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

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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. PAGE 164
CHAPTER 10 ST 520, A. TSIATIS and D. Zhang The DSMB generally has members who represent the following disciplines: • Clinical • Laboratory • Epidemiology • Biostatistics • Data Management • Ethics The members of the DSMB should have no conflict of interest with the study or studies they are monitoring; e.g. no financial holdings in the company that is developing the treatments by member or family. All the discussions of the DSMB are confidential. The charge of the DSMB includes: • Protocol review • Interim reviews – study progress – quality of data – safety – efficacy and benefit • Manuscript review During the early stages of a clinical trial the focus is on administrative issues regarding the conduct of the study. These include: • Recruitment/Entry Criteria • Baseline comparisons PAGE 165
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ST 520 Statistical Principles of Clinical Trials - NCSU Statistics ...

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