Williams’ design (all at once vs. two-at-a-time) [Power / Sample Size]
Hi Irene,
Since you have to show BE for all PK metrics you should estimate the sample size based on the one which has the highest CV. Generally the order is Cmin > Cmax > partialAUC > AUC0–∞ > AUC0–t. If you would base it on the one of AUC you would compromise power for Cmax. If this is a single dose study try to get the CV of Cmax.
I would not use any of the published sample size tables anymore since
Depends. If you want to evaluate it “all at once”, i.e., use one pooled variance, no (different degrees of freedom in a 2×2×2 n–2 and in a 3×6×3 2n–4).
But remember our previous conversation. I suggest to use the “two-at-a-time” approach (i.e., perform two separate analyses T1 vs. R and T2 vs. R) instead. If you plan for that, you could estimate the sample size like a 2×2×2 crossover (see Detlew’s comment).
❝ […] sample size determination for conducting William Design (3 treatment - 3 period - 6 sequence) bioequivalence. […] the drug product we would like to compare has about 19.03% intra-subject CV for AUC.
Since you have to show BE for all PK metrics you should estimate the sample size based on the one which has the highest CV. Generally the order is Cmin > Cmax > partialAUC > AUC0–∞ > AUC0–t. If you would base it on the one of AUC you would compromise power for Cmax. If this is a single dose study try to get the CV of Cmax.
❝ Usually, we calculate the sample size by intra-subject CV from the previous study and referred to Diletti table […].
I would not use any of the published sample size tables anymore since
- only certain combinations of the assumed GMR, CV, and desired power are provided and
- power is a highly nonlinear function, making interpolation not a trivial task.
PowerTOST
are open source and free of cost.❝ Is that also applicable for the 3x3x6 study?
Depends. If you want to evaluate it “all at once”, i.e., use one pooled variance, no (different degrees of freedom in a 2×2×2 n–2 and in a 3×6×3 2n–4).
But remember our previous conversation. I suggest to use the “two-at-a-time” approach (i.e., perform two separate analyses T1 vs. R and T2 vs. R) instead. If you plan for that, you could estimate the sample size like a 2×2×2 crossover (see Detlew’s comment).
—
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Dif-tor heh smusma 🖖🏼 Довге життя Україна!
![[image]](https://static.bebac.at/pics/Blue_and_yellow_ribbon_UA.png)
Helmut Schütz
![[image]](https://static.bebac.at/img/CC by.png)
The quality of responses received is directly proportional to the quality of the question asked. 🚮
Science Quotes
Complete thread:
- Sample size determination for William Design Irene_I 2018-07-04 10:27 [Power / Sample Size]
- Williams’ design (all at once vs. two-at-a-time)Helmut 2018-07-04 11:32
- Williams’ design (all at once vs. two-at-a-time) Irene_I 2018-07-05 11:04
- Williams’ design (all at once vs. two-at-a-time)Helmut 2018-07-04 11:32