The
Scatterplots
tab contains the following elements:
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•
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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 log
2
transformed (this can be changed to log
10
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.
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•
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Two
Contingency Analyses
.
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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 Plot
s
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 (
and
are highly informative to look at the subjects' entire safety profiles) to further explore possibly liver injury safety issues in the trial.