ANVISA: TIE, sample size [RSABE / ABEL]
Hi ElMaestro,
No? IMHO, it is not more unjustified than EMA’s. The EMA had no negative results from arbitrarily widening the AR to 0.70~1.43 (pre-2006, 2×2 crossover sufficient; widening also for AUC!) or to 0.75~1.33 (2006+, replicate design, Cmax only). There are hundreds (?) of products authorized according to those requirements. This “evidence” explains EMA’s cap on the CVWR of 50%. They didn’t want to reach beyond what they have accepted before.
On the contrary FDA’s scaling came out of the blue… For CVs > ~50% the restriction on the PE of 0.80~1.25 is more important than the CI. Since in Canada (1991+) only the PE of Cmax has to lie with 0.80~1.25 there is some evidence across the pond that it “works” as well. Experience with AUC? Nada.
Reading ANVISA’s response over and over again, I gather that they mean #1 in order to be on the safe side (“EMA accepts reference-scaling for five years now. Let’s be slightly more conservative.”). At least some of the inflation of the Type I Error observed with EMA’s “method” vanishes (I expect still a TIE of ~0.06 at 40%). Until Detlew releases an (experimental?) update for
❝ […] But then realised that of course no agency will be enforcing such a weird and unjustified requirement.
No? IMHO, it is not more unjustified than EMA’s. The EMA had no negative results from arbitrarily widening the AR to 0.70~1.43 (pre-2006, 2×2 crossover sufficient; widening also for AUC!) or to 0.75~1.33 (2006+, replicate design, Cmax only). There are hundreds (?) of products authorized according to those requirements. This “evidence” explains EMA’s cap on the CVWR of 50%. They didn’t want to reach beyond what they have accepted before.
On the contrary FDA’s scaling came out of the blue… For CVs > ~50% the restriction on the PE of 0.80~1.25 is more important than the CI. Since in Canada (1991+) only the PE of Cmax has to lie with 0.80~1.25 there is some evidence across the pond that it “works” as well. Experience with AUC? Nada.
Reading ANVISA’s response over and over again, I gather that they mean #1 in order to be on the safe side (“EMA accepts reference-scaling for five years now. Let’s be slightly more conservative.”). At least some of the inflation of the Type I Error observed with EMA’s “method” vanishes (I expect still a TIE of ~0.06 at 40%). Until Detlew releases an (experimental?) update for
PowerTOST
’s *.scABEL
functions (regulator="ANVISA"
) one can only assume the worst in sample size estimation, i.e., unscaled ABE, theta0=0.9
, CV=0.4
…—
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
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:
- ANVISA’s home brewed scaling? Helmut 2015-05-28 18:27 [RSABE / ABEL]
- ANVISA’s home brewed scaling? ElMaestro 2015-05-28 19:10
- ANVISA: TIE, sample sizeHelmut 2015-06-02 16:00
- ANVISA: scABEL TIE d_labes 2015-06-03 11:59
- ANVISA: scABEL TIE Helmut 2015-06-03 12:07
- ANVISA: scABEL TIE part II d_labes 2015-06-03 13:19
- ANVISA: scABEL TIE part II nobody 2015-06-03 13:31
- ANVISA: scABEL TIE part II d_labes 2015-06-03 14:00
- ANVISA: scABEL TIE part II nobody 2015-06-03 13:31
- ANVISA scABEL - sample size d_labes 2015-06-05 11:03
- ANVISA: scABEL TIE part II d_labes 2015-06-03 13:19
- ANVISA: scABEL TIE Helmut 2015-06-03 12:07
- ANVISA: scABEL TIE d_labes 2015-06-03 11:59
- ANVISA: TIE, sample sizeHelmut 2015-06-02 16:00
- ANVISA’s home brewed scaling? Lucas 2015-06-02 16:02
- ANVISA’s home brewed scaling? Helmut 2015-06-02 16:16
- ANVISA’s home brewed scaling? ElMaestro 2015-05-28 19:10