rpact (version 3.0.4)

getSimulationRates: Get Simulation Rates

Description

Returns the simulated power, stopping probabilities, conditional power, and expected sample size for testing rates in a one or two treatment groups testing situation.

Usage

getSimulationRates(
  design = NULL,
  ...,
  groups = 2L,
  normalApproximation = TRUE,
  riskRatio = FALSE,
  thetaH0 = ifelse(riskRatio, 1, 0),
  pi1 = seq(0.2, 0.5, 0.1),
  pi2 = NA_real_,
  plannedSubjects = NA_real_,
  directionUpper = TRUE,
  allocationRatioPlanned = NA_real_,
  minNumberOfSubjectsPerStage = NA_real_,
  maxNumberOfSubjectsPerStage = NA_real_,
  conditionalPower = NA_real_,
  pi1H1 = NA_real_,
  pi2H1 = NA_real_,
  maxNumberOfIterations = 1000L,
  seed = NA_real_,
  calcSubjectsFunction = NULL,
  showStatistics = FALSE
)

Arguments

design

The trial design. If no trial design is specified, a fixed sample size design is used. In this case, Type I error rate alpha, Type II error rate beta, twoSidedPower, and sided can be directly entered as argument where necessary.

...

Ensures that all arguments (starting from the "...") are to be named and that a warning will be displayed if unknown arguments are passed.

groups

The number of treatment groups (1 or 2), default is 2.

normalApproximation

The type of computation of the p-values. Default is FALSE for testing means (i.e., the t test is used) and TRUE for testing rates and the hazard ratio. For testing rates, if normalApproximation = FALSE is specified, the binomial test (one sample) or the exact test of Fisher (two samples) is used for calculating the p-values. In the survival setting normalApproximation = FALSE has no effect.

riskRatio

If TRUE, the design characteristics for one-sided testing of H0: pi1 / pi2 = thetaH0 are simulated, default is FALSE.

thetaH0

The null hypothesis value, default is 0 for the normal and the binary case (testing means and rates, respectively), it is 1 for the survival case (testing the hazard ratio). For non-inferiority designs, thetaH0 is the non-inferiority bound. That is, in case of (one-sided) testing of

• means: a value != 0 (or a value != 1 for testing the mean ratio) can be specified.

• rates: a value != 0 (or a value != 1 for testing the risk ratio pi1 / pi2) can be specified.

• survival data: a bound for testing H0: hazard ratio = thetaH0 != 1 can be specified.

For testing a rate in one sample, a value thetaH0 in (0, 1) has to be specified for defining the null hypothesis H0: pi = thetaH0.

pi1

A numeric value or vector that represents the assumed probability in the active treatment group if two treatment groups are considered, or the alternative probability for a one treatment group design, default is seq(0.2, 0.5, 0.1) (power calculations and simulations) or seq(0.4, 0.6, 0.1) (sample size calculations).

pi2

A numeric value that represents the assumed probability in the reference group if two treatment groups are considered, default is 0.2.

plannedSubjects

plannedSubjects is a vector of length kMax (the number of stages of the design) that determines the number of cumulated (overall) subjects when the interim stages are planned. For two treatment arms, it is the number of subjects for both treatment arms. For multi-arm designs, plannedSubjects refers to the number of subjects per selected active arm.

directionUpper

Specifies the direction of the alternative, only applicable for one-sided testing; default is TRUE which means that larger values of the test statistics yield smaller p-values.

allocationRatioPlanned

The planned allocation ratio n1 / n2 for a two treatment groups design, default is 1. For multi-arm designs, it is the allocation ratio relating the active arm(s) to the control.

minNumberOfSubjectsPerStage

When performing a data driven sample size recalculation, the vector minNumberOfSubjectsPerStage with length kMax determines the minimum number of subjects per stage (i.e., not cumulated), the first element is not taken into account. For two treatment arms, it is the number of subjects for both treatment arms. For multi-arm designs minNumberOfSubjectsPerStage refers to the minimum number of subjects per selected active arm.

maxNumberOfSubjectsPerStage

When performing a data driven sample size recalculation, the vector maxNumberOfSubjectsPerStage with length kMax determines the maximum number of subjects per stage (i.e., not cumulated), the first element is not taken into account. For two treatment arms, it is the number of subjects for both treatment arms. For multi-arm designs maxNumberOfSubjectsPerStage refers to the maximum number of subjects per selected active arm.

