clinDR: emaxPrior.control – R documentation

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clinDR

emaxPrior.control

Set the parameters of the prior distribution for the Emax model implemented in fitEmaxB.

Description

Set the parameters of the prior distribution for the Emax model implemented in fitEmaxB..

Usage

emaxPrior.control(epmu=NULL,epsca=NULL,
	difTargetmu=NULL,difTargetsca=NULL,
	dTarget=NULL,p50=NULL,
	sigmalow=NULL,sigmaup=NULL,
	effDF=parmDF,parmDF=5,
	loged50mu=0.0,loged50sca=1.73,
	loglammu=0.0,loglamsca=0.425,parmCor=-0.45,
	basemu=NULL,basevar=NULL,binary=FALSE)

Arguments

`epmu`	Mean for `E0` in a t-prior distribution. Logistic scale for binary data.
`epsca`	The scale parameter for `E0` in a t-prior distribution. Logistic scale for binary data.
`difTargetmu`	Mean for the prior distribution of the effect at dose `dTarget` versus placebo. Logistic scale for binary data.
`difTargetsca`	The scale parameter for the prior distribution of the effect at dose `dTarget` versus placebo. Logistic scale for binary data.
`dTarget`	Target dose for prior effect. Typically the highest dose planned and/or the proof-of-concept dose.
`p50`	Projected `ED50`. See references for its use in creating the prior distribution for the `ED50`.
`sigmalow`	Lower bound for a uniform prior distribution for the residual SD (continuous data).
`sigmaup`	Upper bound for a uniform prior distribution for the residual SD (continuous data).
`effDF`	The degrees of freedom for the log-t prior distributions for the `placebo` and `difTarget` parameters. If a vector of length 2 is specified, the first value is the degrees of freedom for `placebo` and the second for `difTarget`.
`parmDF`	The degrees of freedom of the bivariate log-t prior distribution for the `ED50` and `lambda` parameters.
`loged50mu`	Mean of prior t-distribution for the `log(ED50)`. See references for its default value and interpretation.
`loged50sca`	Scale (analogous to SD) of the prior t-distribution for the `log(ED50)`.
`loglammu`	Mean of prior t-distribution for the Hill parameter lambda. See references for its default value and interpretation.
`loglamsca`	Scale (analogous to SD) of the prior t-distribution for the Hill parameter lambda.
`parmCor`	Correlation for the bivariate log-t prior distribution for the `ED50` and `lambda` parameters.
`basemu`	A vector of prior means for the covariate regression parameters.
`basevar`	The prior variance-covariance matrix for the covariate regression parameters. The covariate regression parameters are apriori independent of the other dose response model parameters.
`binary`	Set to `TRUE` for binary data applications. Used to check for consistency in usage.

Details

The prior distribution is based on meta-analyses of dose response described in the references. The E0 and difTarget parameters have independent t-distribution prior distributions. For binary data, these parameters are computed on the logistic scale. The prior means and scales of these parameters must be assigned compound-specific values. The predicted ED50 at the study design stage must must also be specified as 'P50'. For continuous data, the prior distribution for the residual SD is uniform on a user-specifed scale.

The prior distribution of the log(ED50) has a t-distribution centered at log(P50), with scale, degrees of freedom (parmDF), and offset to the P50, defaulting to values given in the references (these can be changed, but they are difficult to interpret outside the context of the meta-analyses). If modType=4, the prior distribution for the Hill parameter is also t-distribution with parmDF degrees of freedom and corParm correlation with the log(ED50).

Value

List of class emaxPrior of prior parameter values for use in fitEmaxB.

Author(s)

Neal Thomas

References

Thomas, N., Sweeney, K., and Somayaji, V. (2014). Meta-analysis of clinical dose response in a large drug development portfolio, Statistics in Biopharmaceutical Research, Vol. 6, No.4, 302-317. <doi:10.1080/19466315.2014.924876>

Thomas, N., and Roy, D. (2016). Analysis of clinical dose-response in small-molecule drug development: 2009-2014. Statistics in Biopharmaceutical Research, Vol. 6, No.4, 302-317 <doi:10.1080/19466315.2016.1256229>

Wu, J., Banerjee, A., Jin, B., Menon, S., Martin, S., and Heatherington, A. (2017). Clinical dose-response for a broad set of biological products: A model-based meta-analysis. Vol. 9, 2694-2721. <doi:10.1177/0962280216684528?>