Surrogate (version 1.1)

plot Meta-Analytic: Provides plots of trial- and individual-level surrogacy in the meta-analytic framework

Description

Produces plots that provide a graphical representation of trial- and/or individual-level surrogacy based on the meta-analytic approach of Buyse & Molenberghs (2000) in the single- and multiple-trial settings.

Usage

# S3 method for BifixedContCont
plot(x, Trial.Level=TRUE, Weighted=TRUE, 
Indiv.Level=TRUE, ICA=TRUE, Entropy.By.ICA=FALSE, Xlab.Indiv, Ylab.Indiv, 
Xlab.Trial, Ylab.Trial, Main.Trial, Main.Indiv, Par=par(oma=c(0, 0, 0, 0), 
mar=c(5.1, 4.1, 4.1, 2.1)), …)
# S3 method for BimixedContCont
plot(x, Trial.Level=TRUE, Weighted=TRUE, 
Indiv.Level=TRUE, ICA=TRUE, Entropy.By.ICA=FALSE, Xlab.Indiv, Ylab.Indiv, 
Xlab.Trial, Ylab.Trial, Main.Trial, Main.Indiv, Par=par(oma=c(0, 0, 0, 0), 
mar=c(5.1, 4.1, 4.1, 2.1)), …)
# S3 method for UnifixedContCont
plot(x, Trial.Level=TRUE, Weighted=TRUE, 
Indiv.Level=TRUE, ICA=TRUE, Entropy.By.ICA=FALSE, 
Xlab.Indiv, Ylab.Indiv, Xlab.Trial, Ylab.Trial, 
Main.Trial, Main.Indiv, Par=par(oma=c(0, 0, 0, 0), 
mar=c(5.1, 4.1, 4.1, 2.1)), …)
# S3 method for UnimixedContCont
plot(x, Trial.Level=TRUE, Weighted=TRUE, 
Indiv.Level=TRUE, ICA=TRUE, Entropy.By.ICA=FALSE, 
Xlab.Indiv, Ylab.Indiv, Xlab.Trial, Ylab.Trial, 
Main.Trial, Main.Indiv, Par=par(oma=c(0, 0, 0, 0), 
mar=c(5.1, 4.1, 4.1, 2.1)), …)

Arguments

x

An object of class UnifixedContCont, BifixedContCont, UnimixedContCont, BimixedContCont, or Single.Trial.RE.AA.

Trial.Level

Logical. If Trial.Level=TRUE and an object of class UnifixedContCont, BifixedContCont, UnimixedContCont, or BimixedContCont is considered, a plot of the trial-specific treatment effects on the true endpoint against the trial-specific treatment effect on the surrogate endpoints is provided (as a graphical representation of \(R_{trial}\)). If Trial.Level=TRUE and an object of class Single.Trial.RE.AA is considered, a plot of the treatment effect on the true endpoint against the treatment effect on the surrogate endpoint is provided, and a regression line that goes through the origin with slope RE is added to the plot (to depict the constant RE assumption, see Single.Trial.RE.AA for details). If Trial.Level=FALSE, this plot is not provided. Default TRUE.

Weighted

Logical. This argument only has effect when the user requests a trial-level surrogacy plot (i.e., when Trial.Level=TRUE in the function call) and when an object of class UnifixedContCont, BifixedContCont, UnimixedContCont, or BimixedContCont is considered (not when an object of class Single.Trial.RE.AA is considered). If Weighted=TRUE, the circles that depict the trial-specific treatment effects on the true endpoint against the surrogate endpoint are proportional to the number of patients in the trial. If Weighted=FALSE, all circles have the same size. Default TRUE.

Indiv.Level

Logical. If Indiv.Level=TRUE, a plot of the trial- and treatment-corrected residuals of the true and surrogate endpoints is provided (when an object of class UnifixedContCont, BifixedContCont, UnimixedContCont, or BimixedContCont is considered), or a plot of the treatment-corrected residuals (when an object of class Single.Trial.RE.AA is considered). This plot provides a graphical representation of \(R_{indiv}\). If Indiv.Level=FALSE, this plot is not provided. Default TRUE.

ICA

Logical. Should a plot of the individual level causal association be shown? Default ICA=TRUE.

Entropy.By.ICA

Logical. Should a plot that shows ICA against the entropy be shown? Default Entropy.By.ICA=FALSE.

Xlab.Indiv

The legend of the X-axis of the plot that depicts individual-level surrogacy. Default "Residuals for the surrogate endpoint (\(\varepsilon_{Sij}\))" (without the \(i\) subscript when an object of class Single.Trial.RE.AA is considered).

