Graphical approaches to the analysis of safety data from clinical trials

Patient safety has always been a primary focus in the development of new pharmaceutical products. The predominant method for statistical evaluation and interpretation of safety data collected in a clinical trial is the tabular display of descriptive statistics. There is a great opportunity to enhance evaluation of drug safety through the use of graphical displays, which can convey multiple pieces of information concisely and more effectively than can tables. Graphs can be used in an exploratory setting to help identify emerging safety signals, or in a confirmatory setting as a tool to elucidate known safety issues. We developed several graphical displays for routine safety data collected during a clinical trial, covering a broad range of graphical techniques, and illustrate here 10 specific graphical designs, many of which display the data along with statistics derived from them. Two are simple plots, comparing distributions in the form of boxplots or cumulative plots, and four more display data and summaries over time, comparing information from two groups in terms of distribution (with boxplots), cumulative incidence, hazard, or simply means with error bars. The other four are multi-panel displays: one-dimensional and two-dimensional arrays of scatterplots, a trellis of individual profiles, and a paired dotplot displaying risk together with relative risk. The displays focus on key safety endpoints in clinical trials including the QT interval from electrocardiograms, laboratory measurements for detecting hepatotoxicity, and adverse events of special interest. We discuss in detail the statistical and graphical principles underlying the production and interpretation of the displays.