Data Safety and Monitoring Board

All clinical trials that involve more than minimal risk are required to have a Data Safety and Monitoring Board (DSMB), which is an independent board of experts not involved in the study who periodically review the data in a trial to evaluate safety, study conduct, and interim results. They can recommend that the study be continued, modified, or terminated. The DSMB for the Physicians' Health Study recommended that the study be terminated after five years because the benefits of taking low-dose aspirin were so clear that continuing to withhold aspirin from the placebo group was not ethically justified. The DSMB felt that equipoise no longer existed.

Intention-to-Treat Analysis versus Efficacy Analysis

The greatest advantage of large randomized clinical trials is that they provide control of confounding. However, as already noted there can be problems due to loss to follow up and lack of adherence to the protocol. It might be tempting to limit the analysis to subjects who completed the study and who adhered to the study protocol, but this efficacy analysis may not provide strong control of confounding, because subjects have, in essence, self-selected whether they would remain in the study and adhere to the protocol. For this reason, well-done clinical trials will conduct and report the results of an intention-to-treat analysis in which subjects are included in the analysis in the groups to which they were randomly assigned regardless of whether they adhered to the protocol. We already noted that non-adherence will bias the results toward the null, i.e., underestimate the association if there is one. However, the intention-to-treat analysis provides the best opportunity to examine the association in the absence of confounding. Many reports will provide the results of the intention-to-treat analysis and the efficacy analysis as well, and they may also analyze sub-groups of subjects, but these analyses need to use other methods to minimize the effects of confounding.