Package ‘randomizeR’

July 23, 2025

Type Package
Title Randomization for Clinical Trials
Version 3.0.2
Maintainer Ralf-Dieter Hilgers <rhilgers@[Link]>
Description This tool enables the user to choose a randomization procedure
based on sound scientific criteria. It comprises the generation of
randomization sequences as well the assessment of randomization procedures
based on carefully selected criteria. Furthermore, 'randomizeR' provides a
function for the comparison of randomization procedures.
License GPL (>= 3)
Encoding UTF-8
Depends R (>= 3.6.0), methods, ggplot2, plotrix, survival, mvtnorm
Imports mstate, purrr, rlang, magrittr, dplyr, coin, PwrGSD, gsDesign,
insight, reshape2
Collate 'getDesign.R' 'randPar.R' 'pbrPar.R' 'rarPar.R' 'randSeq.R'
'rarSeq.R' 'GSD-Bias.R' 'abcdPar.R' 'abcdSeq.R'
'getParameters.R' 'getExpectation.R' 'survEndp.R' 'expEndp.R'
'normEndp.R' 'endpoint.R' 'util.R' 'getStat.R' 'power.R'
'imbalance.R' 'corGuess.R' 'logRankDistribution.R' 'doublyF.R'
'testDec.R' 'doublyT.R' 'chronBias.R' 'selBias.R' 'bias.R'
'issue.R' 'assess.R' 'bbcdPar.R' 'bbcdSeq.R' 'ebcPar.R'
'bsdPar.R' 'bsdSeq.R' 'chenPar.R' 'chenSeq.R'
'chronBiasStepT.R' 'combinedBias.R' 'compare.R' 'crPar.R'
'crSeq.R' 'createParam.R' 'derFunc.R' 'desFunc.R'
'getDesFunc.R' 'derringerLs.R' 'derringerRs.R' 'derringerTs.R'
'desScores.R' 'desirability.R' 'ebcSeq.R' 'evaluate.R'
'gbcdPar.R' 'gbcdSeq.R' 'hadaPar.R' 'hadaSeq.R' 'maccombo.R'
'mpPar.R' 'mpSeq.R' 'pbrSeq.R' 'probUnDes.R' 'rtbdSeq.R'
'rpbrSeq.R' 'randomBlockSeq.R' 'randomizeROverview.R'
'randomizeRPackage.R' 'rpbrPar.R' 'tbdPar.R' 'rtbdPar.R'
'saveAssess.R' 'saveRand.R' 'stratifiedAnalysis.R' 'tbdSeq.R'
'udPar.R' 'udSeq.R'
Suggests testthat, knitr

1
2 Contents

RoxygenNote 7.2.3
NeedsCompilation no
Author David Schindler [aut],
Diane Uschner [aut],
Denis Razsolkov [ctb],
Dimitar Mihaylov [ctb],
Marcia Viviane Rueckbeil [ctb],
Martin Manolov [ctb],
Thi Mui Pham [ctb],
Michael Martini [ctb],
Ralf-Dieter Hilgers [aut, ths, cre],
Nicole Heussen [aut, ths],
Daniel Bodden [ctb]
Repository CRAN
Date/Publication 2023-09-18 19:50:02 UTC

Contents
randomizeR-package . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4
a . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 5
abcdPar . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 5
analyse . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 6
assess . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 7
bbcdPar . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 8
blocks . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 9
bsdPar . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 10
chenPar . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 11
chronBias . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 12
coin . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 13
combineBias . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 14
compare . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 15
corGuess . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 16
createParam . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 17
createSeq . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 18
crPar . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 18
derFunc . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 19
desirability . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 20
ebcPar . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 21
evaluate . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 22
expEndp . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 24
gbcdPar . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 25
generateAllSequences . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 26
generateRandomSequences . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 28
genNcps_new . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 33
getCorGuesses . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 33
getDesFunc . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 34
Contents 3

getDesign . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 34
getDesScores . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 37
getDistributionPars . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 38
getExpectation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 39
getProbabilities . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 41
getRandomizationList . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 42
get_p_values_new . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 43
GSD_allocation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 44
GSD_allocation_seq . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 45
hadaPar . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 46
imbal . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 47
issue . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 48
K . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 49
lambda . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 49
method . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 50
mpPar . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 50
mti . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 51
mu . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 51
N . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 52
normEndp . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 52
overview . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 53
pbrPar . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 55
plot . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 56
plotDes . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 57
plotEv . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 58
plotSeq . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 59
probUnDes . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 59
randBlocks . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 61
randPar . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 61
randSeq-class . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 62
rarPar . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 62
ratio . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 63
rho . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 64
rpbrPar . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 64
rtbdPar . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 65
saveAssess . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 66
saveRand . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 67
scale . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 67
seed . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 68
selBias . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 68
setPower . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 70
shape . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 71
sigma . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 71
summary . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 71
survEndp . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 73
tbdPar . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 74
TV . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 74
type . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 75
4 randomizeR-package

udPar . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 75

Index 77

randomizeR-package Randomization for Clinical Trials

Description
This tool enables the user to choose a randomization procedure based on sound scientific criteria.
It comprises the generation of randomization sequences as well the assessment of randomization
procedures based on carefully selected criteria. Furthermore, randomizeR provides a function for
the comparison of randomization procedures.

Acknowledgement
This research is embedded in the IDeAl project, which has received funding from the European
Union’s Seventh Framework Programme for research, technological development and demonstra-
tion under Grant Agreement no 602552.

Author(s)
David Schindler <[Link]@[Link]>, Diane Uschner <[Link]@[Link]>, Ralf-
Dieter Hilgers, Nicole Heussen, Marcia Viviane Rueckbeil <[Link]@[Link]>

References
W. F. Rosenberger and J. M. Lachin (2002) Randomization in Clinical Trials. Wiley.
#’ D. Uschner, D. Schindler, R. D. Hilgers and N. Heussen (2018). "randomizeR: An R Package
for the Assessment and Implementation of Randomization in Clinical Trials." Journal of Statistical
Software, 85(8), pp. 1-22. doi: 10.18637/jss.v085.i08 .
D. Schindler (2016) Assessment of Randomization Procedures in the Presence of Selection and
Chronological Bias. PhD Thesis.
D. Uschner, R. D. Hilgers, N. Heussen (2018). "The impact of selection bias in randomized multi-
arm parallel group clinical trials." PLOS ONE, 13(1): e0192065. doi: 10.1371/[Link].0192065.
M. V. Rueckbeil, R. D. Hilgers, N. Heussen (2019). "Randomization in survival studies: An evalua-
tion method that takes into account selection and chronological bias." PLOS ONE, 14(6): e0217946.
doi: 10.1371/[Link].0217946.

See Also
For functionality for randomization procedures, see randPar and genSeq. For the criteria for the
assessment of randomization procedures, see issues. For the assessment and comparison of ran-
domization procedures, see assess and compare.
a 5

a Function returning the adjusting parameter a slot of an S4 object

Description
Function returning the adjusting parameter a slot of an S4 object

Usage
a(obj)

Arguments
obj object of class randPar

Value
the value of the adjusting parameter a of an S4 object

abcdPar Representing Accelerated Biased Coin Design

Description
Represents the randomization procedure Accelerated Biased Coin Design.

Usage
abcdPar(N, a, groups = LETTERS[1:2])

Arguments
N integer for the total sample size of the trial.
a nonnegative parameter which controls the degree of randomness: For decreasing
a the allocations become deterministic, while for increasing a the randomization
procedure tends to complete randomization.
groups character vector of labels for the different treatments.

Details
This is a class of ’biased coins’ where the probability of selecting the under-represented treatment
is dependent from the absolute difference between the two treatment allocations up to the current
step.
6 analyse

Value
S4 object of the class abcdPar.

References
A. B. Antognini and A. Giovagnoli (2004) A new ’biased coin design’ for the sequential allocation
of two treatments. Journal of the Royal Statistical Society. Series C (Applied Statistics) 53, No. 4,
651-664

See Also
Other randomization procedures: bbcdPar, bsdPar, chenPar, crPar, createParam(), ebcPar,
gbcdPar, hadaPar, mpPar, pbrPar, rarPar, rpbrPar, rtbdPar, tbdPar, udPar

analyse Creates stratified sequences Compares stratified sequences to their re-

spective non-stratified version under the influence of bias.

Description
Creates stratified sequences Compares stratified sequences to their respective non-stratified version
under the influence of bias.

Arguments
endp object of class endpoint.
pr at least one object of class randPar or just a list of objects of class randPar

Details
Stratified and Non-stratified versions of a randomization sequence behave differently with respect
to issues like selection bias, chronological bias or combined bias. The analyse function creates
both versions of a sequence for each of the specified randomization procedures and analyses them
in relation to the bias created according to the theta and eta values. The first argument should
specify the total sample size of patients. The second argument should be one of class normEndp
describing a normally distributed endpoint. The third argument should be the allocation ratio for
the different strata. The fourth argument should be the number of strata in the clinical trial. The fifth
and sixth arguments should be the selection bias effect eta and the time trend theta. The seventh
argument should be a vector of strings representing different randomization procedures. The strings
should be given as described by the getDesign function. Any additional parameters should be
given after the design name of the procedure encapsulated in parenthesis.

Value
The function returns a matrix that summarizes the performance of the randomization procedures.
The values for each randomization procedure represent the percentage of sequences that kept the 5
assess 7

assess Assessing randomization sequences

Description

Assesses randomization sequences based on specified issues in clinical trials.

Usage

assess(randSeq, ..., endp)

## S4 method for signature 'randSeq,missing'

assess(randSeq, ..., endp)

## S4 method for signature 'randSeq,endpoint'

assess(randSeq, ..., endp)

Arguments

randSeq object of class randSeq.

... at least one object of class issue or just a list of objects of the class issue.
endp object of class endpoint, or missing.

Details

Randomization sequences behave differently with respect to issues like selection bias, chronological
bias, or loss in power estimation. The assess function evaluates the behavior of randomization
sequences with respect to these issues. The first argument should be a result of one of the functions
genSeq or getAllSeq. The second argument should be any number of issues arising in a clinical
trial. The last argument endp may be provided if the assessment should take the distribution of the
treatment groups into account, e.g. for power evaluation.

Value

S4 object of class assessment summarizing the assessment of the randomization procedure.

See Also

Representation of randomization procedures: randPar

Generation of randomization sequences: genSeq
issues for the assessment of randomization sequences
8 bbcdPar

Examples
# assess the full set of Random Allocation Rule for N=4 patients
sequences <- getAllSeq(rarPar(4))
issue1 <- corGuess("CS")
issue2 <- corGuess("DS")
issue3 <- imbal("imb")
issue4 <- imbal("maxImb")
assess(sequences, issue1, issue2, issue3, issue4)

# assess one sequence of the Big Stick Design with respect to correct guesses
sequence <- genSeq(bsdPar(10, 2), seed = 1909)
assess(sequence, issue1)

# assess the same sequence with respect to selection bias and power for a normal endpoint
endp <- normEndp(c(2, 2), c(1, 1))
issue5 <- selBias("CS", 4, "exact")
issue6 <- setPower(2, "exact")
assess(sequence, issue1, issue5, issue6, endp = endp)

# assess the same sequence with respect to selection bias for an exponential endpoint
endp <- expEndp(lambda = c(0.5, 0.5), cenRate=0.1, accrualTime=1, cenTime=5)
issue7 <- selBias("CS", 0.1, "exact")
assess(sequence, issue1, issue7, endp = endp)

# recommended plot for the assessment of rejection probabilities

RP <- getAllSeq(crPar(6))
cB <- chronBias(type = "linT", theta = 1/6, method = "exact")
sB <- selBias(type= "CS", eta = 1/4, method = "exact")
normEndp <- normEndp(c(0, 0), c(1, 1))
A <- assess(RP, cB, sB, endp = normEndp)
D <- A$D
desiredSeq <- round(sum(D[,2][D[,3] <= 0.05 & D[,4] <= 0.05]), digits = 4)
colnames(D) <- c("Seq", "Prob", "SB", "linT")
g <- ggplot(D, aes(x = SB, y = linT))
g <- g + annotate("rect", xmin = 0, xmax = 0.05, ymin = 0, ymax = 0.05,
alpha=0.2, fill="green")
g <- g + geom_point(alpha = 1/10, size = 3, col = "orange")
g <- g <- g + geom_vline(xintercept = 0.05, col = "red")
g <- g + geom_hline(yintercept = 0.05, col = "red")
g <- g + geom_text(data = NULL, x = 0, y = 0,
label = paste("Proportion:", desiredSeq), hjust=0, vjust=0, size = 7)
g

bbcdPar Representing Bayesian Biased Coin Design

Description
Represents the randomization procedure Bayesian Biased Coin Design.
blocks 9

Usage
bbcdPar(N, a, groups = LETTERS[1:2])

Arguments
N integer for the total sample size of the trial.
a nonnegative parameter which controls the degree of randomness: For decreasing
a the allocations become deterministic, while for increasing a the randomization
procedure tends to complete randomization.
groups character vector of labels for the different treatments.

Details
Extension of Efron’s biased coin design.

Value
S4 object of the class bbcdPar.

References
A. B. Antognini and Maroussa Zagoraiou (2014) Balance and randomness in sequential clinical
trials: the dominant biased coin design. Pharmaceutical Statistics 13(2), 119-127

See Also
Other randomization procedures: abcdPar, bsdPar, chenPar, crPar, createParam(), ebcPar,
gbcdPar, hadaPar, mpPar, pbrPar, rarPar, rpbrPar, rtbdPar, tbdPar, udPar

blocks Function returning the block slot of an S4 object

Description
Function returning the block slot of an S4 object

Usage
blocks(obj)

Arguments
obj object of class pbrPar

Value
a vector with the lenghts of each block of a pbrPar object
10 bsdPar

bsdPar Representing Big Stick Design

Description

Represents the randomization procedure Big Stick Design.

