SimTOST: Sample Size Estimation for Bio-Equivalence Trials Through Simulation

Sample size estimation for bio-equivalence trials is supported through a simulation-based approach that extends the Two One-Sided Tests (TOST) procedure. The methodology provides flexibility in hypothesis testing, accommodates multiple treatment comparisons, and accounts for correlated endpoints. Users can model complex trial scenarios, including parallel and crossover designs, intra-subject variability, and different equivalence margins. Monte Carlo simulations enable accurate estimation of power and type I error rates, ensuring well-calibrated study designs. The statistical framework builds on established methods for equivalence testing and multiple hypothesis testing in bio-equivalence studies, as described in Schuirmann (1987) <doi:10.1007/BF01068419>, Mielke et al. (2018) <doi:10.1080/19466315.2017.1371071>, Shieh (2022) <doi:10.1371/journal.pone.0269128>, and Sozu et al. (2015) <doi:10.1007/978-3-319-22005-5>. Comprehensive documentation and vignettes guide users through implementation and interpretation of results.

Version: 1.1.0
Imports: MASS, Rcpp (≥ 1.0.13), data.table, matrixcalc, parallel
LinkingTo: Rcpp, RcppArmadillo
Suggests: ggplot2, kableExtra, knitr, rmarkdown, scales, testthat (≥ 3.0.0), tibble
Published: 2026-10-09
DOI: 10.32614/CRAN.package.SimTOST
Author: Thomas Debray [aut, cre], Tim Friede [ctb], Johanna Munoz [ctb], Dewi Amaliah [ctb], Wei Wei [ctb], Marian Mitroiu [ctb], Scott McDonald [ctb], Biogen Inc [cph, fnd] (Copyright holder and funder of the original implementation v1.0.0), Smart Data Analysis and Statistics B.V. [cph, fnd] (Copyright holder and funder of subsequent developments)
Maintainer: Thomas Debray <tdebray at fromdatatowisdom.com>
BugReports: https://github.com/smartdata-analysis-and-statistics/SimTOST/issues
License: Apache License (≥ 2)
URL: https://smartdata-analysis-and-statistics.github.io/SimTOST/, https://github.com/smartdata-analysis-and-statistics/SimTOST
NeedsCompilation: yes
Materials: README, NEWS
CRAN checks: SimTOST results

Documentation:

Reference manual: SimTOST.html , SimTOST.pdf
Vignettes: Bioequivalence Tests for 2x2 Cross-Over Trial Designs with Log-Normal Data (source, R code)
Bioequivalence Tests for Parallel Trial Designs with Log-Normal Data (source, R code)
Bioequivalence Tests for Parallel Trial Designs: 2 Arms, 1 Endpoint (source, R code)
Bioequivalence Tests for Parallel Trial Designs: 2 Arms, 3 Endpoints (source, R code)
Bioequivalence Tests for Parallel Trial Designs: 3 Arms, 1 Endpoint (source, R code)
Bioequivalence Tests for Parallel Trial Designs: 3 Arms, 3 Endpoints (source, R code)
Count Outcomes (source, R code)
Count-Outcome Equivalence: Parallel Design with 3 Arms and 3 Endpoints (source, R code)
Introduction (source, R code)
Methodological Assumptions in SimTOST (source, R code)
A Step-by-Step Simulation Validation Workflow (source, R code)

Downloads:

Package source: SimTOST_1.1.0.tar.gz
Windows binaries: r-devel: SimTOST_1.0.2.zip, r-release: SimTOST_1.0.2.zip, r-oldrel: SimTOST_1.0.2.zip
macOS binaries: r-release (arm64): SimTOST_1.1.0.tgz, r-oldrel (arm64): SimTOST_1.1.0.tgz, r-release (x86_64): SimTOST_1.1.0.tgz, r-oldrel (x86_64): SimTOST_1.1.0.tgz
Old sources: SimTOST archive

Linking:

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