emaxPrior.controlR Documentation

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 parameters implemented in fitEmaxB..

Usage

  emaxPrior.control(mixP=0,epmu=NULL,epsca=NULL,
                    mu_ep=NULL, sd_ep = NULL, w_ep=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,
                    lowled50=log(0.001),highled50=log(1000),
                    lowllam=log(0.3),highllam=log(4.0),
                    basemu=NULL,basevar=NULL,binary=FALSE)

Arguments

mixP

The number of mixture components included in the prior distribution of the placebo response (E0). Each component represents a normal distribution. Set mixP to 0 (default) to specify a multivariate $t$ prior distribution. mixP=1 is not supported. Use a t-prior distribution with high df to specify a normal prior distribution.

mu_ep

For the mixture prior prior, a numeric vector of component means. Each entry gives the mean of the normal distribution associated with that component. Logistic scale for binary data.

sd_ep

For the mixture prior prior, a numeric vector of component standard deviations. Each entry gives the standard deviation of the normal distribution associated with that component. Logistic scale for binary data.

w_ep

For the mixture prior prior, a numeric vector of mixture weights. Each weight specifies the relative contribution of the corresponding component to the overall distribution.

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 the 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 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/P50). See references for its default value and interpretation.

loged50sca

Scale (analogous to SD) of the prior t-distribution for the log(ED50/P50).

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.

lowled50, highled50, lowllam, highllam

Bounds applied to the prior distributions for the log(ED50/P50) and log(lambda). The original (unbounded) priors are modified to be conditional on being within the bounds. This is done for numerical stability and plausibility of the parameter values

basemu

A vector of prior means for the covariate regression parameters. Covariate adjustment with a mixture PBO prior (mixP>0) is not implemented.

basevar

The prior variance-covariance matrix for the covariate regression parameters. The covariate regression parameters are a priori independent of the other dose response model parameters. Covariate adjustment with a mixture PBO prior (mixP>0) is not implemented.

binary

Set to TRUE for binary data applications. Used to check for consistency in usage. The default is FALSE

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).

If mixP>0, any non null value specified under epmu and epsca will be ignored. The model will consider mixture normal distribution alone for E0 prior. The t-distribution will be ignored.

Value

List of class emaxPrior of prior parameter values for use in fitEmaxB. default is a derived variable set to TRUE when the default values are used for loged50 and loglambda.

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?>

See Also

fitEmaxB