Usage

bsdPar(N, mti, groups = LETTERS[1:2])

Arguments

N integer for the total sample size of the trial.

mti maximum tolerated imbalance in patient numbers during the trial.
groups character vector of labels for the different treatments.

Details

Tossing a fair coin as long as the difference in group sizes does not exceed the mti. If the mti is
reached a deterministic allocation is done, so that the difference in group sizes is reduced.

Value

S4 object of the class bsdPar.

References

J. F. Soares and C. F. Jeff Wu (1983) Some Restricted Randomization Rules in Sequential Designs.
Comm. in Stat., 12, 2017-34.

See Also

Other randomization procedures: abcdPar, bbcdPar, chenPar, crPar, createParam(), ebcPar,

gbcdPar, hadaPar, mpPar, pbrPar, rarPar, rpbrPar, rtbdPar, tbdPar, udPar
chenPar 11

chenPar Representing Chen’s Design

Description

Represents the randomization procedure Chen’s Design.

Usage

chenPar(N, mti = N, p = 0.5, groups = LETTERS[1:2])

Arguments

N integer for the total sample size of the trial.

mti maximum tolerated imbalance in patient numbers during the trial.
p success probability of the biased coin (e.g. in Efron’s Biased Coin Design).
groups character vector of labels for the different treatments.

Details

Flip a biased coin with probability p in favor of the treatment which is allocated less frequently as
long as the difference in group sizes does not exceed the mti. If the mti is reached a deterministic
allocation is done, so that the difference in group sizes is reduced. If both treatments have been
assigned equally often a fair coin is tossed.

Value

S4 object of the class chenPar.

References

Chen Yung-Pin (1999) Biased coin design with imbalance tolerance. Comm. in Stat., 15, 953-975.

See Also

Other randomization procedures: abcdPar, bbcdPar, bsdPar, crPar, createParam(), ebcPar,

gbcdPar, hadaPar, mpPar, pbrPar, rarPar, rpbrPar, rtbdPar, tbdPar, udPar
12 chronBias

chronBias Representing chronological bias

Description
Represents the issue of chronological bias in a clinical trial.

Usage
chronBias(type, theta, method, saltus, alpha = 0.05)

Arguments
type character string, should be one of "linT", "logT", or "stepT", see Details.
theta factor of the time trend for further details see type.
method character string, should be one of "sim" or "exact", see Description.
saltus integer or missing specifying the patient index (i.e. position) of the step in case
of step time trend.
alpha significance level

Details
Chronological bias can be an issue in the design of a clinical trial. The chronBias function is a
constructor function for an S4 object of the class chronBias representing the issue of chronolog-
ical bias, s.a. time trends, in a clinical trial. It supports two possible modes, method="sim" and
method="exact", and three different types of trend.
If method="sim", the object represents the simulated type-I-error rate given the level alpha, the
selection effect eta and the biasing strategy type. When calling assess for a chronBias object
with method="sim", one test decision is computed for each sequence of randSeq. The type-I-error
rate (power) is the proportion of falsely (correctly) rejected null hypotheses.
If method="exact", the object represents the exact type-I-error probability given the level alpha,
the selection effect eta and the biasing strategy type. When calling assess for a chronBias object
with method="exact", the p-value of each randomization sequence is computed. For normal end-
points and two treatment groups these p-values are exact values which can be calculated from the
sum of the corresponding quantiles of the doubly noncentral t-distribution. For more than two treat-
ment groups, exact p-values are computed using a doubly noncentral F distribution. For exponential
endpoints the p-values are obtained using an approximation formula.

Types of chronological bias:

type = "linT" Represents linear time trend. Linear time trend means that the time trend function
of the patients, i.e. expected response for normal endpoints, increases evenly by theta/(N-1)
with every patient included in the study, until reaching theta after N patients. Linear time
trend may occur as a result of gradually relaxing in- or exclusion criteria throughout the trial.
It can be represented by the formula:

f (i) = (i − 1)/(N − 1)θ

coin 13

type = "logT" Represents logarithmic time trend. Logarithmic time trend means that the time
trend function of the patients, i.e. expected response for normal endpoints, increases logarith-
mically in the patient index by theta/log(N) with every patient included in the study, until
reaching theta after N patients. Logarithmic time trend may occur as a result of a learning
curve, i.e. in a surgical trial. It can be represented by the formula:

log(i)/ log(N )θ

type = "stepT" Represents step trend. Step trend means that the expected response of the pa-
tients increases by theta after a given point ("saltus") in the allocation process. Step trend
may occur if a new device is used after the point c = "saltus", or if the medical personal
changes after this point. Step time trend can be represented by the formula:

f (i) = 1c<i≤N θ

Value
S4 object of class chronBias, a formal representation of the issue of chronological bias in a clinical
trial.

References
G. K. Rosenkranz (2011) The impact of randomization on the analysis of clinical trials. Statistics
in Medicine, 30, 3475-87.
M. Tamm and R.-D. Hilgers (2014) Chronological bias in randomized clinical trials under different
types of unobserved time trends. Methods of Information in Medicine, 53, 501-10.

See Also
Other issues: combineBias(), corGuess, imbal, issue, selBias, setPower()

Examples
# create a linear time trend with theta = 0.5 for which the exact rejection probabilities
# are calculated
cbias <- chronBias("linT", 0.5, "exact")

# create a stepwise time trend with theta = 1 after 10 allocations for which the test
# decision is simulated
cbias <- chronBias("stepT", 1, "sim", 10)

coin Function returning the coin slot of an S4 object

Description
Function returning the coin slot of an S4 object
14 combineBias

Usage
coin(obj)

Arguments
obj object extending class randPar or randSeq

Value
The success probability of the biased coin

combineBias Combined bias criterion

Description
This class combines a selBias object and a chronBias object to a new object. In the analysis
within the new object the two types of bias are treated as additive effect for normal endpoints and
as multiplicative effect for exponential endpoints.

Usage
combineBias(selBias, chronBias)

Arguments
selBias object of class selBias
chronBias object of class chronBias

Value
A combined bias object that combines a selBias and a chronBias object

See Also
Other issues: chronBias, corGuess, imbal, issue, selBias, setPower()

Examples
chronBias <- chronBias(type="linT", theta=1, method="sim")
selBias <- selBias(type="CS", eta=1, method="sim")
combineBias(selBias, chronBias)
compare 15

compare Comparison of randomization procedures

Description

Compares randomization procedures based on a specified issue in clinical trials.

Usage

compare(issue, ..., endp)

## S4 method for signature 'issue,missing'

compare(issue, ..., endp)

## S4 method for signature 'issue,endpoint'

compare(issue, ..., endp)

Arguments

issue object of class issue.

... at least one object of class randSeq or a list of objects of class randSeq.
endp object of class endpoint, or missing.

Details

Randomization procedures behave differently with respect to issues like selection bias, chronologi-
cal bias, or loss in power estimation. The compare function evaluates the behavior of randomization
procedures with respect to one issue. Its first argument should represent one of the implemented
issues. The second argument should be any number of objects of the class randSeq. These objects
represent the randomization procedures for the planned comparison. The last argument endp may
be provided if the assessment should take the distribution of the treatment groups into account, e.g.
for power evaluation.

Value

S4 object of class comparison summarizing the comparison of the randomization procedures.

See Also

Representation of randomization procedures: randPar

Generation of randomization sequences: genSeq
issues for the assessment of randomization sequences
16 corGuess

Examples
# compare Random Allocation Rule and Big Stick for N = 4 with respect to
# correct guesses
RAR <- getAllSeq(rarPar(4))
BSD <- getAllSeq(bsdPar(4, mti = 2))
corGuess <- corGuess("CS")
(comp <- compare(corGuess, RAR, BSD))
plot(comp)

# compare the same procedures with respect to selection bias for a normal endpoint
endp <- normEndp(c(2, 2), c(1, 1))
selBias <- selBias("CS", 4, "exact")
(comp <- compare(selBias, RAR, BSD, endp = endp))
plot(comp)

# compare the same procedures with respect to selection bias for an exponential endpoint
endp <- expEndp(lambda = c(0.5, 0.5), cenRate=0.1, accrualTime=1, cenTime=5)
selBias <- selBias("CS", 0.1, "exact")
(comp <- compare(selBias, RAR, BSD, endp = endp))
plot(comp)

corGuess Representing the expected number of correct guesses

Description
Represents the expected number of correct guesses of randomization sequences.

Usage
corGuess(type)

Arguments
type character string, should be one of "CS" or "DS", see Details.

Details
Selection bias can be an issue in the design of a clinical trial. The expected number of correct
guesses is one measure for selection bias. The corGuess function is a constructor function for an
S4 object of the class corGuess representing the issue of correct guesses in a clinical trial. The
parameter type takes the following values:

"CS" refers to "convergence strategy", i.e. the investigator predicts the treatment which has hitherto
occurred less often.
"DS" refers to "divergence strategy", i.e. the investigator predicts the treatment which has hitherto
occurred more often.
createParam 17

Value
S4 object of class corGuess, a formal representation of the issue of correct guesses in a clinical
trial.

References
D. Blackwell and J.L. Hodges Jr. (1957) Design for the control of selection bias. Annals of Mathe-
matical Statistics, 25, 449-60.

See Also
Other issues: chronBias, combineBias(), imbal, issue, selBias, setPower()

createParam Representing any randomization procedure

Description
Represents any randomization procedure for a two-armed clinical trial.

Usage
createParam(method, N, mti, bc, rb, p, ini, add, filledBlock)

Arguments
method method that is used to generate the (random) allocation sequence. It can take
values PBR, RAR, HAD, PWR, EBC, BSD, CR, TBD, UD, and MP.
N integer for the total sample size of the trial.
mti maximum tolerated imbalance in patient numbers during the trial.
bc vector which contains the lengths k_1,...,k_l of each block. This means that
the vector bc will have one entry for each block.
rb block lengths of the blocks that can be selected equiprobable at random.
p success probability of the biased coin (e.g. in Efron’s Biased Coin Design).
ini integer representing the initial urn composition.
add integer representing the number of balls that are added to the urn in each step.
filledBlock logical whether the last block should be filled or not.

Details
Depending on the input of the user, createParam creates an object representing a randomization
procedures for a two-armed clinical trial (see also randPar).

Value
S4object of the corresponding randomization procedure class.
18 crPar

See Also
Other randomization procedures: abcdPar, bbcdPar, bsdPar, chenPar, crPar, ebcPar, gbcdPar,
hadaPar, mpPar, pbrPar, rarPar, rpbrPar, rtbdPar, tbdPar, udPar

createSeq Query to create a randomization sequence of a particular randomiza-

tion procedure

Description
This function is a query to create an corresponding randomization sequence for a two-armed clinical
trial. If file is defined, the generated sequence is automatically saved to the corresponding path.

Usage
createSeq(file)

Arguments
file A connection, or a character string naming the file to write to.

Value
an object Param, which is available

crPar Representing Complete Randomization

Description
Represents the randomization procedure Complete Randomization.

Usage
crPar(N, K = 2, ratio = rep(1, K), groups = LETTERS[1:K])

Arguments
N integer for the total sample size of the trial.
K number of treatment groups (e.g. K=2 if we compare one experimental against
one control treatment).
ratio vector of length K. The total sample number N and all used block lengths (bc)
have to be divisible by sum(ratio).
groups character vector of labels for the different treatments.
derFunc 19

Details
Toss a fair coin N times in case K=2 and assign the treatments according to the result of the coin. In
case of K>2, replace the coin by a die with K sides.

Value
S4 object of the class crPar.

References
W. F. Rosenberger and J. M. Lachin (2002) Randomization in Clinical Trials. Wiley.

See Also
Other randomization procedures: abcdPar, bbcdPar, bsdPar, chenPar, createParam(), ebcPar,
gbcdPar, hadaPar, mpPar, pbrPar, rarPar, rpbrPar, rtbdPar, tbdPar, udPar

derFunc Representing Derringer-Suich desirability functions

Description
Represents the Derringer-Suich desirability approach.

Usage
derFunc(TV, SLs, b)

Arguments
TV numeric specifying the optimal desired value called the target value.
SLs numeric vector of length at most 2 specifying the lower and/or upper specified
border.
b numeric vector of length at most 2 specifying the weight(s) for the punishment
of deviations from the target value.

Details
derFunc represents the framework for left, right and two-sided desirability functions introduced by
Derringer and Suich (1980). For all three different kinds of desirability functions the parameter
TV must be specified. If the parameter SLs has length 1, either the left- or right-sided desirability
function is created depending from whether the value is smaller (left-sided) or greater (right-sided)
than the target value. By specifying SLs as a vector of length 2 a two-sided desirability function
is created where the lower specified border is determined as the smaller value of SLs and thus the
upper specified border is determined as the greater value. If there are no values specified for the
weights, then they are automatically set to 1 (linear loss).
20 desirability

Value
S4 object of class derFunc, a formal representation of desirability functions introduced by Derringer
and Suich.

References
Derringer, G., and Suich, R., (1980) Simultaneous Optimization of Several Response Variables.
Journal of Quality Technology, 12, 214-219.

See Also
Other desirability topics: evaluate(), getDesScores(), plotDes(), plotEv(), probUnDes()

Examples
# create an object of a left-sided desirability function
dLeft <- derFunc(0.5, 0.3, 2)

# create an object of a right-sided desirability function

dRight <- derFunc(0.5, 0.8, 1)

# create an object of a two-sided desirability function

dLR <- derFunc(0.5, c(0.3, 0.9), c(3, 1))

desirability Desirability functions within the scope of clinical trials

Description
Illustrates the interplay between functions related to desirability indices.

