RSABE with two test products [Design Issues]
❝ When design a crossover trial with two test drug (or one ODT given with/without water), I run into confusion about how to give a balanced design for the trial.
If the design is not reference-replicated, easy. See this article.
❝ Furthermore, which make things even worse, I always get confused by "variance-balanced" and "carryover-balance" design.
True unequal carryover will bias the treatment effect. It cannot be “corrected” statistically. It can only be avoided by sufficiently long washouts. See this article. Carryover is not included in the current models for BE. Since sample sizes for a conventional Latin Squares and (variance-balanced) Williams’ designs are similar,* you can use any of them.
❝ I came out with the following design, but I'm not sure if it is suitable to use when analyzed with FDA RSABE approach.
T1 R T2 R
R T1 R T2
T2 R T1 R
R T2 R T1
First of all you have to receive a positive statement from the FDA in a “Controlled Correspondence” because this is not one of the recommended designs for RSABE.
According to ICH M13A you have to exclude treatments (
T2) and perform two separate analyses on the respective others (
R). Your design will lead to two partial replicate designs with missing observations (denoted with
T1 R • R
R T1 R •
• R T1 R
R • R T1
• R T2 R
R • R T2
T2 R • R
R T2 R •
- For 4-treatments the sample size is equal in Latin Squares and one of the six possible Williams’ designs.
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- crossover design when use RSABE with two test products Darborn 2023-08-22 02:24 [Design Issues]