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vignettes/sampleSize_parallel_2A3E.Rmd

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doc.cache <- T #for cran; change to F
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# Introduction
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In the `SimTOST` R package, which is specifically designed for sample size estimation for bioequivalence studies, hypothesis testing is based on the Two One-Sided Tests (TOST) procedure. [@sozu_sample_2015] In TOST, the equivalence test is framed as a comparison between the the null hypothesis of ‘new product is worse by a clinically relevant quantity’ and the alternative hypothesis of ‘difference between products is too small to be clinically relevant’. This vignette focuses on a parallel design, with 2 arms/treatments and 3 primary endpoints.
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# Introduction
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In many studies, the aim is to evaluate equivalence across multiple primary endpoints. The European Medicines Agency (EMA) recommends demonstrating bioequivalence for both **Area Under the Curve** (AUC) and **maximum concentration** (Cmax) when assessing pharmacokinetic properties. This vignette presents advanced techniques for calculating sample size in parallel trial designs involving three treatment arms and two endpoints.
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As an illustrative example, we consider published data from the phase-1 trial [NCT01922336](https://clinicaltrials.gov/study/NCT01922336#study-overview). This trial measured the pharmacokinetics (PK) of SB2 compared to its EU-sourced reference product (EU_Remicade). The following PK measures were reported following a single dose of SB2 or its EU reference product Remicade [@shin_randomized_2015]:

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