Details
Currently, randomizeR encompasses the class of desirability functions introduced by Derringer and
Suich (1980) and corresponding functions to evaluate and compare randomization sequences which
have been assessed on the basis of desirability indices of specific issues:
• derFunc represents the class of desirability functions according to Derringer-Suich (1980).
• getDesScores can be applied to an object of class assessment together with prespecified
desirability functions to compare the behavior of randomization sequences (on a common
scale \[0,1\]).
• plotDes plots a desScores object on a radar chart.
• evaluate performs a comparison of sequences from different randomization sequences on the
basis of object of the class desScores.
• plotEv plots an evaluation object on a radar chart.
• probUnDes computes the probability of undesired randomization sequences with respect to
certain issues and desirability functions.
ebcPar 21

Examples
# perform a comparison of randomization sequences from different randomization procedures
# with the help of desirability functions

issue1 <- corGuess("CS")

issue2 <- chronBias(type = "linT", theta = 1/4, method = "exact")
RAR <- getAllSeq(rarPar(4))
BSD <- getAllSeq(bsdPar(4, mti = 2))
A1 <- assess(RAR, issue1, issue2, endp = normEndp(c(0,0), c(1,1)))
A2 <- assess(BSD, issue1, issue2, endp = normEndp(c(0,0), c(1,1)))

d1 <- derFunc(TV = 0.5, 0.75, 2)

d2 <- derFunc(0.05, c(0, 0.1), c(1, 1))

# apply the getDesScores function to the assessment output with the specified desirability
# functions to evaluate the behaviour of randomization sequences on a [0,1] scale

DesScore <- getDesScores(A1, d1, d2, weights = c(5/6, 1/6))

DesScore2 <- getDesScores(A2, d1, d2, weights = c(5/6, 1/6))

# plotting the desScores objects

plotDes(DesScore, quantiles = TRUE)
plotDes(DesScore2, quantiles = TRUE)

# summarize the results of getDesScore with respect to the statistic "mean"

evaluate(DesScore, DesScore2)

# plot the evaluation objects for a visualized comparison

plotEv(evaluate(DesScore, DesScore2))

# display which randomzation procedure produces more undesired randomization sequences

# with respect to certain issues and desirability functions
probUnDes(DesScore)
probUnDes(DesScore2)

ebcPar Representing Efron’s Biased Coin Design

Description

Represents the randomization procedure Efron’s Biased Coin Design.

Usage

ebcPar(N, p, groups = LETTERS[1:2])

22 evaluate

Arguments
N integer for the total sample size of the trial.
p success probability of the biased coin (e.g. in Efron’s Biased Coin Design).
groups character vector of labels for the different treatments.

Details
Flip a biased coin with probability p in favor of the treatment which is allocated less frequently. If
both treatments have been assigned equally often a fair coin is tossed.

Value
S4 object of the class ebcPar.

References
B. Efron (1971) Forcing a sequential experiment to be balanced. Biometrika, 58, 403-17.

See Also
Other randomization procedures: abcdPar, bbcdPar, bsdPar, chenPar, crPar, createParam(),
gbcdPar, hadaPar, mpPar, pbrPar, rarPar, rpbrPar, rtbdPar, tbdPar, udPar

evaluate Evaluation of several randomization procedures with respect to cer-

tain desirability functions applied to specified issues.

Description
Evaluation of several randomization procedures with respect to certain desirability functions applied
to specified issues.

Usage
evaluate(..., statistic)

## S4 method for signature 'missing'

evaluate(..., statistic)

## S4 method for signature 'character'

evaluate(..., statistic)

Arguments
... at least one object of the class desScores or a list of objects of the class desScores.
statistic character string that specifies on the basis of which statistic the evaluate func-
tion should be applied. The statistic can be chosen from "mean", "median",
"min" or "max".
evaluate 23

Details

The evaluate function allows the user to compare and evaluate different randomization procedures.
It expects a number of objects that result when applying the getDesScores function to an assess
object and specified desirability functions. The evaluate function summarizes the desirability
scores of each randomization procedure on the basis of a prespecified statistic and incorporates
them into a data frame. If no statistic is specified then it is automatically set to mean. If the function
is applied to only one object it corresponds simply to summary(getDesScores(...)).

Value

S4 object of class evaluation Comparison of randomization procedures with respect to desirability

functions applied to specified issues, summarized by a prespecified statistic.

References

D. Schindler Assessment of Randomization Procedures in the Presence of Selection and Chrono-

logical Bias. PhD Thesis.

See Also

Representation of randomization procedures: randPar

Generation of randomization sequences: genSeq
issues for the desirability of randomization sequences
Other desirability topics: derFunc, getDesScores(), plotDes(), plotEv(), probUnDes()

Examples
# compare Random Allocation Rule to Big Stick Design with respect to different issues
# and their corresponding desirability functions
issue1 <- corGuess("CS")
issue2 <- corGuess("DS")
RAR <- getAllSeq(rarPar(4))
BSD <- getAllSeq(bsdPar(4, mti = 2))
A1 <- assess(RAR, issue1, issue2)
A2 <- assess(BSD, issue1, issue2)

d1 <- derFunc(TV = 0.1, 0.7, 2)

d2 <- derFunc(0.5, c(0.3, 0.8), c(1, 1))
DesScore <- getDesScores(A1, d1, d2, weights = c(5/6, 1/6))
DesScore2 <- getDesScores(A2, d1, d2, weights = c(5/6, 1/6))

evaluate(DesScore, DesScore2)
evaluate(DesScore, DesScore2, statistic = "max")
24 expEndp

expEndp Representation of exponentially distributed endpoints

Description

Represents exponentially distributed endpoints in clinical trials.

Usage

expEndp(lambda, cenRate, accrualTime = 0, cenTime)

Arguments

lambda vector of the exponential rate parameters in each treatment group.

cenRate exponential censoring rate in a survival study.
accrualTime duration of the accrual period in a survival study.
cenTime total duration of a survival study (maximum length of followup).

Details

The expEnd function is a constructor function for an S4 object of the class expEnd representing
an exponentially distributed endpoint in a clinical trial. In conjunction with the assess function,
exponential endpoints admit the calculation of the ’exact’ type-I-error probability and power using
an approximation formula.

Value

A S4 object representing an exponentially distributed endpoint in a clinical trial.

See Also

Compute exact or simulated type-I-error: assess.

Other endpoint types: normEndp, survEndp

Examples
# set the parameters of two exponentially distributed endpoints
endp <- expEndp(lambda = c(1, 2), cenTime = 10, cenRate = 0.01)
gbcdPar 25

gbcdPar Representing Generalized Biased Coin Design

Description

Represents the randomization procedure Generalized Biased Coin Design.

Usage

gbcdPar(N, rho, groups = LETTERS[1:2])

Arguments

N integer for the total sample size of the trial.

rho nonnegative parameter which my be adjusted according to how strongly it is
desired to balance the experiment. If rho = 1, we have Wei’s urn design with
alpha = 0. If rho = 0, we have complete randomization.
groups character vector of labels for the different treatments.

Details

Generalization of Wei’s urn and Efron’s biased coin design.

Value

S4 object of the class gbcdPar.

References

R. L. Smith (1984) Sequential treatment allocation using biased coin designs. Journal of the Royal
Statistical Society B, 46, 519-543.
W. F. Rosenberger and J. M. Lachin (2002) Randomization in Clinical Trials. Wiley, 64-65

See Also

Other randomization procedures: abcdPar, bbcdPar, bsdPar, chenPar, crPar, createParam(),

ebcPar, hadaPar, mpPar, pbrPar, rarPar, rpbrPar, rtbdPar, tbdPar, udPar
26 generateAllSequences

generateAllSequences Complete set of randomization sequences

Description
Computes all randomization sequences for the given randomization procedure, and stores them in
an object along with the parameters belonging to the randomization procedure.

Usage
getAllSeq(obj)

## S4 method for signature 'pbrPar'

getAllSeq(obj)

## S4 method for signature 'rarPar'

getAllSeq(obj)

## S4 method for signature 'abcdPar'

getAllSeq(obj)

## S4 method for signature 'bbcdPar'

getAllSeq(obj)

## S4 method for signature 'ebcPar'

getAllSeq(obj)

## S4 method for signature 'bsdPar'

getAllSeq(obj)

## S4 method for signature 'chenPar'

getAllSeq(obj)

## S4 method for signature 'crPar'

getAllSeq(obj)

## S4 method for signature 'gbcdPar'

getAllSeq(obj)

## S4 method for signature 'hadaPar'

getAllSeq(obj)

## S4 method for signature 'mpPar'

getAllSeq(obj)

## S4 method for signature 'tbdPar'

getAllSeq(obj)
generateAllSequences 27

## S4 method for signature 'udPar'

getAllSeq(obj)

Arguments

obj object specifying the randomization procedure, see randPar or createParam.

Details

getAllSeq is a generic function which dispatches different methods depending on the type of input.
The set of sequences of a procedure is computed by enumerating all possible sequences and elimi-
nating those that are not possible in the randomization procedure specified by obj. The parameters
of the randomization procedure are saved along with the sequences to ensure reproducibility of the
results.

Value

An object inheriting from randSeq, representing the set of randomization sequences for the given
parameters. The output consists of the parameters used for the generation of the randomization
sequences (see createParam) and the matrix M that stores the randomization sequences in its rows.

See Also

createParam

Examples

# all randomization sequences of Efron's Biased Coin Design with p = 0.667 for N = 6
myPar <- ebcPar(6, 0.667)
getAllSeq(myPar)

# all randomization sequences of Big Stick Design with mti = 2 for N = 6

myPar <- bsdPar(6, 2)
getAllSeq(myPar)

# all randomization sequences of Permuted Block Randomization with block sizes 4 and 2
myPar <- pbrPar(c(4, 2))
getAllSeq(myPar)
28 generateRandomSequences

generateRandomSequences
Generate random sequences

Description
Generates randomization sequences from a given randomization procedure.

Usage
genSeq(obj, r, seed)

## S4 method for signature 'pbrPar,missing,numeric'

genSeq(obj, r, seed)

## S4 method for signature 'pbrPar,numeric,numeric'

genSeq(obj, r, seed)

## S4 method for signature 'pbrPar,missing,missing'

genSeq(obj, r, seed)

## S4 method for signature 'pbrPar,numeric,missing'

genSeq(obj, r, seed)

## S4 method for signature 'rarPar,numeric,numeric'

genSeq(obj, r, seed)

## S4 method for signature 'rarPar,missing,numeric'

genSeq(obj, r, seed)

## S4 method for signature 'rarPar,numeric,missing'

genSeq(obj, r, seed)

## S4 method for signature 'rarPar,missing,missing'

genSeq(obj, r, seed)

## S4 method for signature 'abcdPar,numeric,numeric'

genSeq(obj, r, seed)

## S4 method for signature 'abcdPar,numeric,missing'

genSeq(obj, r, seed)

## S4 method for signature 'abcdPar,missing,numeric'

genSeq(obj, r, seed)

## S4 method for signature 'abcdPar,missing,missing'

genSeq(obj, r, seed)
generateRandomSequences 29

## S4 method for signature 'bbcdPar,numeric,numeric'

genSeq(obj, r, seed)

## S4 method for signature 'bbcdPar,numeric,missing'

genSeq(obj, r, seed)

## S4 method for signature 'bbcdPar,missing,numeric'

genSeq(obj, r, seed)

## S4 method for signature 'bbcdPar,missing,missing'

genSeq(obj, r, seed)

## S4 method for signature 'ebcPar,numeric,numeric'

genSeq(obj, r, seed)

## S4 method for signature 'ebcPar,missing,numeric'

genSeq(obj, r, seed)

## S4 method for signature 'ebcPar,numeric,missing'

genSeq(obj, r, seed)

## S4 method for signature 'ebcPar,missing,missing'

genSeq(obj, r, seed)

## S4 method for signature 'bsdPar,numeric,numeric'

genSeq(obj, r, seed)

## S4 method for signature 'bsdPar,numeric,missing'

genSeq(obj, r, seed)

## S4 method for signature 'bsdPar,missing,numeric'

genSeq(obj, r, seed)

## S4 method for signature 'bsdPar,missing,missing'

genSeq(obj, r, seed)

## S4 method for signature 'chenPar,numeric,numeric'

genSeq(obj, r, seed)

## S4 method for signature 'chenPar,numeric,missing'

genSeq(obj, r, seed)

## S4 method for signature 'chenPar,missing,numeric'

genSeq(obj, r, seed)

## S4 method for signature 'chenPar,missing,missing'

genSeq(obj, r, seed)
30 generateRandomSequences

## S4 method for signature 'crPar,numeric,numeric'

genSeq(obj, r, seed)

## S4 method for signature 'crPar,missing,numeric'

genSeq(obj, r, seed)

## S4 method for signature 'crPar,numeric,missing'

genSeq(obj, r, seed)

## S4 method for signature 'crPar,missing,missing'

genSeq(obj, r, seed)

## S4 method for signature 'gbcdPar,numeric,numeric'

genSeq(obj, r, seed)

## S4 method for signature 'gbcdPar,numeric,missing'

genSeq(obj, r, seed)

## S4 method for signature 'gbcdPar,missing,numeric'

genSeq(obj, r, seed)

## S4 method for signature 'gbcdPar,missing,missing'

genSeq(obj, r, seed)

## S4 method for signature 'hadaPar,numeric,numeric'

genSeq(obj, r, seed)

## S4 method for signature 'hadaPar,missing,numeric'

genSeq(obj, r, seed)

## S4 method for signature 'hadaPar,numeric,missing'

genSeq(obj, r, seed)

## S4 method for signature 'hadaPar,missing,missing'

genSeq(obj, r, seed)

## S4 method for signature 'mpPar,numeric,numeric'

genSeq(obj, r, seed)

## S4 method for signature 'mpPar,missing,numeric'

genSeq(obj, r, seed)

## S4 method for signature 'mpPar,numeric,missing'

genSeq(obj, r, seed)

## S4 method for signature 'mpPar,missing,missing'

genSeq(obj, r, seed)
generateRandomSequences 31

## S4 method for signature 'rpbrPar,missing,numeric'

genSeq(obj, r, seed)

## S4 method for signature 'rpbrPar,numeric,numeric'

genSeq(obj, r, seed)

## S4 method for signature 'rpbrPar,missing,missing'

genSeq(obj, r, seed)

## S4 method for signature 'rpbrPar,numeric,missing'

genSeq(obj, r, seed)

## S4 method for signature 'tbdPar,numeric,numeric'

genSeq(obj, r, seed)

## S4 method for signature 'tbdPar,missing,numeric'

genSeq(obj, r, seed)

## S4 method for signature 'tbdPar,numeric,missing'

genSeq(obj, r, seed)

## S4 method for signature 'tbdPar,missing,missing'

genSeq(obj, r, seed)

## S4 method for signature 'rtbdPar,numeric,numeric'

genSeq(obj, r, seed)

## S4 method for signature 'rtbdPar,missing,numeric'

genSeq(obj, r, seed)

## S4 method for signature 'rtbdPar,numeric,missing'

genSeq(obj, r, seed)

## S4 method for signature 'rtbdPar,missing,missing'

genSeq(obj, r, seed)

## S4 method for signature 'udPar,numeric,numeric'

genSeq(obj, r, seed)

## S4 method for signature 'udPar,missing,numeric'

genSeq(obj, r, seed)

## S4 method for signature 'udPar,numeric,missing'

genSeq(obj, r, seed)

## S4 method for signature 'udPar,missing,missing'

genSeq(obj, r, seed)
32 generateRandomSequences

Arguments
obj object specifying the randomization procedure, see randPar or createParam.
r numeric indicating the number of random sequences to be generated at random,
or missing.
seed a single value, interpreted as an integer, that specifies the seed for the random
number generation.

