DoseFinding 1.4-1

• Added powMCTInterim function to implement conditional/predictive power calculations for interim analyses (#10)
• Added vignette illustrating analysis of longitudinal data (#29, thanks to Daniel Sabanes Bove for work on this and powMCTInterim)
• replaced uses of ggplot2::qplot, which is deprecated (#22)
• Minor updates to documentation and testing (#27 and #30)
• added hex sticker (#28)

DoseFinding 1.3-1

• Added maFitMod function to implement fitting of dose-response models via model averaging (#11, thanks to Björn Bornkamp)
• Fixed the way ED dose estimation works with type = “discrete”. Previously the maximum effect size for ED calculation was taken to be the highest effect among the doses provided as arguments, rather than across the observed dose range for the fitted model (#18)
• replaced uses of ggplot2::aes_string, which is deprecated (#14)
• added additional tests for several functions

DoseFinding 1.2-1

• Documentation revised and updated, documentation now uses roxygen, README and NEWS (replacing old changelog) added
• Former “Depends” packages changed to “Imports”
• nlme added as suggested package
• Marius Thomas is the new maintainer of the package, Novartis Pharma AG added as copyright holder and funder
• Package is now hosted on https://github.com/openpharma/DoseFinding

DoseFinding 1.1-1

• Big thanks to Marius Thomas for adding the bMCTtest function, implementing a generalized version of the Bayesian MCP-Mod methodology from Fleischer et al (2022) (https://doi.org/10.1002/pst.2193)
• Thanks to Sebastian Bossert for feedback on bMCTtest
• Function critVal is now exported

DoseFinding 1.0-5

• Fixed bug in non-exported function powMCTBinCount, for situation when user defined contrast matrix is handed over.
• Added function DesignMCPModApp which starts the externally hosted R-Shiny app DesignMCPMod to perform power and sample size calculations (main authors of the app are Sophie Sun and Danyi Xiong).

DoseFinding 1.0-4

• Added non-exported function powMCTBinCount, for power calculation for binary and count data.

DoseFinding 1.0-3

• Stop and throw error if calculated df=0 in powMCT (passed to mvtnorm where df=0 implies use of a normal distribution)
• Added function plotMods to plot candidate models using ggplot2 and function plotContr to plot optimal contrasts using ggplot2 (thanks to Sophie Sun for testing and feedback)
• Added documentation for quadratic model (definition of delta)
• Fixed local options in guesst for logistic and sigEmax models

DoseFinding 1.0-2

• Define USE_FC_LEN_T and add length of character arguments in Fortran code called from C, to reflect recent changes in gfortran.
• Fix incorrect error message in fitMod (in case placAdj = TRUE and data are handed over in a data frame via data argument)

DoseFinding 1.0-1

• Big thanks to Ludger Sandig, who was instrumental in adding vignettes for practical MCP-Mod implementation guidance; introducing tests based on testthat and further bug fixes.
• Thanks to Dong Xi, Hilke Kracker for review of earlier versions of the draft vignettes
• Thanks to Julia Duda for her helpful comments on the package

DoseFinding 0.9-17

• Added citation to DESCRIPTION file
• Removed alpha argument for pValues function (not used)
• Propagate error messages from mvtnorm in pValues function (e.g. cov-matrix not psd), (thx to Daisy Bai)
• Make direction attribute in Mods object unique (thx to Yuhan Li)

DoseFinding 0.9-16

• Fixed minor bug in print.summary.planMod

DoseFinding 0.9-15

• Mods Added parameter names for all models in the output list (thanks to Dong Xi for catching this)

DoseFinding 0.9-14 * planMod.Rd Documentation slightly extended. * qmvtDF moved back to qmvt function from mvtnorm, as problems in mvtnorm are fixed.

DoseFinding 0.9-13 * projPrBnds now also covers the case when parameter was exactly on the bound * bFitMod doseNam changes * critVal Added self-written qmvt function qmvtDF (as mvtnorm::qmvt got instable on Windows 32bit from release 1.0-3), hopefully superfluous once mvtnorm fixes this.

