Organization and analysis of safety data using a multivariate approach.
The collection of safety data is an important part of clinical trials. These safety data are often described and reported in great detail with expenditure of substantial effort and energy. Because of the wide variety of data that require scrutiny from the safety perspective, however, statistical comparisons of the safety profiles of different treatments often lack focus and structure and result in situations where the comparisons for each individual item lack power and thus are inconclusive. In this paper, we propose to organize the safety data into a more manageable form by consolidating them into a number of K classes characterized by body systems and determined in conjunction with the underlying disease as well as the treatments involved. Within each class, we propose assignment to each patient of an overall intensity grade based on all relevant information. The consolidation of the safety data as proposed provides an informative summary for the safety profile of each treatment. The analysis of such organized data concentrates on comparison of the mean intensity grades for different treatments within the K classes simultaneously with use of scores that reflect the acceptability of the various intensity levels to an individual. Furthermore, we demonstrate that the proposed multivariate comparison has much higher power than the univariate one to detect differences in certain cases. We provide examples to illustrate the proposed procedure.