ST 520 Statistical Principles of Clinical Trials - NCSU Statistics ...

CHAPTER 10 ST 520, A. TSIATIS and D. Zhang
10 Early Stopping of Clinical Trials
10.1 General issues in monitoring clinical trials
Up to now we have considered the design and analysis of clinical trials assuming the data would
be analyzed at only one point in time; i.e. the final analysis. However, due to ethical as well
as practical considerations, the data are monitored periodically during the course of the study
and for a variety of reasons may be stopped early. In this section we will discuss some of the
statistical issues in the design and analysis of clinical trials which allow the possibility of early
stopping. These methods fall under the general title of group-sequential methods.
Some reasons a clinical trial may be stopped early include
• Serious toxicity or adverse events
• Established benefit
• No trend of interest
• Design or logistical difficulties too serious to fix
Since there is lot invested (scientifically, emotionally, financially, etc.) in a clinical trial by
the investigators who designed or are conducting the trial, they may not be the best suited
for deciding whether the clinical trial should be stopped. It has become common practice for
most large scale phase III clinical trials to be monitored by an independent data monitoring
committee; often referred to as a Data Safety Monitoring Board (DSMB). It is the responsibility
of this board to monitor the data from a study periodically (usually two to three times a year)
and make recommendations on whether the study should be modified or stopped. The primary
responsibility of this board is to ensure the safety and well being of the patients that have enrolled
into the trial.
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