Blinded Sample Size Recalculation.

blindrecalc

blindrecalc facilitates the planning of a clinical trial with an internal pilot study and blinded sample size recalculation.

Installation

Install the current CRAN version of blindrecalc with:

install.packages("blindrecalc")

Or install the development version from GitHub with:

# install.packages("devtools")
devtools::install_github("imbi-heidelberg/blindrecalc")

Usage

blindrecalc currently supports continuous and binary endpoints for superiority and non-inferiority test problems. Continuous endpoints are analyzed using Student’s t-test, binary endpoints are analyzed using the Chi-squared test for superiority trials and the Farrington-Manning test for non-inferiority trials. Each design can be defined using a setup-function: setupStudent, setupChiSquare and setupFarringtonManning. For example, to setup a superiority trial with a continuous endpoint:

library(blindrecalc)
design <- setupStudent(alpha = 0.025, beta = 0.2, r = 1, delta = 5)

alpha and beta refer to the type 1 and type 2 error rate, r is the sample size allocation ratio and deltais the effect size between the null and the alternative hypothesis. For a non-inferiority trial with a shifted t-test, additionally the argument delta_NI must be specified.

To calculate the sample size for a fixed design, use n_fix:

n_fix(design, nuisance = c(5, 10, 15))
#> [1]  31.39552 125.58208 282.55967

nuisance refers to the nuisance parameter of the design, which in the case of the t-test is the common variance of the outcome variable.

To calculate the type 1 error rate of the design using blinded sample size recalculation, use toer:

toer(design, n1 = c(30, 60, 90), nuisance = 10, recalculation = TRUE)
#> [1] 0.0259 0.0235 0.0252

n1 refers to the sample size of the internal pilot study recalculation = TRUE specifices that the type 1 error rate for a design with blinded sample size recalculation should be computed.

To compute the power of the design, use pow:

pow(design, n1 = c(30, 60, 90), nuisance = 10, recalculation = TRUE)
#> [1] 0.7877 0.8039 0.8056

To calculate the distribution of the total sample sizes use n_dist:

n_dist(design, n1 = c(30, 60, 90), nuisance = 10)
#>     n_1 = 30        n_1 = 60      n_1 = 90    
#>  Min.   : 36.0   Min.   : 63   Min.   : 90.0  
#>  1st Qu.:109.0   1st Qu.:117   1st Qu.:120.0  
#>  Median :131.0   Median :132   Median :133.0  
#>  Mean   :134.1   Mean   :134   Mean   :134.5  
#>  3rd Qu.:155.0   3rd Qu.:150   3rd Qu.:147.0  
#>  Max.   :322.0   Max.   :282   Max.   :223.0

Reference

A paper describing blindrecalc can be found here.