Ylab.Indiv

The legend of the Y-axis of the plot that depicts individual-level surrogacy. Default "Residuals for the true endpoint (\(\varepsilon_{Tij}\))" (without the \(i\) subscript when an object of class Single.Trial.RE.AA is considered).

Xlab.Trial

The legend of the X-axis of the plot that depicts trial-level surrogacy. Default "Treatment effect on the surrogate endpoint (\(\alpha_{i}\))" (without the \(i\) subscript when an object of class Single.Trial.RE.AA is considered).

Ylab.Trial

The legend of the Y-axis of the plot that depicts trial-level surrogacy. Default "Treatment effect on the true endpoint (\(\beta_{i}\))" (without the \(i\) subscript when an object of class Single.Trial.RE.AA is considered).

Main.Indiv

The title of the plot that depicts individual-level surrogacy. Default "Individual-level surrogacy" when an object of class UnifixedContCont, BifixedContCont, UnimixedContCont, or BimixedContCont is considered, and "Adjusted Association (\(rho_{Z}\)) when an object of class Single.Trial.RE.AA is considered.

Main.Trial

The title of the plot that depicts trial-level surrogacy. Default "Trial-level surrogacy" (when an object of class UnifixedContCont, BifixedContCont, UnimixedContCont, or BimixedContCont is considered) or "Relative Effect (RE)" (when an object of class Single.Trial.RE.AA is considered).

Par

Graphical parameters for the plot. Default par(oma=c(0, 0, 0, 0), mar=c(5.1, 4.1, 4.1, 2.1)).

…

Extra graphical parameters to be passed to plot().

References

Buyse, M., Molenberghs, G., Burzykowski, T., Renard, D., & Geys, H. (2000). The validation of surrogate endpoints in meta-analysis of randomized experiments. Biostatistics, 1, 49-67.

See Also

UnifixedContCont, BifixedContCont, UnifixedContCont, BimixedContCont, Single.Trial.RE.AA

Examples

# NOT RUN {
 # time consuming code part
##### Multiple-trial setting

## Load ARMD dataset
data(ARMD)

## Conduct a surrogacy analysis, using a weighted reduced univariate fixed effect model:
Sur <- UnifixedContCont(Dataset=ARMD, Surr=Diff24, True=Diff52, Treat=Treat, Trial.ID=Center, 
Pat.ID=Id, Number.Bootstraps=100, Model=c("Reduced"), Weighted=TRUE)

## Request both trial- and individual-level surrogacy plots. In the trial-level plot,
## make the size of the circles proportional to the number of patients in a trial:
plot(Sur, Trial.Level=TRUE, Weighted=TRUE, Indiv.Level=TRUE)

## Make a trial-level surrogacy plot using filled blue circles that 
## are transparent (to make sure that the results of overlapping trials remain
## visible), and modify the title and the axes labels of the plot: 
plot(Sur, pch=16, col=rgb(.3, .2, 1, 0.3), Indiv.Level=FALSE, Trial.Level=TRUE, 
Weighted=TRUE, Main.Trial=c("Trial-level surrogacy (ARMD dataset)"), 
Xlab.Trial=c("Difference in vision after 6 months (Surrogate)"),
Ylab.Trial=c("Difference in vision after 12 months (True enpoint)"))

## Add the estimated R2_trial value in the previous plot at position (X=-7, Y=11)  
## (the previous plot should not have been closed):
R2trial <- format(round(as.numeric(Sur$Trial.R2[1]), 3))
text(x=-7, y=11, cex=1.4, labels=(bquote(paste("R"[trial]^{2}, "="~.(R2trial)))))

## Make an Individual-level surrogacy plot with red squares to depict individuals
## (rather than black circles):
plot(Sur, pch=15, col="red", Indiv.Level=TRUE, Trial.Level=FALSE)

## Same plot as before, but now with smaller squares, a y-axis with range [-40; 40], 
## and the estimated R2_indiv value in the title of the plot:
R2ind <- format(round(as.numeric(Sur$Indiv.R2[1]), 3))
plot(Sur, pch=15, col="red", Indiv.Level=TRUE, Trial.Level=FALSE, cex=.5, 
ylim=c(-40, 40), Main.Indiv=bquote(paste("R"[indiv]^{2}, "="~.(R2ind))))


##### Single-trial setting

## Conduct a surrogacy analysis in the single-trial meta-analytic setting:
SurSTS <- Single.Trial.RE.AA(Dataset=ARMD, Surr=Diff24, True=Diff52, Treat=Treat, Pat.ID=Id)

# Request a plot of individual-level surrogacy and a plot that depicts the Relative effect 
# and the constant RE assumption:
plot(SurSTS, Trial.Level=TRUE, Indiv.Level=TRUE)
# }