DoseFinding 0.9-12 * glycobrom dataset: Included column for number of observations per treatment. * calcCrit now takes into account “nold” in determining whether enough design points were specified to be able to calculate the design criteria. * bFitMod documentation for plot.bFitMod and predict.bFitMod methods added. coef.bFitMod method added. Thanks to Lieven Nils Kennes for pointing towards the issue.

DoseFinding 0.9-11 * Mods Introduce fullMod argument to allow specification of full model parameters (again). * calcTDgrad now calculates the analytical gradient for TD optimal designs for the beta model. The previous numerical gradient could get unstable for particular parameter values. Thanks to Tobias Mielke for the calculations! * planMod.Rd, powMCT.Rd More description on what “sigma” is * optDesign, optContr Catch Mods objects with multiple direction attributes properly in these functions.

DoseFinding 0.9-10

• plot.MCPMod In case of no significant model, do not plot anything.
• optContr Bugfix in function constOptC, previous algorithm selected in some situation an incorrect active set (and hence a suboptimal solution), the current implementation uses quadratic programming (hence the new suggested package quadprog).

DoseFinding 0.9-9

• bFitMod.Bayes Stop if starting values lie outside of bounds specified for the prior distribution
• predict.bFitMod Remove incorrect “if” statement (use “effect-curve” not “EffectCurve”)
• fitModels.bndnls now uses narrowed bounds for 1d models again (as in 0.9-5 and earlier), thanks to Tobias Mielke for reporting the three points above.
• optContr now allows for constrained contrasts, i.e. where the contrast coefficients in placebo and active treatment groups are required to have different signs.

DoseFinding 0.9-8

• MCPMod Major changes needed (also in fitMod and MCTtest) to allow for dose/response names different from “dose”, “resp” when a data-frame is specified (the problem existed as MCTtest, fitMod were called from inside MCPMod).
• bFitMod.Bayes Ensure that the starting values for the parameters are within the bounds specified by the prior (if no starting values are specified). Thanks to Tobias Mielke for reporting this.
• bFitMod.bootstrap Remove bug for model = “linear” and placAdj = TRUE. Thanks to Tobias Mielke for reporting this.

DoseFinding 0.9-7

• fitMod ensure that the data set returned with DRMod objects is in the original order (not sorted by dose). Also ensure the right S matrix is used for fitting for type = “general” and unsorted dose, resp.
• MCTtest fixed problems for type = “general” and unsorted dose, resp.
• glycobrom Added glycobrom data set
• planMod Added planning functions for non-linear modelling
• Coded calculations of compositions to be able to remove dependency on the partitions package
• man files: added reference to paper on generalized MCPMod
• plot.DRMod Minor changes to ensure raw means are always inside the plotting region (for plotData = “means”)

DoseFinding 0.9-6

• optDesign Re-named “fmodels” argument to “models”.
• optDesign for solnp if lowbnd and uppbnd are specified now use a feasible starting value (otherwise solnp might get into problems).
• plot.DRMod, plot.MCPMod now use lattice graphics
• powMCT removed bug in case of placAdj = TRUE (thanks to Tobias Mielke for reporting this)
• ess.mcmc minor change to avoid occasional NA’s
• Mods removed class c(“Mods”, “standMod”), now there is only a class “Mods”, this changes the API of MCTtest, optContr and MCPMod function (direction argument no longer needed, as this info is now contained in the “Mods” object).
• neurodeg added the simulated longitudinal dose-finding data set neurodeg
• targN catch incorrect matrix dimension, when in case of only one alternative model
• fitModel.bndnls old version used narrowed bnds for 1-dim model, when a starting value was supplied manually (instead of calculated via optGrid); fixed.
• MCTtest re-name of p-value column to “adj-p”.

