DoseFinding: Planning and Analyzing Dose Finding Experiments
The DoseFinding package provides functions for the design and analysis of dose-finding experiments (for example pharmaceutical Phase II clinical trials). It provides functions for: multiple contrast tests (MCTtest), fitting non-linear dose-response models (fitMod), a combination of testing and dose-response modelling (MCPMod), and calculating optimal designs (optDesign), both for normal and general response variable. package
The main functions are:
MCTtest : Implements a multiple contrast tests
powMCT : Power calculations for multiple contrast tests
fitMod : Fits non-linear dose-response models
optDesign : Calculates optimal designs for dose-response models
MCPMod : Performs MCPMod methodology
sampSize : General function for sample size calculation
data(IBScovars) ## perform (model based) multiple contrast test ## define candidate dose-response shapes models <- Mods(linear = NULL, emax = 0.2, quadratic = -0.17, doses = c(0, 1, 2, 3, 4)) ## plot models plot(models) ## perform multiple contrast test test <- MCTtest(dose, resp, IBScovars, models=models, addCovars = ~ gender) ## fit non-linear emax dose-response model fitemax <- fitMod(dose, resp, data=IBScovars, model="emax", bnds = c(0.01,5)) ## display fitted dose-effect curve plot(fitemax, CI=TRUE, plotData="meansCI") ## Calculate optimal designs for target dose (TD) estimation doses <- c(0, 10, 25, 50, 100, 150) fmodels <- Mods(linear = NULL, emax = 25, exponential = 85, logistic = c(50, 10.8811), doses = doses, placEff=0, maxEff=0.4) plot(fmodels, plotTD = TRUE, Delta = 0.2) weights <- rep(1/4, 4) desTD <- optDesign(fmodels, weights, Delta=0.2, designCrit="TD")
Bornkamp, B., Bretz, F., Dette, H. and Pinheiro, J. C. (2011). Response-Adaptive Dose-Finding under model uncertainty, Annals of Applied Statistics, 5 , 1611--1631
Bornkamp B., Pinheiro J. C., and Bretz, F. (2009). MCPMod: An R Package for the Design and Analysis of Dose-Finding Studies, Journal of Statistical Software, 29 (7), 1--23
Bretz, F., Pinheiro, J. C., and Branson, M. (2005), Combining multiple comparisons and modeling techniques in dose-response studies, Biometrics, 61 , 738--748
Dette, H., Bretz, F., Pepelyshev, A. and Pinheiro, J. C. (2008). Optimal Designs for Dose Finding Studies, Journal of the American Statisical Association, 103 , 1225--1237
O'Quigley, J., Iasonos, A. and Bornkamp, B. (2017) Handbook of methods for designing, monitoring, and analyzing dose-finding trials, CRC press, Part 3: Dose-Finding Studies in Phase II
Pinheiro, J. C., Bornkamp, B., and Bretz, F. (2006). Design and analysis of dose finding studies combining multiple comparisons and modeling procedures, Journal of Biopharmaceutical Statistics, 16 , 639--656
Pinheiro, J. C., Bornkamp, B., Glimm, E. and Bretz, F. (2014) Model-based dose finding under model uncertainty using general parametric models, Statistics in Medicine, 33 , 1646--1661
Seber, G.A.F. and Wild, C.J. (2003). Nonlinear Regression, Wiley
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Maintainer : Marius Thomas marius.thomas@novartis.com
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