Abstract
During the past four decades, the randomized clinical trial has evolved as a major research methodology for the rigorous evaluation of new medical interventions and therapies. The role of statistics in clinical trial methodology and the organizational structure of clinical trials have also evolved. More recently, there has been a shift in the funding of clinical trials, from the public (eg, National Institutes of Health, or NIH) to the private (pharmaceutical and device industries) sector. This paper describes an Industry-Modified NIH Model for the conduct of industry-sponsored clinical trials that involves a distinct statistical analysis center (SAC) and data management center, as opposed to the single unit, or coordinating center, utilized in most NIH-sponsored trials. The role of the SAC in support of the monitoring activities of an independent data monitoring committee (IDMC) is described in detail. Since the Greenberg Report was published in 1967, the number of multicenter confirmatory clinical trials that have an IDMC has steadily increased, and the recent International Conference on Harmonisation (ICH) E9 regulatory guideline on clinical trials supports this trend. This manuscript provides explicit guidance regarding the activities of an independent SAC for industry-sponsored clinical trials based on our experiences as a SAC for a number of such trials. Activities discussed include protocol development, drafting of written operating procedures for an IDMC and summary notes of its meetings, and preparation of an interim analysis plan and interim analysis reports.