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posted by BEQool  – 2024-11-26 09:15 (5 d 09:21 ago) – Posting: # 24297
Views: 254
(edited on 2024-11-26 13:40)

Hello Helmut,

❝ Quite likely, esp. since agencies think that \(\small{p(G\times T)<0.05}\) is a signal of data manipulation.

In cases where we have "good" PEs for PK parameters (let's say PEs around 100%) in the first group and "bad" PEs for PK parameters (let's now say around 85% or 115%) in the second group, there should be no reason to question the data integrity right?

❝ ❝ ❝ A new term: Hardly overlapping CIs. Again: So what? Justification?

❝ ❝ How do you plan to "justify" this difference?

❝ Well, the deadline for the response is today. I made only sarcastic comments like …As long as confidence limits overlap, treatment effects estimated in the groups do not differ significantly. To question that is like saying “since the upper confidence limit is 124%, products are hardly bioequivalent”… and suggested the applicant to translate it into a more diplomatic language.

:-D:-D

❝ I forgot something. The GL states… applicants should evaluate potential for heterogeneity of treatment effect across groups …In my understanding »across groups« means all pairwise comparisons. Then their number increases quickly with the number of groups and PK metrics. Let \(\small{n}\) be the number of groups and \(\small{m}\) the number of PK-metrics. Then the number of pairwise comparisons is given by \(\small{k=}\frac{n!}{2\,(n-2)!}\) per metric. The familywise error rate (here the chance to observe at least one false positive in any of the tests) is given by \(\small{(1-(1-\alpha)^k})\times m\). With \(\small{\alpha=0.05}\) in my example above we get 10%. In order to counteract that we should test with \(\small{\alpha_\text{adj}=\alpha / (k\times m)}\).

❝ If that is done, the G×T interaction of Cmax would not be significant any more.

Well to me that sounds like a good answer to a deficiency letter as well :-)

PS How do you get FWER=10%? Based on your example above m=2 (AUC and Cmax), n=2 (2 groups) and therefore k=2. With alpha=0.05 shouldnt FWER be 19.5%?
Or did you use m=1 as both AUC and Cmax should be okay (union-intersection principle) and got FWER=9.75%=10%?

BEQool

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