What is the purpose? [Design Issues]
Hi M.tareq,
Can you give us an example how the sequences would look like? What is the purpose of having two Test-products in the study? See also this post and followings.
No it isn’t. The FDA recommends two conventional 2×2×2 studies (fasting and fed state).
According to the WHO’s PQTm the reference in fed state is a HVDP (Cmax CVwR 54%) whilst variability of AUC is low (CVwR 10%). In the WHO’s guidance reference-scaling for Cmax according to the EMA’s method is mentioned as an alternative.
I have never heard about such a design.
No idea.
The sequence effect is confounded with
You mentioned Sas proc mixed in the subject line. If you want to apply the EMA’s ABEL, a mixed-effects model is not acceptable. If you want to apply the FDA’s RSABE, the partial replicate for the unscaled PK metric (AUC) may fail to converge. Specify the covariance structure with
❝ […] performing stat analysis of a 4 period 4 seq 3 treatment partial replicate Cross over study, where the ref product only replicate against t1 and t2 for a bioequivlence study of sofosbuvir?
Can you give us an example how the sequences would look like? What is the purpose of having two Test-products in the study? See also this post and followings.
❝ The FDA recommendation is for full replicate…
No it isn’t. The FDA recommends two conventional 2×2×2 studies (fasting and fed state).
According to the WHO’s PQTm the reference in fed state is a HVDP (Cmax CVwR 54%) whilst variability of AUC is low (CVwR 10%). In the WHO’s guidance reference-scaling for Cmax according to the EMA’s method is mentioned as an alternative.
❝ …and there are little information found regarding a 4 period Cross over with partial replication?
I have never heard about such a design.
❝ What other effects to account for beside the usual fixed effects in traditional 2x2 Cross over?
No idea.
❝ Within subject effect, within formulation variability, and carry over effect?
The sequence effect is confounded with
- the carry-over effect, and
- the formulation-by-period interaction.
- a true sequence effect,
- a true carry-over effect,
- a true formulation-by-period interaction, or
- a failure of randomization.
❝ Newbie in stat...
You mentioned Sas proc mixed in the subject line. If you want to apply the EMA’s ABEL, a mixed-effects model is not acceptable. If you want to apply the FDA’s RSABE, the partial replicate for the unscaled PK metric (AUC) may fail to converge. Specify the covariance structure with
TYPE=FA0(1)
instead of TYPE=FA0(2)
as given in the progesterone guidance.—
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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:
- Sas proc mixed and 4 period partial replicate Cross over M.tareq 2016-05-03 11:35 [Design Issues]
- What is the purpose?Helmut 2016-05-03 12:43
- What is the purpose? M.tareq 2016-05-03 15:06
- Alpha inflation ? Ohlbe 2016-05-03 15:48
- Alpha inflation d_labes 2016-05-03 16:06
- Not with such a high CV Helmut 2016-05-03 17:49
- High CV? d_labes 2016-05-03 21:07
- Acc. to WHO PQTm Helmut 2016-05-03 21:58
- Sofosbuvir d_labes 2016-05-04 11:50
- Acc. to WHO PQTm Helmut 2016-05-03 21:58
- High CV? d_labes 2016-05-03 21:07
- What is the purpose?Helmut 2016-05-03 12:43