conditionalPower

If conditionalPower together with minNumberOfSubjectsPerStage and maxNumberOfSubjectsPerStage (or minNumberOfEventsPerStage and maxNumberOfEventsPerStage for survival designs) is specified, a sample size recalculation based on the specified conditional power is performed. It is defined as the power for the subsequent stage given the current data. By default, the conditional power will be calculated under the observed effect size. Optionally, you can also specify thetaH1 and stDevH1 (for simulating means), pi1H1 and pi2H1 (for simulating rates), or thetaH1 (for simulating hazard ratios) as parameters under which it is calculated and the sample size recalculation is performed.

pi1H1

If specified, the assumed probability in the active treatment group if two treatment groups are considered, or the assumed probability for a one treatment group design, for which the conditional power was calculated.

pi2H1

If specified, the assumed probability in the reference group if two treatment groups are considered, for which the conditional power was calculated.

maxNumberOfIterations

The number of simulation iterations, default is 1000.

seed

The seed to reproduce the simulation, default is a random seed.

calcSubjectsFunction

Optionally, a function can be entered that defines the way of performing the sample size recalculation. By default, sample size recalculation is performed with conditional power with specified minNumberOfSubjectsPerStage and maxNumberOfSubjectsPerStage (see details and examples).

showStatistics

If TRUE, summary statistics of the simulated data are displayed for the print command, otherwise the output is suppressed, default is FALSE.

Value

Returns a SimulationResults object. The following generics (R generic functions) are available for this object:

• names to obtain the field names,

• print to print the object,

• summary to display a summary of the object,

• plot to plot the object,

• as.data.frame to coerce the object to a data.frame,

• as.matrix to coerce the object to a matrix.

Simulation Data

The summary statistics "Simulated data" contains the following parameters: median [range]; mean +/-sd

$show(showStatistics = FALSE) or $setShowStatistics(FALSE) can be used to disable the output of the aggregated simulated data.

Example 1: simulationResults <- getSimulationRates(plannedSubjects = 40) simulationResults$show(showStatistics = FALSE)

Example 2: simulationResults <- getSimulationRates(plannedSubjects = 40) simulationResults$setShowStatistics(FALSE) simulationResults

getData can be used to get the aggregated simulated data from the object as data.frame. The data frame contains the following columns:

1. iterationNumber: The number of the simulation iteration.

2. stageNumber: The stage.

3. pi1: The assumed or derived event rate in the treatment group (if available).

4. pi2: The assumed or derived event rate in the control group (if available).

5. numberOfSubjects: The number of subjects under consideration when the (interim) analysis takes place.

6. rejectPerStage: 1 if null hypothesis can be rejected, 0 otherwise.

7. futilityPerStage: 1 if study should be stopped for futility, 0 otherwise.

8. testStatistic: The test statistic that is used for the test decision, depends on which design was chosen (group sequential, inverse normal, or Fisher combination test)'

9. testStatisticsPerStage: The test statistic for each stage if only data from the considered stage is taken into account.

10. overallRate1: The overall rate in treatment group 1.

11. overallRate2: The overall rate in treatment group 2.

12. stagewiseRates1: The stagewise rate in treatment group 1.

13. stagewiseRates2: The stagewise rate in treatment group 2.

14. sampleSizesPerStage1: The stagewise sample size in treatment group 1.

15. sampleSizesPerStage2: The stagewise sample size in treatment group 2.

16. trialStop: TRUE if study should be stopped for efficacy or futility or final stage, FALSE otherwise.

17. conditionalPowerAchieved: The conditional power for the subsequent stage of the trial for selected sample size and effect. The effect is either estimated from the data or can be user defined with pi1H1 and pi2H1.

How to get help for generic functions

Click on the link of a generic in the list above to go directly to the help documentation of the rpact specific implementation of the generic. Note that you can use the R function methods to get all the methods of a generic and to identify the object specific name of it, e.g., use methods("plot") to get all the methods for the plot generic. There you can find, e.g., plot.AnalysisResults and obtain the specific help documentation linked above by typing ?plot.AnalysisResults.

