Some controversial issues in clinical trials

In clinical development of a test treatment, clinical trials are usually conducted to collect data for evaluation of safety and efficacy of the test treatment under investigation. To provide accurate and reliable assessment, wellcontrolled clinical trials under valid study designs are necessarily conducted. The clinical trial process is lengthy and costly, consisting of protocol development, trial conduct, data collection, statistical analysis and interpretation, and reporting. In practice, some controversial issues are commonly encountered regardless of compliance with good clinical practice. These issues include, but are not limited to, statistical hypotheses for clinical evaluation, instability of classical sample size calculation, integrity of blinding, clinical strategy for endpoint selection, impact of protocol amendments, flexibility and feasibility of adaptive design methods, multiplicity in clinical trials, and independence of data monitoring committees. In this article, these issues are briefly outlined. The impact of these issues on the evaluation of the safety and efficacy of the test treatment under investigation is assessed and discussed with examples whenever applicable. Recommendations regarding possible resolutions of these issues are also provided whenever possible. © 2011 Drug Information Association, Inc.

Duke Scholars

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