plotB {clinDR}

Plot Bayes dose response curve and dose group means

Description

Plot a dose response curve fit by Bayes MCMC methods (with optional posterior interval bars). Also plot dose group means (with optional CI bars)

Usage

plotB(y, 
	dose, 
	parm, 
	sigma2,
	count=rep(1,length(y)),
	dgrid=sort(unique(c(seq(0,max(dose),length=50), dose))),
	predict= TRUE,plotDif=FALSE,plotMed=FALSE,
	plotResid=FALSE,clev=0.9,
	binary=c('no','logit','probit','BinRes'),BinResLev,
	BinResDir=c('>','<'),
	activeControl=FALSE,ac,yac,
	countac=rep(1,length(yac)),
	labac='Act Comp',shapeac=8,colac='red',
	symbol,symbolLabel='Group',symbolShape=8,
	symbolColor='red',symbolSize=4,
	xlim,ylim,xat=NULL,xlab="Dose",
	ylab=ifelse(plotDif,"Diff with Comparator","Mean"),
	modelFun=emaxfun,makePlot=TRUE,
	...)

Arguments

y

Outcomes, which may be sample means (see counts). LSmeans from a saturated anacova model can be supplied, in which case it is assumed that the Bayesian dose response model also included the additive baseline covariates.

dose

Doses corresponding to outcomes

parm

Matrix of simultated parameter values (each row is a simulated parameter vector). The parm values must be constructed for use in the model function modFun. The default is a 4-parameter Emax model with parameters (log(ED50),lambda,Emax,E0). For a 3-parameter model, set lambda=1 for each simulated parameter vector.

sigma2

Simulated draws from the residual variance (assumed additive, homogeneous). The length of sigma2 must be the same as the number of rows of parm. Set sigma2 to all ones for binary data.

count

Sample sizes for means-only summarized data.

dgrid

The Bayes posterior summaries are evaluated and plotted on the dgrid dosing values

predict

If TRUE(default), the plotted intervals are predictive intervals for the dose group sample means.

plotDif

Plot difference between doses and placebo. It is assumed the lowest dose is placebo. If activeControl, the difference is with the active control mean, and the active controls are not plotted.

plotMed

If TRUE, model-based curves are medians rather than means.

plotResid

If TRUE, a plot of the residuals formed from the dose group means minus the posterior dose group means.

clev

Level for confidence and Bayes intervals

binary

If binary is 'logit' or 'probit', y is assumed to be binary and the appropriate backtransformation is applied to the Emax model output. If binary is 'BinRes', the continuous variable y is converted to a binary responder variable using BinResLev and BinResDir. The continuous Emax model output is converted to binary estimation and prediction assuming normally distributed residuals.

BinResLev

A cut level for a responder variable formed from a continuous endpoint. Rates are computed from the (continuous outcome) model parameters assuming normally distributed residuals. The input y variable is converted to a responder variable.

BinResDir

If BinResDir='>', the responder variable is 1 when y is greater than the cut level, otherwise, it is 1 when y is less than the cut level.

activeControl

When TRUE, active comparator data must be supplied. Each dose group (including PBO) are compared to the active comparator rather than PBO.

ac

Simulations from the posterior distribution of the mean response on active comparator. The number of simulations must match those for the dose response model. For binary data, the simulated values must be transformed to the proportion scale. This differs from the simulated model parameters.

yac

Outcomes for the active comparator group. The coding conventions for y are used.

countac

Sample sizes for summarized data corresponding to count.

labac

x-axis label for the active control group.

shapeac

Shape of the symbol for the active control group.

colac

Color of the symbol for the active control group.

symbol

An optional grouping variable for the dose group sample means.

symbolLabel

Label given to symbol in plot legend.

symbolShape

A character vector with names giving the shapes assigned to different levels of variable symbol. If a single shape is specified, it is replicated for all dose groups. See package ggplot2 for symbol mappings.

symbolColor

A character vector with names giving the colors assigned to different levels of variable symbol. If a single color is specified, it is replicated for all dose groups. See package ggplot2 for color mappings.

symbolSize

The size of the symbol for the dose group sample means. Set symbolSize=0 to supress plotting.

xlim

Plot limits for the x-axis

ylim

Plot limits for the y-axis

xat

The points at which tick-marks are to be drawn. Errors occur if the points are outside the range of xlim. By default (when NULL) tickmark locations are computed.

xlab

x-axis label

ylab

y-axis label

modelFun

The mean model function. The first argument is a scalar dose, and the second argument is a matrix of parameter values. The rows of the matrix are random draws of parameter vectors for the model. The default function is the 4-parameter Emax function emaxfun.

makePlot

If FALSE, create numerical output but no plot.

...

Parameters passed to generic plot function (not used)

Details

A sample of parameters from the joint posterior distribution must be supplied (typically produced by BUGS). The Bayesian dose response curve is the Bayes posterior mean (or median) at each value on dgrid. The bar (interval) is the (clev/2,1-clev/2) Bayes posterior interval (which can differ from the Bayes HPD interval). The intervals are plotted only at the dose levels included in the study. Predictive intervals are formed by adding independent random draws from the sampling distributions of the dose group sample means to the population means.

The function generates random numbers when predict=TRUE, so the random number generator/seed must be set before the function is called for exact reproducibility.

Value

Returns an object of class plotB. Three inputs are saved for later plotting: doses in the original design, dgrid, and clev. The following matrices are saved:

pairwise

The dose group means and their differences with placebo. If a baseline is supplied, the means are lsmeans adjusted to the mean baseline value.

modelABS

Model-based posterior mean, median, posterior (clev/2,1-clev/2) intervals for the population means and sample means. One row per dose group

modelABSG

Same as modelABS but computed on the input grid of doses.

modelDIF

Same as modelABS but with differences from placebo.

modelDIFG

Same as modelDIF but computed on the input grid of doses.

Note

PlotB can also be used with draws from a prior distribution to evaluate the prior dose response curve.

Author(s)

Neal Thomas

References

Spiegelhalter, D., Thomas, A., Best, N., and Lunn, D. (2003), WinBUGS User Manual Version 1.4, Electronic version www.mrc-bsu.cam.ac.uk/bugs

See Also

plot.plotB, plotD, plot.fitEmax

Examples

## Not run: 
data("metaData")
exdat<-metaData[metaData$taid==6 & metaData$poptype==1,]

prior<-emaxPrior.control(epmu=0,epsca=100,difTargetmu=0,difTargetsca=100,dTarget=80.0,
        p50=3.75,sigmalow=0.01,sigmaup=20)
mcmc<-mcmc.control(chains=3)

msSat<-sum((exdat$sampsize-1)*(exdat$sd)^2)/(sum(exdat$sampsize)-length(exdat$sampsize))
fitout<-fitEmaxB(exdat$rslt,exdat$dose,prior,modType=4,
				count=exdat$sampsize,msSat=msSat,mcmc=mcmc)
parms<-coef(fitout)[,1:4]  #use first intercept

outB<-plotB(exdat$rslt,exdat$dose,parms, sigma2=(sigma(fitout))^2,
			ylab="Change in EDD")
			
plot(outB,plotDif=TRUE)

## End(Not run)