Sample sizes are not prohibitive [Regulatives / Guidelines]
❝ […] Maybe it's tooooo new after all.
Maybe. Sample sizes are not that bad. The FDA requires tighter release spec’s. Hence, we implemented 0.975 as the default in
PowerTOST
.library(PowerTOST)
CVwR <- 0.1 # e.g., Cmax of valproic acid (AUC has ~0.05).
s.r <- 1 # ratio of swT/swR
CVwT <- mse2CV(CV2mse(CVwR)*s.r)
sampleN.NTIDFDA(CV=c(CVwT, CVwR), details=FALSE)
+++++++++++ FDA method for NTID's +++++++++++
Sample size estimation
---------------------------------------------
Study design: 2x2x4
log-transformed data (multiplicative model)
1e+05 studies for each step simulated.
alpha = 0.05, target power = 0.8
CVw(T) = 0.1, CVw(R) = 0.1
True ratio = 0.975
ABE limits = 0.8 ... 1.25
Regulatory settings: FDA
Sample size
n power
18 0.841790
Now swT∕swR 2.
s.r <- 2
CVwT <- mse2CV(CV2mse(CVwR)*s.r)
sampleN.NTIDFDA(CV=c(CVwT, CVwR), details=FALSE)
+++++++++++ FDA method for NTID's +++++++++++
Sample size estimation
---------------------------------------------
Study design: 2x2x4
log-transformed data (multiplicative model)
1e+05 studies for each step simulated.
alpha = 0.05, target power = 0.8
CVw(T) = 0.1417745, CVw(R) = 0.1
True ratio = 0.975
ABE limits = 0.8 ... 1.25
Regulatory settings: FDA
Sample size
n power
28 0.817760
Boehringer’s formulation change. The family’s slaves planned for T/R 0.85 (tried at lot, couldn’t do better), a CVwR of 80%, and RSABE (old guidance). That’s the infamous 4-period full replicate study in 180 subjects on ClinicalTrials.gov.
Nowadays:
sampleN.NTIDFDA(CV=0.8, theta0=0.85, details=FALSE)
+++++++++++ FDA method for NTID's +++++++++++
Sample size estimation
---------------------------------------------
Study design: 2x2x4
log-transformed data (multiplicative model)
1e+05 studies for each step simulated.
alpha = 0.05, target power = 0.8
CVw(T) = 0.8, CVw(R) = 0.8
True ratio = 0.85
ABE limits = 0.8 ... 1.25
Regulatory settings: FDA
Sample size
n power
836 0.800870
Dif-tor heh smusma 🖖🏼 Довге життя Україна!
Helmut Schütz
The quality of responses received is directly proportional to the quality of the question asked. 🚮
Science Quotes
Complete thread:
- FDA BE Guide Warfarin – never used? nobody 2017-07-13 15:13 [Regulatives / Guidelines]
- FDA BE Guide Warfarin – never used? Helmut 2017-07-13 16:53
- FDA BE Guide Warfarin – never used? nobody 2017-07-13 19:00
- Sample sizes are not prohibitiveHelmut 2017-07-13 19:54
- Sample sizes are not prohibitive nobody 2017-07-13 20:12
- Sample sizes are not prohibitive Helmut 2017-07-13 20:36
- Sample sizes are not prohibitive nobody 2017-07-13 20:12
- Sample sizes are not prohibitiveHelmut 2017-07-13 19:54
- FDA BE Guide Warfarin – never used? nobody 2017-07-13 19:00
- FDA BE Guide Warfarin – never used? Helmut 2017-07-13 16:53