AE (Adverse Events) dotplot of incidence and relative risk

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Description

A three-panel display of the most frequently occurring AEs in the active arm of a clinical study. The first panel displays their incidence by treatment group, with different symbols for each group. The second panel displays the relative risk of an event on the active arm relative to the placebo arm, with 95% confidence intervals for a 2x2 table. By default, the AEs are ordered by relative risk so that events with the largest increases in risk for the active treatment are prominent at the top of the display. By setting the argument sortbyRelativeRisk=FALSE, the AEs retain the order specified by the levels of the factor. The third panel displays the numerical values of number of patients for each treatment, number of adverse events for each treatment, and relative risk. The third panel can be suppressed by the print method.

Usage

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  AEdotplot(xr, ...)

  ## S3 method for class 'formula'
AEdotplot(xr, groups=NULL, data=NULL,
          sortbyRelativeRisk=TRUE,
          ...,
          sub=list(deparse(this.call[1:4],
                                width.cutoff=500), cex=.7))

Arguments

xr

For the formula method, a formula of the form AE ~ nAE/nTRT | OrgSys, where the condition variable is optional. For the formula method only, the variable names are not restricted. See AEdotplot.data.frame for the support methods.

groups

Variable containing the treatment levels.

data

data.frame containing at least four variables: containing the AE name as a factor, the treatment level as a factor, the number of observed AE in that treatment level, the number of patients in that treatment group. It may also contain a fifth variable containing a condition variable used to split the data.frame into partitions. It may be used to partition the plot, for example by organ system or by gender. The treatment factor must have exactly two levels. Each AE name must appear exactly once for each level of the treatment.

sortbyRelativeRisk

logical. If TRUE, then make the Adverse Events an ordered factor ordering by relative risk. If FALSE, then make the Adverse Events an ordered factor retaining the order of the input levels.

sub

Subtitle for the plot. The default value is the command that generates the plot.

...

Any of the arguments (such as the sorting options) listed in the calling sequence for the methods documented in AEdotplot.data.frame.

Details

The first panel is an ordinary dotplot of the percent of AE observed for each treatment by AE.

The second panel shows relative risk of an event on the Treatment B arm (usually the active compound) relative to the Treatment A arm (usually the placebo), with 95% confidence intervals for a 2x2 table. Confidence intervals on the log relative risk are calculated using the asymptotic standard error formula given as Equation 3.18 in Agresti A., Categorical Data Analysis. Wiley: New York, 1990.

By default the AEdotplot function sorts the events by relative risk. To retain the sort order implied by the levels of the AE factor, specify the argument sortbyRelativeRisk=FALSE. To control the sort order, make the AE factor in the input dataset an ordered factor and specify the levels in the order you want.

The third panel shows the numerical values of the number and percent of observed events on each arm and the relative risk. The display of third panel can be suppressed by specifying the panel.widths argument. See the discussion of the panel.widths in AEdotplot.data.frame.

Value

The primary interest is in the display of the plot.

The function returns an AEdotplot object which is a list of three trellis objects, one for the the Percent plot, one for the Relative Risk plot, and one for the Text plot containing the table of input values. The object has attributes

  1. main and sub hold the main and subtitles. Each must be a list containing the text in the first component.

  2. ae.key is a key as described in xyplot.

  3. n.events is a vector containing the number of events in each subpanel.

  4. panel.widths is a vector of relative widths of the three components of the graph. The numbers must sum to one. Zero values are permitted. The first width includes the left axis and the Percent plot. The second is the Relative Risk plot, and the third is the plot of the table values.

  5. AEtable is a table containing the data plotted on its row.

Note

Ann Liu-Ferrara was a beta tester for the shiny app.

Author(s)

Richard M. Heiberger <rmh@temple.edu>

References

Ohad Amit, Richard M. Heiberger, and Peter W. Lane. (2008) “Graphical Approaches to the Analysis of Safety Data from Clinical Trials”. Pharmaceutical Statistics, 7, 1, 20–35. http://www3.interscience.wiley.com/journal/114129388/abstract

See Also

AEdotplot.data.frame

Examples

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## formula method.  See ?AEdotplot.data.frame for other methods.
data(AEdata)
head(AEdata)

AEdotplot(AE ~ nAE/nTRT, groups = TRT, data = AEdata)           ## sort by Relative Risk
AEdotplot(AE ~ nAE/nTRT | OrgSys, groups = TRT, data = AEdata)  ## conditioned on Organ System

## Not run: 
AEdotplot(AE ~ nAE/nTRT, groups = TRT, data = AEdata, sortbyVar="PCT")                   ## PCT A
AEdotplot(AE ~ nAE/nTRT, groups = TRT, data = AEdata, sortbyVar="PCT", sortbyVarBegin=2) ## PCT B
AEdotplot(AE ~ nAE/nTRT, groups = TRT, data = AEdata, sortbyRelativeRisk=FALSE)     ## levels(AE)
AEdotplot(AE ~ nAE/nTRT | OrgSys, groups = TRT, data = AEdata, sortbyVar="ase.logrelrisk")

## End(Not run)


## Not run: 


AEdotplot(AE ~ nAE/nTRT | OrgSys, groups = TRT,
          data = AEdata[c(AEdata$OrgSys %in% c("GI","Resp")),])

## test sortbyRelativeRisk=FALSE
ABCD.12345 <- AEdata[1:12,]
head(ABCD.12345)
AEdotplot(AE ~ nAE/nTRT | OrgSys, groups=TRT, data=ABCD.12345)
AEdotplot(AE ~ nAE/nTRT | OrgSys, groups=TRT, data=ABCD.12345, sort=FALSE)

## suppress third panel
tmp <- AEdotplot(AE ~ nAE/nTRT, groups = TRT, data = AEdata)
print(tmp, AEtable=FALSE)

## End(Not run)

## Not run: 
  ## run the shiny app
  shiny::runApp(system.file("shiny/AEdotplot", package="HH"))

## End(Not run)

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