Details

At given design the function simulates the power, stopping probabilities, conditional power, and expected sample size at given number of subjects and parameter configuration. Additionally, an allocation ratio = n1/n2 can be specified where n1 and n2 are the number of subjects in the two treatment groups.

The definition of pi1H1 and/or pi2H1 makes only sense if kMax > 1 and if conditionalPower, minNumberOfSubjectsPerStage, and maxNumberOfSubjectsPerStage (or calcSubjectsFunction) are defined.

calcSubjectsFunction This function returns the number of subjects at given conditional power and conditional critical value for specified testing situation. The function might depend on variables stage, riskRatio, thetaH0, groups, plannedSubjects, sampleSizesPerStage, directionUpper, allocationRatioPlanned, minNumberOfSubjectsPerStage, maxNumberOfSubjectsPerStage, conditionalPower, conditionalCriticalValue, overallRate, farringtonManningValue1, and farringtonManningValue2. The function has to contain the three-dots argument '...' (see examples).

Examples

# NOT RUN {
# Fixed sample size design (two groups) with total sample 
# size 120, pi1 = (0.3,0.4,0.5,0.6) and pi2 = 0.3
getSimulationRates(pi1 = seq(0.3, 0.6, 0.1), pi2 = 0.3, 
    plannedSubjects = 120, maxNumberOfIterations = 10)
# }
# NOT RUN {
# Increase number of simulation iterations and compare results with power calculator
getSimulationRates(pi1 = seq(0.3, 0.6, 0.1), pi2 = 0.3, 
    plannedSubjects = 120, maxNumberOfIterations = 50)
getPowerRates(pi1 = seq(0.3, 0.6, 0.1), pi2 = 0.3, maxNumberOfSubjects = 120)

# Do the same for a two-stage Pocock inverse normal group sequential 
# design with non-binding futility stops
designIN <- getDesignInverseNormal(typeOfDesign = "P", futilityBounds = c(0))
getSimulationRates(designIN, pi1 = seq(0.3, 0.6, 0.1), pi2 = 0.3, 
    plannedSubjects = c(40, 80), maxNumberOfIterations = 50)
getPowerRates(designIN, pi1 = seq(0.3, 0.6, 0.1), pi2 = 0.3, maxNumberOfSubjects = 80)

# Assess power and average sample size if a sample size reassessment is 
# foreseen at conditional power 80% for the subsequent stage (decrease and increase) 
# based on observed overall rates and specified minNumberOfSubjectsPerStage 
# and maxNumberOfSubjectsPerStage

# Do the same under the assumption that a sample size increase only takes place 
# if the rate difference exceeds the value 0.1 at interim. For this, the sample 
# size recalculation method needs to be redefined:  
mySampleSizeCalculationFunction <- function(..., stage,
        plannedSubjects,
        minNumberOfSubjectsPerStage,
        maxNumberOfSubjectsPerStage,
        conditionalPower,
        conditionalCriticalValue,
        overallRate) {
    if (overallRate[1] - overallRate[2] < 0.1) {
        return(plannedSubjects[stage] - plannedSubjects[stage - 1]) 
    } else {
        rateUnderH0 <- (overallRate[1] + overallRate[2]) / 2 
        stageSubjects <- 2 * (max(0, conditionalCriticalValue * 
            sqrt(2 * rateUnderH0 * (1 - rateUnderH0)) + 
            stats::qnorm(conditionalPower) * sqrt(overallRate[1] * 
            (1 - overallRate[1]) + overallRate[2] * (1 - overallRate[2]))))^2 /
            (max(1e-12, (overallRate[1] - overallRate[2])))^2
        stageSubjects <- ceiling(min(max(
            minNumberOfSubjectsPerStage[stage], 
            stageSubjects), maxNumberOfSubjectsPerStage[stage]))
        return(stageSubjects)
    }
}
getSimulationRates(designIN, pi1 = seq(0.3, 0.6, 0.1), pi2 = 0.3, 
    plannedSubjects = c(40, 80), minNumberOfSubjectsPerStage = c(40, 20), 
    maxNumberOfSubjectsPerStage = c(40, 160), conditionalPower = 0.8, 
    calcSubjectsFunction = mySampleSizeCalculationFunction, maxNumberOfIterations = 50)
# }
# NOT RUN {
# }