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Hy's Law Plot

Source: R/g_hy_law.R
g_hy_law.Rd

A scatter plot typically used to display maximum total bilirubin values (TBL) versus maximum alanine transaminase (ALT) values.

Usage

g_hy_law(
  id,
  term,
  aval,
  arm,
  term_selected,
  anrhi,
  folds = c(3, 2),
  text = c("Normal Range", "Hyperbilirubinemia", "Possible Hy's Law Range",
    "Temple's Corollary"),
  caption = paste("Maximum values are those maximum values that occur post-baseline",
    "(no time constraints and not necessarily concurrent events)."),
  title = "Max. Total Bilirubin vs. Max. Alanine Aminotransferase",
  xlab = "Maximum Alanine Aminotransferase (/ULN)",
  ylab = "Maximum Total Bilirubin (/ULN)"
)

Arguments

id

unique subject identifier.

term

the term of the observation.

aval

analysis value.

arm

treatment arm. Used as fill color in the plot.

term_selected

string vector of length 2 - the two terms selected to be used in the plot. First value corresponds to parameter plotted on the x-axis. Second value corresponds to that plotted on the y-axis.

anrhi

the high limit of normal range.

folds

numeric vector of length two. Indicates the position of the reference lines to be drawn. Default c(3, 2) corresponds to a line at position 3 on the x-axis and 2 on the y-axis.

text

string vector of length four with the label to be shown on each quadrant. First value corresponds to label shown in the bottom left quadrant. Subsequent values move through the graph clockwise.

caption

string of text for footnote. Details of methodology can be shown here.

title

string of text for plot title.

xlab

string of text for x axis label.

ylab

string of text for y axis label.

Value

plot object

Details

This graphic is based upon the eDISH (evaluation of Drug Induced Serious Hepatotoxicity) plot of Watkins et. al. in a 2008 publication from Hepatology. Maximum values are defined as the maximum post-baseline value at any time during the entire length of the observation period. Both axes are in log scale to control for the dispersion of the data. The values are plotted in 'times upper limit of normal' where a value of 1 would mean that the result was normal. Any value above or below 1 would be considered above the upper limit or normal or below the upper limit of normal respectively. For instance, a value of 3 would be read as '3 times the upper limit of normal'. Reference lines are included to determine various states, based upon clinical interpretation of the values and includes the following:

  • Hyperbilirubinemia TBL at least 2 xULN and ALT less than 3 xULN

  • Normal Range TBL <= 1 xULN and ALT <= 1 xULN

  • Temple’s Corollary TBL <= 1 xULN and ALT at least 3 xULN

  • Possible Hy's Law TBL at least 2 xULN and ALT at least 3 xULN

This plot can easily be adjusted for other lab parameters and reference ranges as needed. Consultation with a clinical expert to determine which associations would be clinically meaningful and how to interpret those associations is recommended.

There is no equivalent STREAM output.

Author

Katie Withycombe (withycok) katie.withycombe@roche.com

Amy Franklin (frankla4) amy.franklin@roche.com

William Holmes (holmesw) william.holmes@roche.com

Examples

library(dplyr)
library(nestcolor)

# Note: CRP is being used in place of Bilirubin here because this is the only available data
adsl <- osprey::rADSL
adlb <- osprey::rADLB %>% mutate(ANRHI = 50)

# Example 1, - Hy's law template (3 and 2 X ULN)
g_hy_law(
  id = adlb$USUBJID,
  term = adlb$PARAMCD,
  aval = adlb$AVAL,
  arm = adlb$ARM,
  term_selected = c("ALT", "CRP"),
  anrhi = adlb$ANRHI,
  folds = c(3, 2),
  text = c("Normal Range", "Hyperbilirubinemia", "Possible Hy's Law Range", "Temple's Corollary"),
  caption = paste(
    "Maximum values are those maximum values that occur",
    "post-baseline (no time constraints and not necessarily concurrent events)."
  ),
  title = "Max. Total Bilirubin vs. Max. Alanine Aminotransferase",
  xlab = "Maximum Alanine Aminotransferase (/ULN)",
  ylab = "Maximum Total Bilirubin (/ULN)"
)
#> Warning: All aesthetics have length 1, but the data has 400 rows.
#> ℹ Please consider using `annotate()` or provide this layer with data containing
#>   a single row.
#> Warning: All aesthetics have length 1, but the data has 400 rows.
#> ℹ Please consider using `annotate()` or provide this layer with data containing
#>   a single row.
#> Warning: All aesthetics have length 1, but the data has 400 rows.
#> ℹ Please consider using `annotate()` or provide this layer with data containing
#>   a single row.
#> Warning: All aesthetics have length 1, but the data has 400 rows.
#> ℹ Please consider using `annotate()` or provide this layer with data containing
#>   a single row.


# Example 2, - change the quadrant lines and labels
g_hy_law(
  id = adlb$USUBJID,
  term = adlb$PARAMCD,
  aval = adlb$AVAL,
  arm = adlb$ARM,
  term_selected = c("ALT", "CRP"),
  anrhi = adlb$ANRHI,
  folds = c(10, 15),
  text = c("Quadrant 1", "Quadrant 2", "Quadrant 3", "Quadrant 4"),
  caption = paste(
    "Maximum values are those maximum values that occur",
    "post-baseline (no time constraints and not necessarily concurrent events)."
  ),
  title = "Max. Total Bilirubin vs. Max. Alanine Aminotransferase",
  xlab = "Maximum Alanine Aminotransferase (/ULN)",
  ylab = "Maximum Total Bilirubin (/ULN)"
)
#> Warning: All aesthetics have length 1, but the data has 400 rows.
#> ℹ Please consider using `annotate()` or provide this layer with data containing
#>   a single row.
#> Warning: All aesthetics have length 1, but the data has 400 rows.
#> ℹ Please consider using `annotate()` or provide this layer with data containing
#>   a single row.
#> Warning: All aesthetics have length 1, but the data has 400 rows.
#> ℹ Please consider using `annotate()` or provide this layer with data containing
#>   a single row.
#> Warning: All aesthetics have length 1, but the data has 400 rows.
#> ℹ Please consider using `annotate()` or provide this layer with data containing
#>   a single row.