The analysis of adverse events (AEs) suffers from the problem of dimensionality. It is impossible to predict what AEs will occur on study, and there are often numerous events by study’s end. Typically, the incidence of adverse events is summarized in tables, with events coded by a medical dictionary, such as MedDRA. These preferred terms are grouped by body system or system organ class and presented in order of descending frequency.
Many times, statistical testing may not be performed due to the high likelihood of committing multiple Type I errors (or false positives). Adverse event analyses are presented in numerous tables to reflect overall incidence, incidence by the relationship to study medication or incidence by the severity of event. Additional tables may highlight a subset of AEs of special interest such as ocular adverse events in the study of an ophthalmic agent, or they may subset events for specific periods of time within the clinical trial (for example, treatment phase or off-treatment follow-up). Needless to say, it is difficult to summarize such information to gain a clear understanding of the risk (or benefit) a new therapy may present.
Incidence analyses are straightforward to present graphically in JMP Clinical to highlight differences among the treatments (Figure 1, above). Color is used to indicate the treatment with higher incidence, while bubble size represents the total number of events that occur during the trial. Adjustments for multiple comparisons can be performed and presented in a manner to clearly indicate which events exhibit statistically significant treatment differences between the groups (i.e., those events above the dashed red line). Additionally, with a graphical display, the study can easily be broken into multiple distinct time periods and animation can present changes in adverse event risk over time. This presentation can emphasize early differences across treatments that may eventually resolve or highlight events that could approach significance given a longer study duration.
For more information, feel free to download the following white paper or view this short video.