View source: R/SampleSize_HVNTID.R
sampleN.HVNTID  R Documentation 
This function performs the sample size estimation for the BE decision via
the FDA’s method for highly variable NTIDs as described in respective guidances based on simulations.
The study designs may be the full replicate design 2x2x4 with 4 periods (TRTRRTRT) and
the 3period replicate design 2x2x3 with sequences RTRTRT.
sampleN.HVNTID(alpha = 0.05, targetpower = 0.8, theta0, theta1, theta2, CV, design = c("2x2x4", "2x2x3"), nsims = 1e+05, nstart, imax = 100, print = TRUE, details = TRUE, setseed = TRUE)
alpha 
Type I error probability. Per convention mostly set to 0.05. 
targetpower 
Power to achieve at least. Must be >0 and <1. 
theta0 
‘True’ or assumed T/R ratio. 
theta1 
Conventional lower ABE limit to be applied in the FDA procedure. 
theta2 
Conventional upper ABE limit to be applied in the FDA procedure. 
CV 
Intrasubject coefficient(s) of variation as ratio (not percent).

design 
Design of the study to be planned. 
nsims 
Number of simulations to be performed to obtain the empirical power. Defaults to 100,000 = 1e+5. 
nstart 
Set this to a start value for the sample size if a previous run failed. 
imax 
Maximum number of steps in sample size search. Defaults to 100. 
print 
If 
details 
If set to 
setseed 
Simulations are dependent on the starting point of the (pseudo) random number
generator. To avoid differences in power values for different runs a

For deciding BE the study must pass the conventional ABE test and additionally
the test that the ratio of sWT/sWR is <= 2.5.
The simulations are done via the distributional properties of the statistical
quantities necessary for deciding BE based on these method.
Details can be found in a document Implementation_scaledABE_sims
located in
the /doc
subdirectory of the package.
The estimated sample size gives always the total number of subjects (not subject/sequence – like in some other software packages).
Returns a data.frame with the input and sample size results.
The Sample size
column contains the total sample size.
The nlast
column contains the last n
value. May be useful for restarting.
For some input constellations the sample size search may be very time
consuming and will eventually also fail since the start values chosen may
not really reasonable for them.
In case of a failed sample size search you may restart with setting the argument
nstart
.
The design recommended by the FDA is the full replicate design "2x2x4"
.
The sample size estimation is done only for balanced studies since the
break down of the total subject number in case of unbalanced sequence groups
is not unique. Moreover the formulas used are only valid for balanced designs.
The FDA method is described for the ABE limits 0.8 ... 1.25 only. Setting theta1, theta2
to other values may not be reasonable and is not tested.
The minimum sample size is 6, even if the power is higher than the intended targetpower.
The method is also required by China’s Center of Drug Evaluation.
D. Labes
Food and Drug Administration, Office of Generic Drugs (OGD). Draft Guidance on Dabigatran Etexilate Mesylate. Recommended Jun 2012; Revised Sep 2015, Jul 2017. download
Food and Drug Administration, Office of Generic Drugs (OGD). Draft Guidance on Rivaroxaban. Recommended Sep 2015. download
Food and Drug Administration, Office of Generic Drugs (OGD). Draft Guidance on Edoxaban Tosylate. Recommended May 2017; Revised Mar 2020. download
power.HVNTID
and power.NTIDFDA
, sampleN.NTIDFDA
for NTIDs with
low variability
# using all defaults but CV sampleN.HVNTID(CV = 0.3) # should give # n=22 with an (empirical) power of 0.829700 # Test formulation with lower variability but same pooled CV CVs < CVp2CV(0.3, ratio = 0.25) sampleN.HVNTID(CV = CVs) # should give (no distinct difference to example above) # n=22 with an (empirical) power of 0.837520
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