rpact: Confirmatory Adaptive Clinical Trial Design, Simulation, and Analysis

A validated, open source, free-of-charge R software package

rpact is a comprehensive validated, open source, free-of-charge R software package for:

• Clinical trial planning
• Clinical trial design evaluation and simulation
• Clinical trial data analysis

Functional Range

• Fixed sample design and designs with interim analysis stages
• Sample size and power calculation for
  • means (continuous endpoint)
  • rates (binary endpoint)
  • survival trials with flexible recruitment and survival time options
  • count data
• Simulation tool for means, rates, survival data, and count data
  • Assessment of adaptive sample size/event number recalculations based on conditional power
  • Assessment of treatment selection strategies in multi-arm trials
• Adaptive analysis of means, rates, and survival data
• Adaptive designs and analysis for multi-arm trials
• Adaptive analysis and simulation tools for enrichment design testing means, rates, and hazard ratios
• Automatic boundary recalculations during the trial for analysis with alpha spending approach, including under- and over-running

Installation

Installation from CRAN

# The easiest way to get rpact is to install it from cran:
install.packages("rpact")

Installation of the Developer Version

To use a feature from the development version, you can install the development version of rpact from GitHub.

# install.packages("pak")
pak::pak("rpact-com/rpact")

Learn To Use rpact

We recommend three ways to learn how to use rpact:

1. Use the Shiny app “RPACT Cloud”: cloud.rpact.com
2. Use the rpact vignettes
3. Book a training: www.rpact.com/services

Vignettes

• The open access vignettes are hosted at www.rpact.org/vignettes
• The exclusive vignettes are hosted at www.rpact.com/vignettes

Online Help

The online documentation (help files) can be opened here: rpact-com.github.io/rpact/reference

Additionally there are two different pdf versions of the manual available:

• rpact_v4_2.1_quick_start_guide.pdf (recommended for beginners)
• rpact_v4_2.1_manual.pdf

Inline Help

# display the manual of the package
help(package = "rpact")

Getting Started

library(rpact)

# display the manual of the package
help(package = "rpact")

# create an inverse normal design with default parameters
design <- getDesignInverseNormal()

# take a look at the design and its default values
design

# create a summary ouput of the design
design |> 
    summary()

# display the design characteristics
design |>
    getDesignCharacteristics()

# plot the design with default type 1 (Boundary Plot)
design |>
    plot()

# create an 'Average Sample Size and Power / Early Stop' plot
design |>
    plot(type = 6, nMax = 12)

Working with datasets

# create a group sequential design
design <- getDesignGroupSequential(
    kMax = 4, 
    alpha = 0.025,
    informationRates = c(0.2, 0.5, 0.8, 1),
    futilityBounds = rep(0.5244, 4 - 1),
    typeOfDesign = "WT", 
    deltaWT = 0.45
)

# take a look at the design
design

# create a dataset of means
data <- getDataset(
    n1     = c( 22,  11, 22,  11),
    n2     = c( 22,  13, 22,  13),
    means1 = c(  1, 1.1,  1,   1),
    means2 = c(1.4, 1.5,  3, 2.5),
    stDev1 = c(  1,   2,  2, 1.3),
    stDev2 = c(  1,   2,  2, 1.3)
)

# display the stage results
design |>
    getStageResults(dataInput = data, stage = 3)

# display the analysis results
design |>
    getAnalysisResults(
        dataInput = data, 
        equalVariances = TRUE,
        stage = 2, 
        nPlanned = c(10, 10),
        thetaH0 = 0, 
        thetaH1 = 1.3, 
        allocationRatioPlanned = 2
    )

User Concept

Workflow

• Everything is starting with a design, e.g.: design <- getDesignGroupSequential()
• Find the optimal design parameters with help of rpact comparison tools: getDesignSet
• Calculate the required sample size, e.g.: getSampleSizeMeans(), getPowerMeans()
• Simulate specific characteristics of an adaptive design, e.g.: getSimulationMeans()
• Collect your data, import it into R and create a dataset: data <- getDataset()
• Analyze your data: getAnalysisResults(design, data)

Focus on Usability

The most important rpact functions have intuitive names:

• getDesign[GroupSequential/InverseNormal/Fisher]()
• getDesignCharacteristics()
• getSampleSize[Means/Rates/Survival/Counts]()
• getPower[Means/Rates/Survival/Counts]()
• getSimulation[MultiArm/Enrichment][Means/Rates/Survival]()
• getDataSet()
• getAnalysisResults()
• getStageResults()

RStudio / Eclipse: auto code completion makes it easy to use these functions.

R generics

In general, everything runs with the R standard functions which are always present in R: so-called R generics, e.g., print, summary, plot, as.data.frame, names, length

Utilities

Several utility functions are available, e.g.

• getAccrualTime()
• getPiecewiseSurvivalTime()
• getNumberOfSubjects()
• getEventProbabilities()
• getPiecewiseExponentialDistribution()
• survival helper functions for conversion of pi, lambda and median, e.g., getLambdaByMedian()
• testPackage(): installation qualification on a client computer or company server (via unit tests)

RPACT Connect

Connecting you to insights, downloads, and premium support: connect.rpact.com

Validation

Please contact us to learn how to use rpact on FDA/GxP-compliant validated corporate computer systems and how to get a copy of the formal validation documentation that is customized and licensed for exclusive use by your company, e.g., to fulfill regulatory requirements.

About

• rpact is a comprehensive validated¹ R package for clinical research which
  • enables the design and analysis of confirmatory adaptive group sequential designs
  • is a powerful sample size calculator
  • is a free of charge open-source software licensed under LGPL-3
  • particularly, implements the methods described in the recent monograph by Wassmer and Brannath (2016)

For more information please visit www.rpact.com/products

• RPACT is a company which offers
  • enterprise software development services
  • technical support for the rpact package
  • consultancy and user training for clinical research using R
  • validated software solutions and R package development for clinical research

For more information please visit www.rpact.com/services

Contact

• For general requests please send an email to
• Please send your support request to
• Or use our contact form at www.rpact.com/contact

Bugs and Issues

Please use the github bug report form to submit bug descriptions and issues in a systematic way: github.com/rpact-com/rpact/issues

Recommended Vignette

Step-by-Step rpact Tutorial

Footnotes

1. The rpact validation documentation is available exclusively for our customers and supporting companies. For more information visit www.rpact.com/services/sla