greater role and increased responsibility for the DMC. To assist the sponsor in establishing a DMC, the U.S. Food and Drug Administration (FDA) published a draft guidance entitled Establishment and Operation of Clinical Trial Data Monitoring Committees in 2006. In this article, the composition, role/responsibility, and function/activity of a DMC are described. Concerns of the additional responsibilities of the DMC for adaptive design clinical trials are addressed. Although the intention of the DMC is well-intentioned, controversial issues inevitably occur. These controversial issues include, but are not limited to, (1) the challenge of the independence of a DMC and (2) the issue regarding the direct communication between the DMC and the FDA. Discussion of controversial issues and practical issues are also provided.

Duke Scholars

Author Gordon Ralph Corey Medicine, Infectious Diseases

Author Shein-Chung Chow Biostatistics & Bioinformatics, Division of Biostatistics