SimTOST is an R package specifically designed for bioequivalence studies, providing simulation-based sample size estimation for the Two One-Sided Tests (TOST) procedure. It offers flexible options to handle complex study designs, including trials with multiple correlated primary endpoints, multiple hypotheses, and treatment arms. Multiplicity adjustments include Bonferroni (adjust = "bon"), Sidak (adjust = "sid"), the weak k-adjustment (adjust = "k"), Mielke’s strong k-out-of-m adjustment (adjust = "t"), and sequential hierarchical testing (adjust = "seq"). By incorporating correlations between endpoints, SimTOST ensures accurate and robust planning of bioequivalence trials, making it a powerful tool for studies with intricate requirements.
Installation
SimTOST is available on CRAN and can be installed by running the following code.
install.packages("SimTOST")You can also install the development version of SimTOST from GitHub with:
# install.packages("devtools")
devtools::install_github("smartdata-analysis-and-statistics/SimTOST")Vignettes
The main features of this package is sampleSize function which can be used to calculate sample size for individual and multiple endpoints. Various worked examples are available as vignettes, with an introduction provided at Introduction. The Introduction vignette describes the available multiplicity adjustments, including Mielke’s strong k-out-of-m adjustment (adjust = "t").
| Vignette | Design | Number of Arms | Number of Endpoints |
|---|---|---|---|
| Introduction | All supported designs | Varies | Varies |
| Methodological Assumptions in SimTOST | All supported designs | Varies | Varies |
| A Step-by-Step Simulation Validation Workflow | All supported designs | Varies | Varies |
| Bioequivalence Tests for Parallel Trial Designs with Log-Normal Data | Parallel | 2 | Multiple (e.g., 2 or 3) |
| Bioequivalence Tests for 2x2 Cross-Over Trial Designs with Log-Normal Data | Cross-over | 2 | 2 |
| Bioequivalence Tests for Parallel Trial Designs: 2 Arms, 1 Endpoint | Parallel | 2 | 1 |
| Bioequivalence Tests for Parallel Trial Designs: 3 Arms, 1 Endpoint | Parallel | 3 | 1 |
| Bioequivalence Tests for Parallel Trial Designs: 2 Arms, 3 Endpoints | Parallel | 2 | 3 |
| Bioequivalence Tests for Parallel Trial Designs: 3 Arms, 3 Endpoints | Parallel | 3 | 3 |
| Count Outcomes | Parallel and 2x2 crossover | 2 | 1 or more |
| Count-Outcome Equivalence: Parallel Design with 3 Arms and 3 Endpoints | Parallel | 3 | 3 |
