Simulation and Analysis Tools for Clinical Dose Response Modeling

Bayesian and ML Emax model fitting, graphics and simulation for clinical dose response. The summary data from the dose response meta-analyses in Thomas, Sweeney, and Somayaji (2014) and Thomas and Roy (2016) Wu, Banerjee, Jin, Menon, Martin, and Heatherington(2017) are included in the package. The prior distributions for the Bayesian analyses default to the posterior predictive distributions derived from these references.


Changes to clinDR:

Update 1.9

  • Add support for baseline covariates in fitEmax, fitEmaxB and supporting functions
  • Add showStanModels function to display the STAN code for Emax models
  • Corrected output of popSD naming in emaxsim extraction function
  • Consolidated Bayesian Emax models into a single STAN model file.
    Specification of model type (e.g., hyperbolic vs sigmoidal) is no longer required in selEstan and showStanModels functions
  • The 'logit' parameter in function checkMonoEmax was re-named 'binary'
  • Return printed matrices as invisible objects in print.emaxsim(B) and print.emaxsim(B)obj Update 1.8
  • Added testMods of class Mods from R package DoseFinding to the output object of emaxsim(B). testMods gives the functions defining the contrasts for MCP-MOD testing. The ED50contr and lambdacontr that can also be used to define the contrasts were removed.
  • Added coef,sigma, and vcov methods for fitEmax(B), emaxsim(B) objects
  • The summary.emaxsim and summary.emaxsimB functions now return the printed output for extraction. Summaries for the best pairwise comparison were added.
  • Corrected use of specified starting values in function emaxalt and emaxsim.
  • Improved error handling in emaxsim(B) to reset random number generator Update 1.7
  • The calling sequence for 'plotPop' in plot.emaxsimobj and plot.emaxsimBobj have been changed to ensure a valid value is input.
  • The parameter difPlacebo has been renamed plotDif in plot.emaxsim and plot.emaxsimB for consistency with other plotting functions
  • Corrected bug in MCP-MOD test with negative trends
  • Corrected bug causing warning messages from DRDensityPlot when the quantiles have row or column names
  • Corrected plotting of population curve at placebo in plot.emaxsimB Update 1.6
  • Change package dependencies
  • Additional documentation for CRAN release
  • Modify examples for CRAN release Update 1.05
  • Fix bug in parallel processing for emaxsim and emaxsimB
  • Fix bug in residSD input to customCode in emaxsimB Update 1.04
  • RandEmax can now generate random residual SD from a scaled inverted chi distribution Update 1.03
  • Added prediction interval option to plot.emaxsimobj
  • Expanded output from emaxsimB when check=TRUE so test data for custom code can be generated Update 1.02
  • Improved labeling of output of predict.fitEmax(B)
  • Add descriptive label to plot.emaxsim(B) to indicate difference with placebo by default
  • Corrected bug in emaxsim output of residual SD. This impacts predictive intervals from several functions. Update 1.01
  • Major update adding Bayesian versions of fitEmax and emaxsim
  • Supporting methods, e.g., plot, print,... also supplied for new Bayesian functions fitEmaxB and emaxsimB
  • Parallel computing options added for the Bayesian functions Update
  • Added log scale option to plot.plotB.R, plotD.R, plot.fitEmax.R, plot.emaxsimobj.R. If plot=plotDif (difference with placebo) and log=TRUE, the plot starts from the lowest nonzero dose.
  • Improved active control plotting in plot.plotB.R.
  • Added optional user-specified control over x-axis tick marks. Update
  • In checkMonoEmax, included equality in predictive probability calculation.
  • In plot.fitEmax, if there is no grouping variable, then no panel at the top of the plot is created. The function now returns a list with the ggplot2 object and a matrix with the confidence and prediction interval limits. Update
  • Added grouped-data option to checkMonoEmax, and test data.
  • Corrected plotting issue in plotB. Update
  • Updated code for fitEmax test statistics. plot.fitEmax predictive error bars now use the smallest sample size for a dose/strata combination.
  • plotB now returns the ggplot object so it can be further modified.
  • fitEmax can now use non-integer prot variable. Update 0.9.6
  • Added binary logistic Emax model fitting to emaxsim and all associated functions
  • Changed check of the variance-covariance matrix in fitEmax to ensure it is positive definite
  • Eliminated femax and femaxH
  • Replaced RandEmax with skewRandEmax and eliminated the name skewRandEmax Update
  • Corrected bug in predictive interval for binary data in plot.fitEmax Update 0.9.5
  • Added treatment difference option to plot.fitEmax
  • Updated implementation of symbol group in plotB
  • Corrected bugs in prediction intervals in plot.fitEmax
  • Added treatment difference estimation to predict.fitEmax
  • Updated emaxsim and its support functions to use fitemax and its support functions Update 0.9.4
  • Added GOF tests to fitEmax output
  • Fixed symbol bug in plot.fitEmax and plot.logitEmax
  • Fixed fitEmax and logitEmax to return NULL when convergence fails.
  • Created fitEmax to unify fitting of Emax models with continuous/binary data Update 0.9.3
  • Updated all graphic output to use ggplot2
  • Changed order of Emax model parameters to better support fitting of data from multiple protocols with different placebo response. Order of parameters in logitEmax also changed for consistency across all Emax functions.
  • Created new function contEmax to fit continuous emax models using ML estimation along with supporting plot and predict functions
  • Added plot symbol options and residual plots to plot.contEmax and plot.logitEmax
  • Fixed bug in 4-parameter binary data case for startEmax
  • Fixed bug in predictive intervals in plot.logitEmax
  • Changed default confidence/posterior interval levels to 0.90 Update 0.9.2
  • led50 replaces ed50 everywhere.
  • Changed options for skewRandEmax
  • Last version before changes to graphics. Update 0.9.1
  • Numerous changes to DoseResponse package. The biggest change was to eliminate transformation of the Hill parameter.

Reference manual

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2.3.5 by Neal Thomas, 9 months ago

Browse source code at

Authors: Neal Thomas [aut, cre] , Jing Wu [aut] , Mike K. Smith [aut]

Documentation:   PDF Manual  

GPL (>= 2) license

Imports foreach, graphics, ggplot2, DoseFinding, stats, utils, parallel, doParallel, magrittr, purrr, tibble, dplyr, tidyr, glue

Depends on rstan, shiny, waiter

See at CRAN