Details
genSeq generates randomization sequences for a randomization procedure as defined by the input
parameters. genSeq has two modes, according to the input.

1. genSeq(obj,r): gives r random sequences from the design specified by obj, along with the
parameters stored in obj.
2. genSeq(obj): gives one random sequences from the design specified by obj, along with the
parameters stored in obj.

The sequences are generated by using the Monte-Carlo sampling technique to sample from the
true distribution of the sequences according to the randomization procedure specified by obj. The
parameters of the randomization procedure are saved along with the sequences to ensure repro-
ducibility of the results.

Value
An object inheriting from randSeq, representing the r randomization sequences generated at ran-
dom for the specified randomization procedure. The output consists of the parameters used for
the generation of the randomization sequences (see createParam) and the matrix M that stores the
randomization sequences in its r rows. If r is missing, one sequence is generated by default.

Examples
# generate randomization sequences using Complete Randomization for N = 10
myPar <- crPar(10)
genSeq(myPar, 4)
genSeq(myPar)

# generate randomization sequences using the Random Allocation Rule for N = 10

myPar <- rarPar(10)
genSeq(myPar, 4)
genSeq(myPar)

# generate randomization sequences using the Maximal Procedure with mti = 2 and N = 10
myPar <- mpPar(10, 2)
genSeq(myPar, 4)
genSeq(myPar)
genNcps_new 33

genNcps_new Calculation of the NCPs of each randomization sequence for the dou-
bly noncentral t-distribution

Description
Computes the noncentrality parameters delta and lambda for the doubly noncentral t-distribution of
each randomization sequence.

Usage
genNcps_new(randSeq, bias, endp, weight = FALSE)

Arguments
randSeq a list of randSeq(rCrSeq or others) with possible varying N’s
bias a list of biases - corresponding to the different randSeq’s
endp object of the class endpoint.
weight if set to TRUE the weight will be set to 1, according to the paper

Value
a list containing the noncentrality parameters delta and lambda of all randomization sequences.

getCorGuesses Matrix of the guesses of the investigator

Description
Calculates the guesses of the investigator of a randomization list following the specified guessing
strategy.

Usage
getCorGuesses(randSeq, guessing)

Arguments
randSeq object of the class randSeq.
guessing object of the class corGuess.

Value
Matrix of the guesses of the investigator following the specified guessing strategy. No guess is
abbreviated with "nG".
34 getDesign

Examples
myPar <- bsdPar(10, 2)
M <- genSeq(myPar, 2)
type <- corGuess("CS")
getCorGuesses(M, type)

getDesFunc Type of Desirability function

Description

Generates a character vector which specifies the used desirability function and its parameters

Usage

getDesFunc(obj)

## S4 method for signature 'derringerLs'

getDesFunc(obj)

## S4 method for signature 'derringerRs'

getDesFunc(obj)

## S4 method for signature 'derringerTs'

getDesFunc(obj)

Arguments

obj object of the class desFunc.

Value

A character vector which specifies the used desirability function and its parameters

getDesign Design of a randomization procedure

Description

Generates a character vector which specifies the used randomization method

getDesign 35

Usage

getDesign(obj)

## S4 method for signature 'pbrPar'

getDesign(obj)

## S4 method for signature 'rarPar'

getDesign(obj)

## S4 method for signature 'rarSeq'

getDesign(obj)

## S4 method for signature 'abcdPar'

getDesign(obj)

## S4 method for signature 'abcdSeq'

getDesign(obj)

## S4 method for signature 'bbcdPar'

getDesign(obj)

## S4 method for signature 'bbcdSeq'

getDesign(obj)

## S4 method for signature 'ebcPar'

getDesign(obj)

## S4 method for signature 'bsdPar'

getDesign(obj)

## S4 method for signature 'bsdSeq'

getDesign(obj)

## S4 method for signature 'chenPar'

getDesign(obj)

## S4 method for signature 'chenSeq'

getDesign(obj)

## S4 method for signature 'crPar'

getDesign(obj)

## S4 method for signature 'crSeq'

getDesign(obj)

## S4 method for signature 'ebcSeq'

getDesign(obj)
36 getDesign

## S4 method for signature 'gbcdPar'

getDesign(obj)

## S4 method for signature 'gbcdSeq'

getDesign(obj)

## S4 method for signature 'hadaPar'

getDesign(obj)

## S4 method for signature 'hadaSeq'

getDesign(obj)

## S4 method for signature 'mpPar'

getDesign(obj)

## S4 method for signature 'mpSeq'

getDesign(obj)

## S4 method for signature 'pbrSeq'

getDesign(obj)

## S4 method for signature 'rRtbdSeq'

getDesign(obj)

## S4 method for signature 'rRpbrSeq'

getDesign(obj)

## S4 method for signature 'rpbrPar'

getDesign(obj)

## S4 method for signature 'tbdPar'

getDesign(obj)

## S4 method for signature 'rtbdPar'

getDesign(obj)

## S4 method for signature 'tbdSeq'

getDesign(obj)

## S4 method for signature 'udPar'

getDesign(obj)

## S4 method for signature 'udSeq'

getDesign(obj)

Arguments

obj object of the class randSeq or randPar.

getDesScores 37

Value
the name of the randomization procedure used

getDesScores Applying desirability functions on issues of individual randomization

sequences

Description
Applying desirability function on issues of individual randomization sequences.

Usage
getDesScores(assess, ..., weights)

## S4 method for signature 'assessment,missing'

getDesScores(assess, ..., weights)

## S4 method for signature 'assessment,numeric'

getDesScores(assess, ..., weights)

Arguments
assess object of class assessment.
... at least one object of class derFunc or a list of objects of the class derFunc.
weights weights for computing the geometric mean of several desirability scores. If
missing, the issues are automatically equally weighted.

Details
Randomization sequences behave differently with respect to issues like selection bias, chronological
bias, or loss in power estimation. The getDesScores function evaluates the behavior of random-
ization sequences with respect to these issues. The difference to the assess function is that it scales
them to \[0,1\] and makes them easier interpretable. The first argument should be a result of the
assess function. The second argument should be any number of derFunc objects that represent
the desirability functions. The last argument weights may be provided if the desirability functions
should be weighted differently.

Value
S4 object of class desirability summarizing the desirability of the randomization procedure.

See Also
Representation of randomization procedures: randPar
Generation of randomization sequences: genSeq
issues for the desirability of randomization sequences
Other desirability topics: derFunc, evaluate(), plotDes(), plotEv(), probUnDes()
38 getDistributionPars

Examples
# compute the desire-function for the full set of Random Allocation Rule for N = 4
sequences <- getAllSeq(rarPar(4))
issue1 <- corGuess("CS")
issue2 <- chronBias("linT", 0.25, "exact")
endp <- normEndp(mu = c(0,0), sigma = c(1,1))
A <- assess(sequences, issue1, issue2, endp = endp)
d1 <- derFunc(0.5, 0.75, 1)
d2 <- derFunc(0.05, 0.1, 1)

D1 <- getDesScores(A, d1, d2)

summary(D1)

D2 <- getDesScores(A, d1, d2, weights = c(3/4, 1/4))

summary(D2)

getDistributionPars Get distribution parameters of a randomization list

Description
Generates a matrix of the distribution parameters of the included patients in the clinical trial.

Usage
getDistributionPars(randSeq, issue, endp)

## S4 method for signature 'randSeq,missing,survEndp'

getDistributionPars(randSeq, endp)

## S4 method for signature 'randSeq,chronBias,survEndp'

getDistributionPars(randSeq, issue, endp)

## S4 method for signature 'randSeq,selBias,survEndp'

getDistributionPars(randSeq, issue, endp)

## S4 method for signature 'randSeq,combinedBias,survEndp'

getDistributionPars(randSeq, issue, endp)

## S4 method for signature 'randSeq,combinedBiasStepTrend,survEndp'

getDistributionPars(randSeq, issue, endp)

Arguments
randSeq object of the class randSeq.
issue object of the class issue (optional).
endp object of the class endpoint.
getExpectation 39

Value
a matrix of the distribution parameters of the included patients in the clinical trial.

Examples
# return the shape and scale parameters of a Weibull distribution
endp <- survEndp(shape = c(1,1), scale = c(0.5,1), cenTime = 10, cenRate = 0.01)
biasSB <- selBias("CS", log(2), "exact")
randSeq <- genSeq(rpbrPar(rb = 2, N = 12))
getDistributionPars(randSeq,biasSB,endp)

getExpectation Get expectations of a randomization list

Description
Generates a matrix of the expectations of the included patients in the clinical trial.

Usage
getExpectation(randSeq, issue, endp)

## S4 method for signature 'randSeq,missing,survEndp'

getExpectation(randSeq, endp)

## S4 method for signature 'randSeq,missing,expEndp'

getExpectation(randSeq, endp)

## S4 method for signature 'randSeq,missing,normEndp'

getExpectation(randSeq, endp)

## S4 method for signature 'randSeq,power,normEndp'

getExpectation(randSeq, issue, endp)

## S4 method for signature 'randSeq,chronBias,normEndp'

getExpectation(randSeq, issue, endp)

## S4 method for signature 'randSeq,chronBias,expEndp'

getExpectation(randSeq, issue, endp)

## S4 method for signature 'randSeq,chronBias,survEndp'

getExpectation(randSeq, issue, endp)

## S4 method for signature 'randSeq,chronBias,missing'

getExpectation(randSeq, issue)

## S4 method for signature 'randSeq,selBias,normEndp'

40 getExpectation

getExpectation(randSeq, issue, endp)

## S4 method for signature 'randSeq,selBias,expEndp'

getExpectation(randSeq, issue, endp)

## S4 method for signature 'randSeq,selBias,survEndp'

getExpectation(randSeq, issue, endp)

## S4 method for signature 'randSeq,selBias,missing'

getExpectation(randSeq, issue)

## S4 method for signature 'randSeq,combinedBias,normEndp'

getExpectation(randSeq, issue, endp)

## S4 method for signature 'randSeq,combinedBias,expEndp'

getExpectation(randSeq, issue, endp)

## S4 method for signature 'randSeq,combinedBias,survEndp'

getExpectation(randSeq, issue, endp)

## S4 method for signature 'randSeq,combinedBiasStepTrend,normEndp'

getExpectation(randSeq, issue, endp)

## S4 method for signature 'randSeq,combinedBiasStepTrend,expEndp'

getExpectation(randSeq, issue, endp)

## S4 method for signature 'randSeq,combinedBiasStepTrend,survEndp'

getExpectation(randSeq, issue, endp)

Arguments
randSeq object of the class randSeq.
issue object of the class issue (optional).
endp object of the class endpoint (optional).

Details
It is assumed that the expectations of the included patients in a clinical trial can be influenced in
three different ways:

• The strength of selection bias and the guessing strategy of the investigator (see selBias).
• The strength of a linear time trend, which is described by an object of the class chronBias.
• The expectations of the investigated treatment groups can be different (see e.g. normEndp).

Value
A matrix of the expectations of the included patients in the clinical trial.
getProbabilities 41

Examples
# get Expectation for a normal endpoint
myPar <- bsdPar(10, 2)
M <- genSeq(myPar, 2)
cs <- selBias("CS", 2, "sim")
endp <- normEndp(mu = c(2, 2), sigma = c(1, 1))
getExpectation(M, cs, endp)

# get Expectation for an exponential endpoint

cs <- selBias("CS", 0.1 , "sim")
endp <- expEndp(lambda = c(0.5, 1), cenTime = 10, cenRate = 0.01)
getExpectation(M, cs, endp)

getProbabilities Theoretical probability for randomization sequences

Description
Calculate theoretical probability for observed randomization sequences

Usage
getProb(obj)

## S4 method for signature 'rarSeq'

getProb(obj)

## S4 method for signature 'abcdSeq'

getProb(obj)

## S4 method for signature 'bbcdSeq'

getProb(obj)

## S4 method for signature 'bsdSeq'

getProb(obj)

## S4 method for signature 'chenSeq'

getProb(obj)

## S4 method for signature 'crSeq'

getProb(obj)

## S4 method for signature 'ebcSeq'

getProb(obj)

## S4 method for signature 'gbcdSeq'

42 getRandomizationList

getProb(obj)

## S4 method for signature 'hadaSeq'

getProb(obj)

## S4 method for signature 'mpSeq'

getProb(obj)

## S4 method for signature 'pbrSeq'

getProb(obj)

## S4 method for signature 'tbdSeq'

getProb(obj)

## S4 method for signature 'udSeq'

getProb(obj)

Arguments
obj object of a class inheriting from randSeq. Formal representation of a random-
ization sequences together with the parameters that belong to the procedure that
generated the sequences.

