emaxPrior.control {clinDR} R 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 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.

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?>

fitEmaxB