Output Tab Descriptions | Clinical | Scatterplots

Scatterplots
The Scatterplots tab contains the following elements:
One Scatterplot Matrix of Hy's Law Lab Tests.
Tip: Adjust the size of the scatterplot matrix using the Frame Size slider, located at the upper left corner of the tab.
This plot shows maximum laboratory values for the Alanine Aminotransferase ( ALT), Aspartate Aminotransferase ( AST ), Total Bilirubin (BILI), and Alkaline Phosphatase (ALP) laboratory tests. The values are log2 transformed (this can be changed to log10 or no transformation in the process dialog) and normalized by the Upper Limit of Normal (LBSTNRHI). Reference lines are drawn by default at 3*ULN for ALT and AST and 2*ULN for BILI and ALP. These reference limits can be customized on the dialog.
These limits are also used to create the Hy's Law indicator flag. Subjects with a test value exceeding 3*ULN for ALT or AST (signs of hepatocellular injury) accompanied or followed by elevation of 2*ULN or greater for the BILI test will have a "Yes" value for the Hys Law Case variable created. A note defining the Hy's Law flag is located above the scatterplot matrix. For example, with the default settings the note is as follows: "Hys Law Cases are flagged if ALT or AST >= 3*ULN and BILI >= 2*ULN within 0 Days of ALT/AST peak." You can change the number of days following ALT/AST elevation for which to look for BILI elevation to flag possible Hy's Law cases on the process dialog. Subjects in the plot are colored by the Hy's Law criteria (red for "Yes", blue for "No") and marked by their treatment arm. You can choose to label the quadrants of Hy's Law (Cholestasis, Hy's Law, and Temple's Corollary) in the bottom left scatterplot through a check box option on the dialog.
Two Contingency Analyses.
Two contingency analyses are shown in addition to the scatterplot matrix if any subjects were flagged as Hy's Law or if subjects experienced elevated ALT/AST tests. The first contingency analysis shows a Mosaic Plot and count matrix (Contingency Table) of how many days subjects were experiencing lab test elevations that met the Hy's Law flag across treatment arms. This plot and analysis can give valuable insight into the severity and duration of lab test elevation that could signify liver injury. The second contingency analysis compares the incidence of subjects who experience hepatocellular injury (ALT/AST elevation >= 3*ULN or as defined by dialog option) across treatment arm. A statistical test is provided along with counts that can signify if there is a statistically significant higher number of subjects experiencing liver injury while on the drug versus the placebo. This can give insight into possible drug induced liver injury issues.
The Scatterplot Matrix and the Mosaic Plots in the Contingency Analyses are interactive and linked. You can select subjects in the scatterplot or in the colored boxes of the mosaic plot to see where they lie in the analysis. For example, it might be useful to select the boxes in the mosaic plot for the Days in Hys Law contingency analysis for the treatment group to see the max lab values for those subjects in the scatterplots. In addition, you can select the points using the values of the Hys Law Case and Treatment legend on the scatterplot. Once subjects are selected, you can choose from any of the Action Button drill-downs (Cluster Subjects and Profile Subjects are highly informative to look at the subjects' entire safety profiles) to further explore possibly liver injury safety issues in the trial.