Value
a matrix with theoretical probabilities for observed randomization sequences

Examples
myPar <- bsdPar(10, 2)
M <- genSeq(myPar, 2)
getProb(M)

# all Sequences
par <- pbrPar(bc=c(2,2))
refSet <- getAllSeq(myPar)
probs <- getProb(refSet)

# sequences with probabilities

cbind(probs, refSet$M)

getRandomizationList Accessor function for the randomization list

Description
Get the randomization list coded in its groups.
get_p_values_new 43

Usage
getRandList(obj)

Arguments
obj object specifying the randomization procedure, see randPar or createParam.

Value
A matrix with all randomization sequences of a S4 object

Examples
myPar <- bsdPar(10, 2)
M <- genSeq(myPar, 2)
getRandList(M)

get_p_values_new Calculating p values

Description
Computes the p values based on the noncentrality parameters delta and lambda for the doubly
noncentral t-distribution

Usage
get_p_values_new(delta, lambda, N, alpha = 0.05, df = sum(N - 2))

Arguments
delta The first noncentrality parameter
lambda The second noncentrality parameter
N the amount of patients in the trial
alpha significance level
df degrees of freedom

Value
a p value
44 GSD_allocation

GSD_allocation Calculates the Type I error for different randomization sequences from
a randomization procedure for a group sequential design

Description
Calculates the Type I error for different randomization sequences from a randomization procedure
for a group sequential design

Usage
GSD_allocation(
n,
reps,
sfu,
K,
rp,
seed = 42,
ui = "No",
rb = 4,
mti = 3,
p = 2/3
)

Arguments
n total sample size
reps number of simulations to be conducted
sfu Group sequential design used (currently available: "Pocock" - Pocock, "OF"
- O’Brien & Fleming, sfLDPocock - Lan & DeMets with Pocock like alpha
spending function, sfLDOF - Lan & DeMets with O’Brien & Fleming like alpha
spending function)
K number of stages
rp the randomization procedure used (currently available: '"CR"', '"RAR"', '"BSD"',
'"CHEN"', '"PBR"', '"MP"')
seed Randomization seed
ui for Lan & DeMets design. Update critical values after each stage according to
allocation ratio observed if set to "yes".
rb Block size for randomization procedure PBR.
mti Maximum tolerated imbalance for randomization procedure BSD and MP.
p Probability p in favor of the treatment with fewer allocations for EBC and
CHEN.
GSD_allocation_seq 45

Value

A list consisting of a vector of Type I errors for each randomization sequence generated from the
randomization procedure and a S4 object of the class of the randomization procedure.

Examples
#Simulate a group sequential design according to O'Brien and Fleming's design with 24 patients,
#10 simulation runs,3 Stages using Random Allocation Rule as a randomization procedure.
GSD_allocation(n=24, reps=10, sfu="OF", K=3, rp="RAR")
#Simulate a group sequential design according to Lan and deMets design with a Pocock
#like alpha spending function with 18 patients, 10 simulation runs,
#3 Stages using Permuted Block Randomization with block size 4
#as a randomization procedure without updating the critical values after each stage.
library(gsDesign)
GSD_allocation(n=18, reps=10, sfu=sfLDPocock, K=3, rp="PBR", ui="no", rb=4)

GSD_allocation_seq Calculates the Type I error for a randomization sequence in a group

sequential design

Description

Calculates the Type I error for a randomization sequence in a group sequential design

Usage

GSD_allocation_seq(sfu, K, seq, ui = "No")

Arguments

sfu Group sequential design used (currently available: "Pocock" - Pocock, "OF"
- O’Brien & Fleming, sfLDPocock - Lan & DeMets with Pocock like alpha
spending function, sfLDOF - Lan & DeMets with O’Brien & Fleming like alpha
spending function)
K number of stages
seq List of consecutive treatment allocations. 1 for first treatment A, 2 for second
treatment.
ui Only for Lan & DeMets design. Update critical values after each stage according
to allocation ratio observed if set to "yes".

Value

A list of type I error probabilities for each stage.

46 hadaPar

Examples
#Simulate a group sequential design according to Pocock's design with 24 patients
#and the following consecutive treatment allocation:
#A, A, B, A, A, B, A, B, A, B, A, B, A, B, A, B, B, B, A, B, B, A, B, B
GSD_allocation_seq(sfu ="Pocock", K=3, seq = c(1,1,0,1,1,0,1,1,1,0,1,0,1,0,1,0,0,0,1,0,0,1,0,0))
#Simulate a group sequential design according to Lan and DeMets with O'Brien & Fleming
#like alpha spending with 24 patients and the following consecutive treatment allocation:
#A, A, B, A, A, B, A, B, A, B, A, B, A, B, A, B, B, B, A, B, B, A, B, B
library(gsDesign)
GSD_allocation_seq(sfu =sfLDOF, K=3, seq = c(1,1,0,1,1,0,1,1,1,0,1,0,1,0,1,0,0,0,1,0,0,1,0,0))

hadaPar Representing Hadamard Randomization

Description
Represents the randomization procedure Hadamard Randomization.

Usage
hadaPar(N, groups = LETTERS[1:2])

Arguments
N integer for the total sample size of the trial.
groups character vector of labels for the different treatments.

Details
Hadamard randomization has been proposed by R.A. Bailey. The key idea is to use the columns
of a special Hadamard Matrix as a randomization scheme. The implemented algorithm uses the
Hadamard Matrix with N=12 columns proposed in the paper, see references.

Value
S4 object of the class hadaPar.

Note
getProb and getAllSeq are currently only supported for hadaPar with total sample size N=12.

References
R.A. Bailey and P.R. Nelson (2003) Hadamard Randomization: A valid restriction of random per-
muted blocks. Biometrical Journal, 45, 554-60.
imbal 47

See Also
Other randomization procedures: abcdPar, bbcdPar, bsdPar, chenPar, crPar, createParam(),
ebcPar, gbcdPar, mpPar, pbrPar, rarPar, rpbrPar, rtbdPar, tbdPar, udPar

imbal Representing the allocation imbalance

Description
Represents the imbalance of the treatment assignments of patients in a clinical trial.

Usage
imbal(type)

Arguments
type character string, should be one of "imb", "absImb", "loss", or "maxImb", see
Details.

Details
Balance of the treatment assignment of patients can be an issue in the design of a clinical trial. The
imbal function is a constructor function for an S4 object of class imbal representing the issue of
imbalance of a clinical trial. The parameter type can take the following values: The type

"imb" the final imbalance, i.e. difference in group sizes at the end of a trial
"absImb" the absolute value of the final imbalance
"loss" the loss in power estimation, i.e. imb^2/N
"maxImb" the maximal attained imbalance during the trial

Value
S4 object of class imbal, a formal representation of the issue of imbalance in a clinical trial.

References
A.C. Atkinson (2014) Selecting a biased coin design. Statistical Science, 29, Vol. 1, 144-163.

See Also
Other issues: chronBias, combineBias(), corGuess, issue, selBias, setPower()
48 issue

issue Assessment criteria for clinical trials

Description

Summarizes the criteria for the assessment of randomization procedures.

Details

Randomization in clinical trials is supposed to control certain properties in clinical trials. In the
randomizeR package, these properties are called issues. It is crucial to decide which of the issues
is relevant in the present clinical trial, because a randomization procedure that manages well one
issue might behave very badly for another. The issues include

• Selection bias can occur if future treatment allocations are predictable due to restricted ran-
domization and unmasking of past treatment assignments. The influence of selection bias on
the test decision is represented by the selBias class. The measure for the predictability of
a randomization procedure is implemented in the corGuess class representing the expected
number of correct guesses.
• Chronological bias can occur if a time trend is present in the data. Time trends occur due
to learning curves, relaxed inclusion/ exclusion criteria or new co-medication. Chronological
bias is represented by the chronBias class.
• Additive combination of chronological and selection bias may occur if a time trend and
selection bias are present in the data. The combined bias is represented by the combineBias
class.
• Balance is important in order to ensure proper power estimation properties of the treatments.
However, a high degree of balance favors selection bias. Depending on the clinical context, a
randomization procedure should be chosen that admits a suitable imbalance. Imbalance bias
is represented by the imbal class. The power loss due to imbalance can be assessed directly
via the setPower class

See Also

Representation of randomization procedures: randPar

Generation of randomization sequences: genSeq
Assessment of randomization sequences: assess
Comparison of randomization sequences: compare
Other issues: chronBias, combineBias(), corGuess, imbal, selBias, setPower()
K 49

K Function returning the number of trial arms slot of an S4 object

Description

Function returning the number of trial arms slot of an S4 object

Usage

K(obj)

Arguments

obj object of class randPar

Value

The number of trial arms

lambda Method returning the rate parameter of an expEndp S4 object

Description

Method returning the rate parameter of an expEndp S4 object

Usage

lambda(obj)

Arguments

obj object of class expEndp

50 mpPar

method Function returning the method of an S4 object

Description
Function returning the method of an S4 object

Usage
method(obj)

Arguments
obj object inheriting from randPar

Value
The method of an S4 object

mpPar Representing Maximal Procedure

Description
Represents the Maximal Procedure.

Usage
mpPar(N, mti, ratio = c(1, 1), groups = LETTERS[1:2])

Arguments
N integer for the total sample size of the trial.
mti maximum tolerated imbalance in patient numbers during the trial.
ratio vector of length K. The total sample number N and all used block lengths (bc)
have to be divisible by sum(ratio).
groups character vector of labels for the different treatments.

Details
Fix the total sample size N and the mti. Afterwards, the patients are assigned to each treatment arm
according to the ratio. All randomization sequences are equiprobable.

Value
S4 object of the class mpPar.
mti 51

References

V.W. Berger, A. Ivanova and M.D. Knoll (2003) Minimizing predictability while retaining balance
through the use of less restrictive randomization procedures. Statistics in Medicine, 19, 3017-28.

See Also

Other randomization procedures: abcdPar, bbcdPar, bsdPar, chenPar, crPar, createParam(),

ebcPar, gbcdPar, hadaPar, pbrPar, rarPar, rpbrPar, rtbdPar, tbdPar, udPar

mti Function returning the MTI slot of an S4 object

Description

Function returning the MTI slot of an S4 object

Usage

mti(obj)

Arguments

obj object of class bsdPar or mpPar

mu Access the expectation value slot of a normEndp S4 object

Description

Access the expectation value slot of a normEndp S4 object

Usage

mu(obj)

Arguments

obj object of class normEndp

52 normEndp

N Function returning the sample size slot of an S4 object

Description
Function returning the sample size slot of an S4 object

Usage
N(obj)

Arguments
obj object inheriting from randPar

Value
the sample size slot of an S4 object

normEndp Representation of normally distributed endpoints

Description
Represents normally distributed endpoints in clinical trials.

Usage
normEndp(mu, sigma)

Arguments
mu vector of the expected responses of the treatment groups, should have length K
(i.e. one entry for each treatment group).
sigma vector of the standard deviations in each treatment group, should have length K
(i.e. one entry for each treatment group).

Details
The normEnd function is a constructor function for an S4 object of the class normEnd representing
a normally distributed endpoint in a clinical trial. In conjunction with the assess function, normal
endpoints admit the calculation of the exact type-I-error probability and power.

Value
A S4 object that represents a normally distributed endpoint in a clinical trial
overview 53

See Also
Compute exact or simulated type-I-error: assess.
Other endpoint types: expEndp, survEndp

Examples
# set the parameters of two normally distributed endpoints
endp <- normEndp(mu = c(1, 2), sigma = c(1, 1))

overview Overview over the parameters used in the randomizeR package

Description
This list of parameters yields a comprehensive overview of the parameters used in the randomizeR
package.