DoseFinding 0.9-5

• targN, powN added function targN to evaluate a target function (e.g. power) for different sample sizes (similar to the old powerMM function). powN is a convenience function for multiple contrast tests using the power.
• sampSizeMCT added convenience function for sample size calculation for multiple contrast tests using the power.
• optContr Re-named “weights” argument to “w”

DoseFinding 0.9-4

• TD, ED Fixed bug for model = linInt and placAdj = TRUE
• powMCT Fixed bug for nr(altModels)=1 in case placAdj=TRUE
• Mods Add requirement that placebo dose needs to be included
• print.bFitMod Do not show n.eff for bootstrap samples
• ess.mcmc return NA, if there is just one unique value in chain
• fitMod, MCTtest catch situations, where type = “normal” and placAdj = TRUE
• bFitMod fixed bug for column names of linear model in case of placAdj = TRUE
• MCPMod: Fixed sign error in model selection, when critV was specified

DoseFinding 0.9-3

• fitMod Improvements of efficiency (removed calls to do.call in optLoc)
• MCPMod passes direction argument now also to TD
• optDesign solnp is now the default optimizer
• calcCrit default for arg designCrit in calcCrit changed (to harmonize calcCrit and optDesign)
• bFitMod use fitMod.raw in bFitMod.bootstrap (for efficiency)
• critVal Remove contMat argument (was unused)
• powMCT Allow power calculation for placebo adjusted data

DoseFinding 0.9-1

• Complete re-structuring and tidying up of the package. Main ideas: (i) smoother integration of g-functions (ii) focus on core functionality (iii) more general code/easier extensibility.
• New features: Bayesian dose-response fitting, nicer plots, optimal designs for non-normal responses, …
• Special Thanks to Tobias Mielke for testing of the package and numerous bug reports.
• Previous versions of the source are available under http://cran.r-project.org/package=DoseFinding under “Old sources”, a Windows binary of the last version before the changes is available under http://goo.gl/p1UZ7.

DoseFinding 0.6-3

• Added PACKAGE = “DoseFinding” to “.C” calls

DoseFinding 0.6-2

• calcOptDesign partial rewrite of optDes.c and optDesign.R to fix segfault bug.

DoseFinding 0.6-1

• vcov.gDRMod is now functional, predict.gDRMod now allows calculation of confidence intervals
• gFitDRModel minor changes in underlying optimizer
• explicitly export the gradients of the model functions now

DoseFinding 0.5-7

• gFitDRModel now always returns an estimate (either the best value from nlminb or from the grid search if nlminb fails)
• gMCPtest: use sigma = corMat instead of corr = corMat in p/qmvnorm calls (mvtnorm complained in 1-dimensional case)
• gFitDRModel: Introduced default for bnds argument.
• plot.MCPMod: Plot clinRel in the right place, when direction is equal to “decreasing” (thanks to Jan Rekowski)
• planMM, critVal: When vCov is specified now right correlation matrix is calculated
• calcOptDesign: Additional argument (standDopt) to allow for optional standardization (division of the log determinant by the number of parameters) of the D-optimal design criterion.

DoseFinding 0.5-6

• getGrid corrected bug for Ngrd > 75025
• calcOptDesign: For method = “exact” and n2 > 0 the function did not return the optimal incremental design but the overall optimal design

DoseFinding 0.5-5

• gFitDRModel can now fit dose-response models without intercept
• gMCPtest minor changes to allow for user defined contrast matrix

DoseFinding 0.5-4

• MCPtest now uses correct degrees of freedom if addCovars != ~1
• Feedback from Andreas Krause led to a number smaller changes in the package (e.g., plot.(g)DRMod or fitDRModel). Thanks Andreas!
• Print lattice plots explicitly to increase compability with Sweave.

DoseFinding 0.5-3

• Ensure in rndDesign that N is recognized as an integer by using N <- round(N), to avoid floating point problems.
• Remove naming bug in gFitDRModel (drFit instead of drEst)

DoseFinding 0.5-2

• Corrected bug in b-vector for sigEmax model (calcBvec, only affected MED-type optimal designs)
• Included INDEX file to order the overview help-page better
• predict.DRMod now stops when type = “fullModel” and the argument newdata does not contain values for all variables specified in addCovars (thanks to Mouna).

