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.
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")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 |
|---|---|---|---|
| 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 |
| 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 |