Arguments
a nonnegative parameter which controls the degree of randomness: For decreasing
a the allocations become deterministic, while for increasing a the randomization
procedure tends to complete randomization.
accrualTime duration of the accrual period in a survival study.
add integer representing the number of balls that are added to the urn in each step.
alpha the significance level of the test in each simulation.
bc vector which contains the lengths k_1,...,k_l of each block. This means that
the vector bc will have one entry for each block.
b numeric vector of length at most 2 specifying the weight(s) for the punishment
of deviations from the target value.
cenRate exponential censoring rate in a survival study.
cenTime total duration of a survival study (maximum length of followup).
d effect size.
df degrees of freedom (i.a. N-2).
eta numeric specifying the magnitude of selection bias.
file A connection, or a character string naming the file to write to.
filledBlock logical whether the last block should be filled or not.
FTI final tolerated imbalance. This is the difference in number of patients of groups
A and B that is permitted at the end of a trial. Usually this is set to zero.
groups character vector of labels for the different treatments.
ini integer representing the initial urn composition.
54 overview

k length of the block to be permuted. k should be divisible by the number of

treatment arms.
K number of treatment groups (e.g. K=2 if we compare one experimental against
one control treatment).
lb lower bound for the starting value of the poisson distribution.
lambda vector of the exponential rate parameters in each treatment group.
method method that is used to generate the (random) allocation sequence. It can take
values PBR, RAR, HAD, PWR, EBC, BSD, CR, TBD, UD, and MP.
mti maximum tolerated imbalance in patient numbers during the trial.
mu vector of the expected responses of the treatment groups, should have length K
(i.e. one entry for each treatment group).
N integer for the total sample size of the trial.
name name of a variable.
obj object specifying the randomization procedure, see randPar or createParam.
object any R object.
p success probability of the biased coin (e.g. in Efron’s Biased Coin Design).
pr vector with patient responses, i.e. each patients resulting value after the treat-
ment.
q "cut-off" value in [0.5,1]. This is the ratio of patients up from which the
experimenter imposes selection bias on the data.
r numeric indicating the number of random sequences to be generated at random,
or missing.
ratio vector of length K. The total sample number N and all used block lengths (bc)
have to be divisible by sum(ratio).
rb block lengths of the blocks that can be selected equiprobable at random.
rho nonnegative parameter which my be adjusted according to how strongly it is
desired to balance the experiment. If rho = 1, we have Wei’s urn design with
alpha = 0. If rho = 0, we have complete randomization.
rsob randomization sequence (of one block).
rs randomization sequence (of all blocks).
S matrix for the computation of the probabilities in the maximal procedure.
saltus integer or missing specifying the patient index (i.e. position) of the step in case
of step time trend.
seed a single value, interpreted as an integer, that specifies the seed for the random
number generation.
sigma vector of the standard deviations in each treatment group, should have length K
(i.e. one entry for each treatment group).
SLs numeric vector of length at most 2 specifying the lower and/or upper specified
border.
theta factor of the time trend for further details see type.
pbrPar 55

type character vector indicating which biasing strategy the experimenter is using (se-
lection bias) and which other bias is present in the clinical trial (e.g. time trend).
All biases included in the vector are combined (i.e. added up) to form the total
bias. Possible values are "none" (if no bias occurs), "CS" (resp. "DS") (if the ex-
perimenter uses the convergence (resp. divergence) strategy to invoke selection
bias), LinT for linear time trend, LogT for log-linear time trend, StepT for step
time trend, SigT for sigmoid time trend, PWR for knowledge of all up to the first
observation in each block, MTI the next observation after reaching the maximal
tolerated imbalance is reached will be known to the physician.
TV numeric specifying the optimal desired value called the target value.
ub upper bound for the last value of the poisson distribution.
varEq logical parameter for the [Link]: Shall the variances be treated as equal (TRUE=
[Link]) or different (FALSE= [Link]).
x a variable x.
allocRatio numerical vector that represents the allocation ratio for the different strata in a
clinical trial
strata numeric specifying the number of strata in a clinical trial
maxcombo logical specifying if the maxcombo test is used
weights numeric specifying the weights used for the test. Unless specified an unweighted
test is conducted.

pbrPar Representing Permuted Block Randomization

Description
Represents the randomization procedure Permuted Block Randomization.

Usage
pbrPar(bc, K = 2, ratio = rep(1, K), groups = LETTERS[1:K])

Arguments
bc vector which contains the lengths k_1,...,k_l of each block. This means that
the vector bc will have one entry for each block.
K number of treatment groups (e.g. K=2 if we compare one experimental against
one control treatment).
ratio vector of length K. The total sample number N and all used block lengths (bc)
have to be divisible by sum(ratio).
groups character vector of labels for the different treatments.
56 plot

Details
Fix the block constellation bc, the number of treatment groups K, and the vector of the ratio.
Afterwards, in each block the patients are assigned according to the ratio to the corresponding
treatment groups. All generated randomization sequences are equiprobable.

Value
S4 object of the class pbrPar.

References
W. F. Rosenberger and J. M. Lachin (2002) Randomization in Clinical Trials. Wiley.

See Also
Other randomization procedures: abcdPar, bbcdPar, bsdPar, chenPar, crPar, createParam(),
ebcPar, gbcdPar, hadaPar, mpPar, rarPar, rpbrPar, rtbdPar, tbdPar, udPar

plot Generic plotting of comparison objects

Description
Generic plotting of comparison objects

Usage
plot(x, y, ...)

## S4 method for signature 'comparison,character'

plot(x, y)

## S4 method for signature 'comparison,missing'

plot(x, y)

Arguments
x object of class comparison.
y character "boxplot", or "violin", or "missing".
... "missing"

Details
Creates a box- or violinplot of an object x of the class comparison.

Value
A plot created with the additional package ggplot2.
plotDes 57

See Also

compare for creating S4 objects of the class comparison

Examples

# compare Random Allocation Rule and Big Stick for N = 4 with respect to
# correct guesses
RAR <- getAllSeq(rarPar(4))
BSD <- getAllSeq(bsdPar(4, mti = 2))
corGuess <- corGuess("CS")
comp <- compare(corGuess, RAR, BSD)
plot(comp)

plotDes desScore plotting

Description

Plot of an desScore object.

Usage

plotDes(desScore, labels, colAv = "red", quantiles = FALSE)

Arguments

desScore object of type desScore.

labels labels used in the plot. Can be NULL.
colAv color of the line representing the average of the desirability scores in the plot.
quantiles logical whether the quantiles should be depicted in the plot.

Value

a plot of an desScore object

See Also

Other desirability topics: derFunc, evaluate(), getDesScores(), plotEv(), probUnDes()

58 plotEv

Examples
# compute the desirability scores of the full set of PBR(4)
sequences <- getAllSeq(rarPar(4))
issue1 <- corGuess("CS")
issue2 <- chronBias("linT", 1/4, "exact")
endp <- normEndp(mu = c(0,0), sigma = c(1,1))
A <- assess(sequences, issue1, issue2, endp = endp)
d1 <- derFunc(0.5, 0.75, 1)
d2 <- derFunc(0.05, 0.1, 1)

D <- getDesScores(A, d1, d2)

summary(D)
plotDes(D)
plotDes(D, quantiles = TRUE)

plotEv Evaluation plotting

Description
Plot of an evaluation object.

Usage
plotEv(evaluation, labels, cols)

Arguments
evaluation object of type evaluation.
labels labels used in the plot. Can be NULL.
cols colors of the lines representing the desirability scores in the plot. Can be NULL.

Value
A plot of an evaluation object

See Also
Other desirability topics: derFunc, evaluate(), getDesScores(), plotDes(), probUnDes()

Examples
# compare Random Allocation Rule to Big Stick Design with respect to different issues
# and their corresponding desirability functions
issue1 <- corGuess("CS")
issue2 <- chronBias(type = "linT", theta = 1/4, method = "exact")
RAR <- getAllSeq(rarPar(4))
BSD <- getAllSeq(bsdPar(4, mti = 2))
plotSeq 59

A1 <- assess(RAR, issue1, issue2, endp = normEndp(c(0,0), c(1,1)))

A2 <- assess(BSD, issue1, issue2, endp = normEndp(c(0,0), c(1,1)))

d1 <- derFunc(TV = 0.5, 0.75, 2)

d2 <- derFunc(0.05, c(0, 0.1), c(1, 1))
DesScore <- getDesScores(A1, d1, d2, weights = c(5/6, 1/6))
DesScore2 <- getDesScores(A2, d1, d2, weights = c(5/6, 1/6))

E <- evaluate(DesScore, DesScore2)

plotEv(E)

plotSeq Sequence plotting

Description
Plot all randomization sequences of a randSeq object

Usage
plotSeq(sequences, plotAllSeq = FALSE, emph = NA, rs = NA)

Arguments
sequences object of type randSeq
plotAllSeq logical. If plotAllSeq=TRUE, the complete set of randomization sequences will
be plotted in light gray.
emph integer indicating which sequence should be highlighted in blue.
rs vector of a randomization sequence that should be highlighted.

Value
A plot of all randomization sequences of a randSeq object.

probUnDes Computing the probability of having desirability scores of zero

Description
Computing the probability of having desirability scores of zero for each desirability function applied
to an issue.
60 probUnDes

Usage

probUnDes(desScore)

## S4 method for signature 'desScores'

probUnDes(desScore)

Arguments

desScore an object of the class desScores, i.e. an object resulting from applying the
function getDesScores

Details

The function probUnDes expects an object that results from the getDesScores function. For each
issue it computes the probability that it achieves an undesirable score, i.e. a desirability score of 0.
In doing so, it weights the zero desirability scores with the probability that the sequence occurs.

Value

S4 object of class probUnDesirable computing the probability of getting undesirable scores, i.e.
desirability scores of 0.

See Also

Representation of randomization procedures: randPar

Generation of randomization sequences: genSeq
issues for the desirability of randomization sequences
Other desirability topics: derFunc, evaluate(), getDesScores(), plotDes(), plotEv()

Examples
# compare Random Allocation Rule to Big Stick Design with respect to different issues
# and their corresponding desirability functions
RAR <- getAllSeq(rarPar(4))
issue1 <- corGuess("CS")
issue2 <- corGuess("DS")
A1 <- assess(RAR, issue1, issue2)

d1 <- derFunc(TV = 0.1, 0.7, 2)

d2 <- derFunc(0.5, c(0.3, 0.8), c(1, 1))
DesScore <- getDesScores(A1, d1, d2, weights = c(5/6, 1/6))

probUnDes(DesScore)
randBlocks 61

randBlocks Function returning the block slot of an S4 object

Description
Function returning the block slot of an S4 object

Usage
randBlocks(obj)

Arguments
obj object of class pbrPar

Value
a vector with the lengths of each random block of a pbrPar object

randPar Settings for randomization procedures

Description
Randomization procedures in randomizeR are represented by objects that inherit from randPar.
The representation can then be used in order to generate randomization sequences. In order generate
a representation of a randomization procedure, call createParam or one of the following functions.

Supported randomization procedures

• Complete Randomization (crPar)
• Random Allocation Rule (rarPar)
• Permuted Block Randomization (pbrPar)
• Permuted Block Randomization with random block length (rpbrPar)
• Truncated Binomial Design (tbdPar)
• Truncated Binomial Design with random block length (rtbdPar)
• Efron’s Biased Coin Design (ebcPar)
• Big Stick Design (bsdPar)
• Maximal Procedure (mpPar)
• Wei’s Urn Design (udPar)
• Chen’s Design (chenPar)
• Generalized Biased Coin Design (gbcdPar)
• Accelerated Biased Coin Design (abcdPar)
• Bayesian Biased Coin Design (bbcdPar)
• Hadamard Randomization (hadaPar)
62 rarPar

See Also
Generate randomization sequences genSeq. Calculate the the complete set of randomization se-
quences of a randomization procedure. getAllSeq.

randSeq-class An S4 Class for the representation of randomization sequences

Description
This set of classes provides functionality of storing randomization sequences of different random-
ization procedures along with the parameters representing the design.

Slots
N total number of patients included in the trial
M matrix containing randomization sequences of length N in its rows.
K number of treatment groups
groups character string of length K defining the names of the treatment groups
ratio ratio of patients between the different groups

rarPar Representing Random Allocation Rule

Description
Represents the randomization procedure Random Allocation Rule.

Usage
rarPar(N, K = 2, ratio = rep(1, K), groups = LETTERS[1:K])

Arguments
N integer for the total sample size of the trial.
K number of treatment groups (e.g. K=2 if we compare one experimental against
one control treatment).
ratio vector of length K. The total sample number N and all used block lengths (bc)
have to be divisible by sum(ratio).
groups character vector of labels for the different treatments.
ratio 63

Details

Fix a total sample size N the number of treatment groups K, and the vector of the ratio. After-
wards, all patients are assigned according to the ratio to the corresponding treatment groups. All
randomization sequences are equiprobable.

Value

S4 object of the class rarPar.

References

W. F. Rosenberger and J. M. Lachin (2002) Randomization in Clinical Trials. Wiley.

See Also

Other randomization procedures: abcdPar, bbcdPar, bsdPar, chenPar, crPar, createParam(),

ebcPar, gbcdPar, hadaPar, mpPar, pbrPar, rpbrPar, rtbdPar, tbdPar, udPar

ratio Function returning the allocation ratio slot of an S4 object

Description

Function returning the allocation ratio slot of an S4 object

Usage

ratio(obj)

Arguments

obj object of class randPar

Value

A vector containng the allocation ratio of an S4 object

64 rpbrPar

rho Function returning the adjusting parameter rho slot of an S4 object

Description
Function returning the adjusting parameter rho slot of an S4 object

Usage
rho(obj)

Arguments
obj object of class randPar

Value
the value of the rho parameter of an S4 object

rpbrPar Representing Randomized Permuted Block Randomization

Description
Represents the randomization procedure Randomized Permuted Block Randomization.

Usage
rpbrPar(
N,
rb,
K = 2,
ratio = rep(1, K),
groups = LETTERS[1:K],
filledBlock = FALSE
)

Arguments
N integer for the total sample size of the trial.
rb block lengths of the blocks that can be selected equiprobable at random.
K number of treatment groups (e.g. K=2 if we compare one experimental against
one control treatment).
ratio vector of length K. The total sample number N and all used block lengths (bc)
have to be divisible by sum(ratio).
groups character vector of labels for the different treatments.
filledBlock logical whether the last block should be filled or not.
rtbdPar 65

Details
Fix the possible random block lengths rb, the number of treatment groups K, the sample size N and
the vector of the ratio. Afterwards, one block length is randomly selected of the random block
lengths. The patients are assigned according to the ratio to the corresponding treatment groups. This
procedure is repeated until N patients are assigned. Within each block all possible randomization
sequences are equiprobable.

Value
S4 object of the class rpbrPar.

References
W. F. Rosenberger and J. M. Lachin (2002) Randomization in Clinical Trials. Wiley.

See Also
Other randomization procedures: abcdPar, bbcdPar, bsdPar, chenPar, crPar, createParam(),
ebcPar, gbcdPar, hadaPar, mpPar, pbrPar, rarPar, rtbdPar, tbdPar, udPar

rtbdPar Representing Randomized Truncated Binomial Design

Description
Represents the randomization procedure Randomized Truncated Binomial Design.