DoseFinding 0.5-1

• Restructured calcOptDesign function to allow for user defined criteria functions.
• The MCPMod object now always contains a estDose and fm entry (which is NA in case of non-significance or non-convergence)
• Added generalized fitting code, variances and covariances of estimates are not available at the moment.
• Added vCov argument to planMM, sampSize, powerMM (so it is possible to take into account covariances when calculating optimal contrasts)
• Changed order in trellis plots in plotModels (order as specified in models list instead of alphanumerical order)
• Restructured and summarized help pages
• Removed dependency on numDeriv package (only suggested now), this is only needed for calculating optimal designs involving the beta model.

DoseFinding 0.4-3

• Minor change in Makevars file (so that DoseFinding works on Solaris).

DoseFinding 0.4-2

• calcBayesEst, getUpdDesign: Minor changes to make functions more suited for general purpose use.

DoseFinding 0.4-1

• Introduced new functions calcBayesEst and getUpdDesign, both were used for simulation purposes in the paper Bornkamp et al. (2011) “Response Adaptive Dose-Finding under Model Uncertainty” (to appear in Annals of Applied Statistics).

DoseFinding 0.3-1

• calcOptDesign now has an additional optimizer “exact”. This methods calculates all possible designs for a given sample size and then selects the best.
• Changed order in MakeVars as requested
• calcCrit now checks whether there are not less design points than parameters.
• Code now checks for positive sigma in powCalc and powerMM

DoseFinding 0.2-3

• MED function now checks for clinRel > 0 (thanks to Georgina).
• Changed minor bug in output from print.MCPtest (print one-sided just once)
• Code now outputs a warning, when ‘models’ argument is missing (in MCPMod and fullMod function); in fitDRModel it outputs a warning if ‘model’ is missing
• Introduced a default base = 0 and maxEff = 1 for the plotModels function.
• Added a summary method for DRMod objects.
• Removed superfluous addCovarVals argument from predict.DRMod
• Removed option method = “mult” in calcOptDesign

DoseFinding 0.2-2

• calcCrit and calcOptDesign now check for NA, NaN or +-Inf values in the gradient and bvector (and stop execution when these values occur) before passing these values to the C code.
• Introduced a logLik method for DRMod objects
• Changed mvtnorm.control default argument for “interval” to reflect recent changes in mvtnorm package.

DoseFinding 0.2-1

• Made the getGrad function (gradient for dose-response model), including documentation available for end-user (was previously hidden in NAMESPACE)
• Changes in the plot.MCPMod function (col argument for panel.superpose was read in different order depending on lattice options, now there is a manual workaround with panel.xyplot calls for each group)

DoseFinding 0.1-3

• Smaller changes in calcCrit functions (the parameter p is now calculated by the nPars function as in getOptDesign)
• Add further options to powerScenario function (now possible to for user-specified row and column names for output matrix)

DoseFinding 0.1-2

• Removed one example from sampSize to reduce check time.
• modelSelect: Use first model when two models have exactly the same AIC or BIC value.
• predict.DRMod: Return NA as standard deviation if code cannot calculate Cholesky transformation of covariance matrix (thanks to Setia Pramana for the hint).
• calcCrit: Code now allows for specifying multiple designs in a matrix.

DoseFinding 0.1-1

• fitModel.nls now checks whether nls with plinear option made a positive number of iterations (as additional convergence check). In some cases (eg. when number of parameters = number of doses) plinear does not do any iteration and does not put out a warning message that the algorithm failed.
• The calcOptDesign function now allows for upper and lower bounds on the allocation weights.
• There is no longer the need to specify clinRel, when one wants to calculate a D-optimal design.
• Output of bootMCPMod function in case of model averaging now also includes dose estimates under each model & corrected bug in print.bootMCPMod function (thanks to Setia Pramana)

DoseFinding 0.1

• 1st Release as version 0.1. Improvements over MCPMod package:
• Extended and improved version of MCPMod (allowing for covariates and robustified self-developed optimizer)
• Functions for MCP (MCPtest) and Modelling (fitDRModel) part now available to the user
• New functions (eg. bootMCPMod, powerScenario)
• Functions for calculating optimal designs