Bioequivalence and Bioavailability Forum

Q&A ref [Two-Stage / GS Designs]

posted by Astea – Russia, 2019-09-16 20:28 (1847 d 16:21 ago) – Posting: # 20599
Views: 10,875

Dear Helmut!

❝ I was wrong and we shouldn’t worry. See Detlew’s simulations.

That's good. Sorry, I didn't realized it at first.

❝ How likely is it that AUC (which passed already in the first stage) will fail in the second?

Thank you for the example! I've puzzled whether it will be reproduced for other cases. Let us consider the situation when CV of C_max and AUC are very close to each other, like 21% and 20%, and for the first stage the number of subjects (n₁=20) was sufficient for AUC, but not for C_max.
Calculation shows that even then the power for AUC for the second stage would be always enough.

for(j in 5:100){nj1<-sampleN.TOST(CV=j/100,print=FALSE)[1,7]
n02<-sampleN2.TOST(CV=(j+1)/100,n1=nj1)[1,8]
nj2<-nj1+n02
print(suppressMessages(power.TOST(CV=j/100,n=nj2-1,alpha=0.0294)))}


❝ Take some Schützomycin?

Did you patent that? I gonna make a generic

❝ According to the Q&A:

stage, sequence, sequence × stage, subject(sequence × stage), period(stage), treatment.

Are there any documents to refer which mention this model (excepting the answer on the EMA's web page?)

❝ Ask Detlew or inspect the sources of power.tsd() and power.tsd.2m().

Ok, need more tea to dive to the source...

Complete thread:

• Appropriate wording for a protocol Elena777 2019-09-09 19:34 [Two-Stage / GS Designs] 
  • Appropriate wording for a protocol ElMaestro 2019-09-09 21:39
    • Appropriate wording for a protocol Helmut 2019-09-09 23:27
    • Appropriate wording for a protocol Ohlbe 2019-09-10 10:27
  • Which country? Helmut 2019-09-09 23:17
    • Which country? Elena777 2019-09-11 20:24
      • EEU-rules, TSD-methods (lengthy answer) Helmut 2019-09-12 01:31
        • EEU-rules, TSD-methods (lengthy question) Astea 2019-09-14 14:56
          • n2 based on PK metric with higher CV Helmut 2019-09-16 11:50
            • Q&A refAstea 2019-09-16 18:28
              • The omniscient oracle has spoken Helmut 2019-09-17 12:27
                • The omniscient oracle has spoken Astea 2019-09-17 20:34
                  • OT: Булга́ков Helmut 2019-09-18 12:12
            • n2 based on PK metric with higher CV Elena777 2019-09-16 19:48
              • AUC passes with 0.05 and Cmax with 0.0294 Helmut 2019-09-16 23:30
                • AUC passes with 0.05 and Cmax with 0.0294 Mikalai 2019-09-18 16:56
                  • Hybrid B/C Helmut 2019-09-18 17:09
                • AUC passes with 0.05 and Cmax with 0.0294 Elena777 2019-09-19 08:34
                  • Use data of all dosed subjects Helmut 2019-09-19 15:16
                    • Use data of all dosed subjects Elena777 2019-09-19 15:27
                      • ‘Method C’ ⇒ risky Helmut 2019-09-19 16:15
          • EEU-rules, TSD-methods (lengthy question) Elena777 2019-09-16 19:35
            • apple tree for two-stage Astea 2019-09-16 20:39
              • overripe apples Helmut 2019-09-16 23:37
                • override apples Astea 2019-09-17 06:14