Usage
rtbdPar(N, rb = N, groups = LETTERS[1:2], filledBlock = FALSE)

Arguments
N integer for the total sample size of the trial.
rb block lengths of the blocks that can be selected equiprobable at random.
groups character vector of labels for the different treatments.
filledBlock logical whether the last block should be filled or not.

Details
Fix the possible random block lengths rb and the sample size of the trial N. Afterwards, one block
length is randomly selected of the random block lengths. In this block a fair coin is tossed for
the patient assignments until half of the patients have been assigned to one of the treatment arms.
Afterwards, the block is filled with the other treatment. This procedure is repeated until N patients
are assigned.
66 saveAssess

Value

S4 object of the class rtbdPar.

References

W. F. Rosenberger and J. M. Lachin (2002) Randomization in Clinical Trials. Wiley.

See Also

Other randomization procedures: abcdPar, bbcdPar, bsdPar, chenPar, crPar, createParam(),

ebcPar, gbcdPar, hadaPar, mpPar, pbrPar, rarPar, rpbrPar, tbdPar, udPar

saveAssess Saving an assess object

Description

Saves the full information of an assess object in a .csv data sheet.

Usage

saveAssess(obj, file = "[Link]")

Arguments

obj object of class assessment, e.g. the output of the assess function.
file A connection, or a character string naming the file to write to.

Value

Creates a .csv data in the home folder.

See Also

Other saving functions: saveRand()

saveRand 67

saveRand Saving a randomization lists

Description

Saves the parameters of a randSeq object in a .csv data sheet.

Usage

saveRand(obj, file = "[Link]")

Arguments

obj object of class randSeq containing a single randomization sequence.

file A connection, or a character string naming the file to write to.

Value

Creates a .csv data in the home folder and saves the randomization list as a column vector.

See Also

Other saving functions: saveAssess()

scale Method returning the scale parameter of an survEndp S4 object

Description

Method returning the scale parameter of an survEndp S4 object

Usage

scale(obj)

Arguments

obj object of class survEndp

68 selBias

seed Function returning the allocation seed slot of an object

Description
Returns the seed that was either generated at random or user specified. The seed can be specified
for any random operation e.g. genSeq.

Usage
seed(obj)

Arguments
obj object specifying the randomization procedure, see randPar or createParam.

selBias Representing selection bias

Description
Represents the issue of selection bias in a clinical trial.

Usage
selBias(type, eta, method, alpha = 0.05, delta = 0)

Arguments
type character string, should be one of "CS", "CS2" or "DS", see Details.
eta numeric specifying the magnitude of selection bias.
method character string, should be one of "sim" or "exact", see Details.
alpha significance level.
delta parameter of selection bias used for calculating shape and scale of the Weibull
distribution with exponential endpoints

Details
Selection bias can be an issue in the design of a clinical trial. The selBias function is a constructor
function for an S4 object of the class selBias representing the issue of third order selection bias
in a clinical trial. It supports two possible modes, method="sim" and method="exact". This
representation is particularly useful in interaction with the assess function.
selBias 69

method="sim" Represents the simulated type-I-error rate given the level alpha, the selection ef-
fect eta and the biasing strategy type. When calling assess for a selBias object with
method="sim", one test decision is computed for each sequence of randSeq. The type-I-error
rate (power) is the proportion of falsely (correctly) rejected null hypotheses.
method="exact" Represents the exact type-I-error probability given the level alpha, the selection
effect eta and the biasing strategy type. When calling assess for a selBias object with
method="exact", the p-value of each randomization sequence is computed. For normal end-
points and two treatment groups these p-values are exact values which can be calculated from
the sum of the corresponding quantiles of the doubly noncentral t-distribution. For more than
two treatment groups, exact p-values are computed using a doubly noncentral F distribution.
For exponential endpoints the p-values are obtained using an approximation formula.

It also supports three types of selection bias:

type="DS" Refers to the divergence strategy according to Blackwell and Hodges (1957). Under
this guessing strategy, the investigator guesses that the upcoming treatment is the one that has
so far been allocated *more* frequently.
type="CS" Refers to the convergence strategy according to Blackwell and Hodges (1957). Under
this guessing strategy, the investigator guesses that the upcoming treatment is the one that
has so far been allocated *less* frequently. In multi-arm trials, type="CS" refers to the first
generalization of the convergence strategy according to Uschner et al (2018). The investigator
guesses the treatment that had been allocated less frequently whenever all the treatments of
the opposite group are larger than the smallest of the present group.
type="CS2" In trials with two treatment arms, type="CS2" is equivalent to type="CS". In multi-
arm trials, type="CS2" refers to the second generalization of convergence strategy according
to Uschner et al (2018). The investigator guesses the treatment that had been allocated less
frequently whenever all the treatments of the opposite group are larger than the smallest of the
present group.

Value
S4 object of class selBias, a formal representation of the issue of selection bias in a clinical trial.

References
D. Blackwell and J.L. Hodges Jr. (1957) Design for the control of selection bias. Annals of Mathe-
matical Statistics, 25, 449-60.
M. Proschan (1994) Influence of selection bias on the type-I-error rate under random permuted
block designs. Statistica Sinica, 4, 219-31.
D. Uschner, R.-D. Hilgers, N. Heussen (2018) The impact of selection bias in randomized multi-arm
parallel group clinical trials PLOS ONE, 13(1), 1-18.

See Also
Compute exact or simulated rejection probability: assess.
Other issues: chronBias, combineBias(), corGuess, imbal, issue, setPower()
70 setPower

Examples
# create a selection bias of the convergency strategy type with eta = 0.25 for which
# the exact rejection probabilities are calculated
sbias <- selBias("CS", 0.25, "exact")

setPower Representing the power

Description
Represents the expected power of the individual randomization sequences.

Usage
setPower(d, method, alpha = 0.05)

Arguments
d effect size.
method character string, should be one of "sim" or "exact", see Description.
alpha significance level.

Details
The attained power of an individual randomization sequence can be an issue in the design of a
clinical trial. The power of a randomization sequence is computed depending on the effect size d
and the difference in group sizes.
If method="sim", the object represents the simulated power of an individual randomization se-
quence. When calling assess for a power object with method="sim", one test decision is computed
for each randomization sequence of randSeq. The power is the proportion of falsely (correctly) re-
jected null hypotheses.
If method="exact", the object represents the exact power of an individual randomization sequence.
When calling assess for a power object with method="exact", the exact p-value of each random-
ization sequence is computed. So far, this is only supported for normal endpoints. Then the power
is the sum of the corresponding quantiles of the noncentral t-distribution.

Value
S4 object of class power, a formal representation of the issue of power in a clinical trial.

See Also
Other issues: chronBias, combineBias(), corGuess, imbal, issue, selBias
shape 71

shape Method returning the shape parameter of an survEndp S4 object

Description
Method returning the shape parameter of an survEndp S4 object

Usage
shape(obj)

Arguments
obj object of class survEndp

sigma Function returning the standard deviation slot of a normEndp S4 ob-

ject

Description
Function returning the standard deviation slot of a normEndp S4 object

Usage
sigma(obj)

Arguments
obj object of class normEndp

summary Summary of assessments of a randomization procedure

Description
Summary of assessments of a randomization procedure
Summary of desirability scores of a randomization procedure
72 summary

Usage
summary(object, ...)

## S4 method for signature 'assessment'

summary(object)

summary(object, ...)

## S4 method for signature 'desScores'

summary(object)

Arguments
object assessment object.
... additional arguments affecting the summary that will be produced.

Details
For each issue the assessment of the sequences is summarized to permit a design-based assessment
of the randomization procedure. This approach uses the sequence-wise values of the assessment
and the probabilities in order to give an overall summary.
For each issue the desirability score of the sequences is summarized to permit a design-based desir-
ability score of the randomization procedure. This approach uses the sequence-wise values of the
desirability and the probabilities in order to give an overall summary.

Value
Data frame with a summary of the assessment object.
Data frame with a summary of the desirability scores object.

Examples
# assess the full set of PBR(4)
seq <- getAllSeq(pbrPar(4))
issue <- corGuess("CS")
A <- assess(seq, issue)
summary(A)

# compute the desirability scores of the full set of PBR(4)

seq <- getAllSeq(pbrPar(4))
issue1 <- corGuess("CS")
issue2 <- corGuess("DS")
A <- assess(seq, issue1, issue2)
d1 <- derFunc(0.5, c(0.1, 0.8), c(1, 1))
d2 <- derFunc(0.1, 0.7, 2)
D <- getDesScores(A, d1, d2, weights = c(5/6, 1/6))
summary(D)
survEndp 73

survEndp Representation of survival endpoints

Description
Represents survival endpoints in clinical trials.

Usage
survEndp(
cenRate,
accrualTime = 0,
cenTime,
shape,
scale,
weights = c(0, 0),
maxcombo = FALSE
)

Arguments
cenRate exponential censoring rate in a survival study.
accrualTime duration of the accrual period in a survival study.
cenTime total duration of a survival study (maximum length of followup).
shape parameter of the Weibull distribution (must be positive)
scale parameter of the Weibull distribution (must be positive)
weights numeric specifying the weights used for the test. Unless specified an unweighted
test is conducted.
maxcombo logical specifying if the maxcombo test is used

Details
The survEnd function is a constructor function for an S4 object of the class survEnd representing
a survival endpoint in a clinical trial.

Value
A S4 object representing a survival endpoint in a clinical trial.

See Also
Compute exact or simulated type-I-error: assess.
Other endpoint types: expEndp, normEndp
74 TV

tbdPar Representing Truncated Binomal Design

Description
Represents the Truncated Binomial Design.

Usage
tbdPar(bc = N, groups = LETTERS[1:2])

Arguments
bc vector which contains the lengths k_1,...,k_l of each block. This means that
the vector bc will have one entry for each block.
groups character vector of labels for the different treatments.

Details
A fair coin is tossed until half of the patients have been assigned to one of the treatment arms.
Afterwards, the randomization list is filled with the other treatment.

Value
S4 object of the class tbdPar.

References
W. F. Rosenberger and J. M. Lachin (2002) Randomization in Clinical Trials. Wiley.

See Also
Other randomization procedures: abcdPar, bbcdPar, bsdPar, chenPar, crPar, createParam(),
ebcPar, gbcdPar, hadaPar, mpPar, pbrPar, rarPar, rpbrPar, rtbdPar, udPar

TV Function returning the target value slot of an S4 object

Description
Function returning the target value slot of an S4 object

Usage
TV(obj)
type 75

Arguments
obj object inheriting from derFunc

type Get type of an object

Description
Accesses the type slot of an S4 object

Usage
type(obj)

Arguments
obj a bias object (i.e. S4 object inheriting from bias)

Value
Character string specifying the type of bias obj represents, e.g. "linT" in case of chronological
bias.

udPar Representing Wei’s Urn Design

Description
Represents Wei’s Urn Design.

Usage
udPar(N, ini, add, groups = LETTERS[1:2])

Arguments
N integer for the total sample size of the trial.
ini integer representing the initial urn composition.
add integer representing the number of balls that are added to the urn in each step.
groups character vector of labels for the different treatments.

Details
An urn is filled with a number of ini balls of both of the treatments. Afterwards, a ball is drawn
randomly from the urn. Finally, add balls are added to the urn from the opposite treatment. This
procedure is repeated until N patients are assigned.
76 udPar

Value
S4 object of the class udPar.

References
L.J. Wei (1977) A Class of Designs for Sequential Clinical Trials. Journal of the American Statis-
tical Association, 72, 382-6.

See Also
Other randomization procedures: abcdPar, bbcdPar, bsdPar, chenPar, crPar, createParam(),
ebcPar, gbcdPar, hadaPar, mpPar, pbrPar, rarPar, rpbrPar, rtbdPar, tbdPar
Index

∗ desirability topics a, 5
derFunc, 19 abcdPar, 5, 9–11, 18, 19, 22, 25, 47, 51, 56,
evaluate, 22 61, 63, 65, 66, 74, 76
getDesScores, 37 analyse, 6
plotDes, 57 assess, 4, 7, 24, 37, 48, 53, 66, 68, 69, 73
plotEv, 58 assess,randSeq,endpoint-method
probUnDes, 59 (assess), 7
∗ endpoint types assess,randSeq,missing-method (assess),
expEndp, 24 7
normEndp, 52
survEndp, 73 bbcdPar, 6, 8, 10, 11, 18, 19, 22, 25, 47, 51,
∗ issues 56, 61, 63, 65, 66, 74, 76
chronBias, 12 blocks, 9
combineBias, 14 bsdPar, 6, 9, 10, 11, 18, 19, 22, 25, 47, 51, 56,
corGuess, 16 61, 63, 65, 66, 74, 76
imbal, 47
issue, 48 calcProb (getProbabilities), 41
selBias, 68 calculateProbabilities
setPower, 70 (getProbabilities), 41
∗ randomization procedures chenPar, 6, 9, 10, 11, 18, 19, 22, 25, 47, 51,
abcdPar, 5 56, 61, 63, 65, 66, 74, 76
bbcdPar, 8 chronBias, 12, 14, 17, 40, 47, 48, 69, 70
bsdPar, 10 coin, 13
chenPar, 11 combineBias, 13, 14, 17, 47, 48, 69, 70
createParam, 17 compare, 4, 15, 48, 57
crPar, 18 compare,issue,endpoint-method
ebcPar, 21 (compare), 15
gbcdPar, 25 compare,issue,missing-method (compare),
hadaPar, 46 15
mpPar, 50 corGuess, 13, 14, 16, 47, 48, 69, 70
pbrPar, 55 createParam, 6, 9–11, 17, 19, 22, 25, 27, 32,
rarPar, 62 43, 47, 51, 54, 56, 61, 63, 65, 66, 68,
rpbrPar, 64 74, 76
rtbdPar, 65 createSeq, 18
tbdPar, 74 crPar, 6, 9–11, 18, 18, 22, 25, 47, 51, 56, 61,
udPar, 75 63, 65, 66, 74, 76
∗ saving functions
saveAssess, 66 derFunc, 19, 20, 23, 37, 57, 58, 60
saveRand, 67 desirability, 20

77
78 INDEX

ebcPar, 6, 9–11, 18, 19, 21, 25, 47, 51, 56, 61, genSeq,crPar,missing,numeric-method
63, 65, 66, 74, 76 (generateRandomSequences), 28
evaluate, 20, 22, 37, 57, 58, 60 genSeq,crPar,numeric,missing-method
evaluate,character-method (evaluate), 22 (generateRandomSequences), 28
evaluate,missing-method (evaluate), 22 genSeq,crPar,numeric,numeric-method
expEndp, 24, 53, 73 (generateRandomSequences), 28
genSeq,ebcPar,missing,missing-method
gbcdPar, 6, 9–11, 18, 19, 22, 25, 47, 51, 56, (generateRandomSequences), 28
61, 63, 65, 66, 74, 76 genSeq,ebcPar,missing,numeric-method
generateAllSequences, 26 (generateRandomSequences), 28
generateRandomSequences, 28 genSeq,ebcPar,numeric,missing-method
genNcps_new, 33 (generateRandomSequences), 28
genSeq, 4, 7, 15, 23, 37, 48, 60, 62 genSeq,ebcPar,numeric,numeric-method
genSeq (generateRandomSequences), 28 (generateRandomSequences), 28
genSeq,abcdPar,missing,missing-method genSeq,gbcdPar,missing,missing-method
(generateRandomSequences), 28 (generateRandomSequences), 28
genSeq,abcdPar,missing,numeric-method genSeq,gbcdPar,missing,numeric-method
(generateRandomSequences), 28 (generateRandomSequences), 28
genSeq,abcdPar,numeric,missing-method genSeq,gbcdPar,numeric,missing-method
(generateRandomSequences), 28 (generateRandomSequences), 28
genSeq,abcdPar,numeric,numeric-method genSeq,gbcdPar,numeric,numeric-method
(generateRandomSequences), 28 (generateRandomSequences), 28
genSeq,bbcdPar,missing,missing-method genSeq,hadaPar,missing,missing-method
(generateRandomSequences), 28 (generateRandomSequences), 28
genSeq,bbcdPar,missing,numeric-method genSeq,hadaPar,missing,numeric-method
(generateRandomSequences), 28 (generateRandomSequences), 28
genSeq,bbcdPar,numeric,missing-method genSeq,hadaPar,numeric,missing-method
(generateRandomSequences), 28 (generateRandomSequences), 28
genSeq,bbcdPar,numeric,numeric-method genSeq,hadaPar,numeric,numeric-method
(generateRandomSequences), 28 (generateRandomSequences), 28
genSeq,bsdPar,missing,missing-method genSeq,mpPar,missing,missing-method
(generateRandomSequences), 28 (generateRandomSequences), 28
genSeq,bsdPar,missing,numeric-method genSeq,mpPar,missing,numeric-method
(generateRandomSequences), 28 (generateRandomSequences), 28
genSeq,bsdPar,numeric,missing-method genSeq,mpPar,numeric,missing-method
(generateRandomSequences), 28 (generateRandomSequences), 28
genSeq,bsdPar,numeric,numeric-method genSeq,mpPar,numeric,numeric-method
(generateRandomSequences), 28 (generateRandomSequences), 28
genSeq,chenPar,missing,missing-method genSeq,pbrPar,missing,missing-method
(generateRandomSequences), 28 (generateRandomSequences), 28
genSeq,chenPar,missing,numeric-method genSeq,pbrPar,missing,numeric-method
(generateRandomSequences), 28 (generateRandomSequences), 28
genSeq,chenPar,numeric,missing-method genSeq,pbrPar,numeric,missing-method
(generateRandomSequences), 28 (generateRandomSequences), 28
genSeq,chenPar,numeric,numeric-method genSeq,pbrPar,numeric,numeric-method
(generateRandomSequences), 28 (generateRandomSequences), 28
genSeq,crPar,missing,missing-method genSeq,rarPar,missing,missing-method
(generateRandomSequences), 28 (generateRandomSequences), 28
INDEX 79

genSeq,rarPar,missing,numeric-method (generateAllSequences), 26
(generateRandomSequences), 28 getAllSeq,crPar-method
genSeq,rarPar,numeric,missing-method (generateAllSequences), 26
(generateRandomSequences), 28 getAllSeq,ebcPar-method
genSeq,rarPar,numeric,numeric-method (generateAllSequences), 26
(generateRandomSequences), 28 getAllSeq,gbcdPar-method
genSeq,rpbrPar,missing,missing-method (generateAllSequences), 26
(generateRandomSequences), 28 getAllSeq,hadaPar-method
genSeq,rpbrPar,missing,numeric-method (generateAllSequences), 26
(generateRandomSequences), 28 getAllSeq,mpPar-method
genSeq,rpbrPar,numeric,missing-method (generateAllSequences), 26
(generateRandomSequences), 28 getAllSeq,pbrPar-method
genSeq,rpbrPar,numeric,numeric-method (generateAllSequences), 26
(generateRandomSequences), 28 getAllSeq,rarPar-method
genSeq,rtbdPar,missing,missing-method (generateAllSequences), 26
(generateRandomSequences), 28 getAllSeq,tbdPar-method
genSeq,rtbdPar,missing,numeric-method (generateAllSequences), 26
(generateRandomSequences), 28 getAllSeq,udPar-method
genSeq,rtbdPar,numeric,missing-method (generateAllSequences), 26
(generateRandomSequences), 28 getCorGuesses, 33
genSeq,rtbdPar,numeric,numeric-method getDesFunc, 34
(generateRandomSequences), 28 getDesFunc,derringerLs-method
genSeq,tbdPar,missing,missing-method (getDesFunc), 34
(generateRandomSequences), 28 getDesFunc,derringerRs-method
genSeq,tbdPar,missing,numeric-method (getDesFunc), 34
(generateRandomSequences), 28 getDesFunc,derringerTs-method
genSeq,tbdPar,numeric,missing-method (getDesFunc), 34
(generateRandomSequences), 28 getDesign, 34
genSeq,tbdPar,numeric,numeric-method getDesign,abcdPar-method (getDesign), 34
(generateRandomSequences), 28 getDesign,abcdSeq-method (getDesign), 34
genSeq,udPar,missing,missing-method getDesign,bbcdPar-method (getDesign), 34
(generateRandomSequences), 28 getDesign,bbcdSeq-method (getDesign), 34
genSeq,udPar,missing,numeric-method getDesign,bsdPar-method (getDesign), 34
(generateRandomSequences), 28 getDesign,bsdSeq-method (getDesign), 34
genSeq,udPar,numeric,missing-method getDesign,chenPar-method (getDesign), 34
(generateRandomSequences), 28 getDesign,chenSeq-method (getDesign), 34
genSeq,udPar,numeric,numeric-method getDesign,crPar-method (getDesign), 34
(generateRandomSequences), 28 getDesign,crSeq-method (getDesign), 34
get_p_values_new, 43 getDesign,ebcPar-method (getDesign), 34
getAllSeq, 7, 62 getDesign,ebcSeq-method (getDesign), 34
getAllSeq (generateAllSequences), 26 getDesign,gbcdPar-method (getDesign), 34
getAllSeq,abcdPar-method getDesign,gbcdSeq-method (getDesign), 34
(generateAllSequences), 26 getDesign,hadaPar-method (getDesign), 34
getAllSeq,bbcdPar-method getDesign,hadaSeq-method (getDesign), 34
(generateAllSequences), 26 getDesign,mpPar-method (getDesign), 34
getAllSeq,bsdPar-method getDesign,mpSeq-method (getDesign), 34
(generateAllSequences), 26 getDesign,pbrPar-method (getDesign), 34
getAllSeq,chenPar-method getDesign,pbrSeq-method (getDesign), 34
80 INDEX

getDesign,rarPar-method (getDesign), 34 (getExpectation), 39

getDesign,rarSeq-method (getDesign), 34 getExpectation,randSeq,missing,expEndp-method
getDesign,rpbrPar-method (getDesign), 34 (getExpectation), 39
getDesign,rRpbrSeq-method (getDesign), getExpectation,randSeq,missing,normEndp-method
34 (getExpectation), 39
getDesign,rRtbdSeq-method (getDesign), getExpectation,randSeq,missing,survEndp-method
34 (getExpectation), 39
getDesign,rtbdPar-method (getDesign), 34 getExpectation,randSeq,power,normEndp-method
getDesign,tbdPar-method (getDesign), 34 (getExpectation), 39
getDesign,tbdSeq-method (getDesign), 34 getExpectation,randSeq,selBias,expEndp-method
getDesign,udPar-method (getDesign), 34 (getExpectation), 39
getDesign,udSeq-method (getDesign), 34 getExpectation,randSeq,selBias,missing-method
getDesScores, 20, 23, 37, 57, 58, 60 (getExpectation), 39
getDesScores,assessment,missing-method getExpectation,randSeq,selBias,normEndp-method
(getDesScores), 37 (getExpectation), 39
getDesScores,assessment,numeric-method getExpectation,randSeq,selBias,survEndp-method
(getDesScores), 37 (getExpectation), 39
getDistributionPars, 38 getProb (getProbabilities), 41
getProb,abcdSeq-method
getDistributionPars,randSeq,chronBias,survEndp-method
(getDistributionPars), 38 (getProbabilities), 41
getProb,bbcdSeq-method
getDistributionPars,randSeq,combinedBias,survEndp-method
(getDistributionPars), 38 (getProbabilities), 41
getProb,bsdSeq-method
getDistributionPars,randSeq,combinedBiasStepTrend,survEndp-method
(getDistributionPars), 38 (getProbabilities), 41
getProb,chenSeq-method
getDistributionPars,randSeq,missing,survEndp-method
(getDistributionPars), 38 (getProbabilities), 41
getProb,crSeq-method
getDistributionPars,randSeq,selBias,survEndp-method
(getDistributionPars), 38 (getProbabilities), 41
getExpectation, 39 getProb,ebcSeq-method
getExpectation,randSeq,chronBias,expEndp-method (getProbabilities), 41
(getExpectation), 39 getProb,gbcdSeq-method
getExpectation,randSeq,chronBias,missing-method (getProbabilities), 41
(getExpectation), 39 getProb,hadaSeq-method
getExpectation,randSeq,chronBias,normEndp-method (getProbabilities), 41
(getExpectation), 39 getProb,mpSeq-method
getExpectation,randSeq,chronBias,survEndp-method (getProbabilities), 41
(getExpectation), 39 getProb,pbrSeq-method
getExpectation,randSeq,combinedBias,expEndp-method (getProbabilities), 41
(getExpectation), 39 getProb,rarSeq-method
getExpectation,randSeq,combinedBias,normEndp-method (getProbabilities), 41
(getExpectation), 39 getProb,tbdSeq-method
getExpectation,randSeq,combinedBias,survEndp-method (getProbabilities), 41
(getExpectation), 39 getProb,udSeq-method
getExpectation,randSeq,combinedBiasStepTrend,expEndp-method
(getProbabilities), 41
(getExpectation), 39 getProbabilities, 41
getRandList (getRandomizationList), 42
getExpectation,randSeq,combinedBiasStepTrend,normEndp-method
(getExpectation), 39 getRandomizationList, 42
getExpectation,randSeq,combinedBiasStepTrend,survEndp-method
GSD_allocation, 44
INDEX 81

GSD_allocation_seq, 45 rpbrPar, 6, 9–11, 18, 19, 22, 25, 47, 51, 56,
61, 63, 64, 66, 74, 76
hadaPar, 6, 9–11, 18, 19, 22, 25, 46, 51, 56, rtbdPar, 6, 9–11, 18, 19, 22, 25, 47, 51, 56,
61, 63, 65, 66, 74, 76 61, 63, 65, 65, 74, 76

imbal, 13, 14, 17, 47, 48, 69, 70 saveAssess, 66, 67

issue, 13, 14, 17, 47, 48, 69, 70 saveRand, 66, 67
issues, 4, 7, 15, 23, 37, 60 scale, 67
issues (issue), 48 seed, 68
selBias, 13, 14, 17, 40, 47, 48, 68, 70
K, 49 setPower, 13, 14, 17, 47, 48, 69, 70
shape, 71
lambda, 49 sigma, 71
summary, 71
method, 50
summary,assessment-method (summary), 71
mpPar, 6, 9–11, 18, 19, 22, 25, 47, 50, 56, 61,
summary,desScores-method (summary), 71
63, 65, 66, 74, 76
survEndp, 24, 53, 73
mti, 51
mu, 51 tbdPar, 6, 9–11, 18, 19, 22, 25, 47, 51, 56, 61,
63, 65, 66, 74, 76
N, 52
TV, 74
normEndp, 24, 40, 52, 73
type, 75
overview, 53
udPar, 6, 9–11, 18, 19, 22, 25, 47, 51, 56, 61,
63, 65, 66, 74, 75
pbrPar, 6, 9–11, 18, 19, 22, 25, 47, 51, 55, 61,
63, 65, 66, 74, 76
plot, 56
plot,comparison,character-method
(plot), 56
plot,comparison,missing-method (plot),
56
plotDes, 20, 23, 37, 57, 58, 60
plotEv, 20, 23, 37, 57, 58, 60
plotSeq, 59
probUnDes, 20, 23, 37, 57, 58, 59
probUnDes,desScores-method (probUnDes),
59

randBlocks, 61
randomizeR (randomizeR-package), 4
randomizeR-package, 4
randPar, 4, 7, 15, 17, 23, 27, 32, 37, 43, 48,
54, 60, 61, 68
randSeq, 27, 32
randSeq-class, 62
rarPar, 6, 9–11, 18, 19, 22, 25, 47, 51, 56, 61,
62, 65, 66, 74, 76
ratio, 63
rho, 64