power.HVNTID  R Documentation 
This function performs the power calculation of the BE decision via the FDA’s method for highly variable narrow therapeutic index drugs (NTIDs) as described in respective guidances based on simulations. The study design could be the full replicate design 2x2x4 with 4periods (TRTRRTRT) or the 2x2x3 replicate design with 3periods and sequences TRTRTR.
power.HVNTID(alpha = 0.05, theta1, theta2, theta0, CV, n, design = c("2x2x4", "2x2x3"), nsims = 1e+05, details = FALSE, setseed = TRUE)
alpha 
Type I error probability, significance level. Commonly set to 0.05. 
theta1 
Conventional lower ABE limit to be applied in the FDA procedure. 
theta2 
Conventional upper ABE limit to be applied in the FDA procedure. 
theta0 
‘True’ or assumed T/R ratio. 
CV 
Intrasubject coefficient(s) of variation as ratio (not percent).

n 
Number of subjects under study. 
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. 
details 
If set to 
setseed 
Simulations are dependent on the starting point of the (pseudo) random number
generator. To avoid differences in power for different runs a 
For deciding BE the study must pass the conventional ABE test (90% CI within the
acceptance range) and additional 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 this method.
Details can be found in a document Implementation_scaledABE_sims
located in
the /doc
subdirectory of the package.
Returns the value of the (empirical) power if argument details=FALSE
.
Returns a named vector if argument details=TRUE
.
p(BE) is the power, p(BEABE) is the power of the ABE test alone and p(BEsratio)
is the power of the criterion 'ratio of sWT/sWR is <= 2.5' alone.
The FD’s guidances recommend only the full replicate design "2x2x4" (TRTRRTRT).
The results for the design "2x2x3" (TRTRTR) are to be considered as experimental since
at present not thorougly tested.
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 Draft Guidance on Dabigatran Etexilate Mesylate.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 Draft Guidance on Rivaroxaban.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
sampleN.HVNTID
and power.NTIDFDA
, sampleN.NTIDFDA
for NTIDs with
low variability
# using the defaults: # GMR=0.95, theta1=0.8, theta2=1.25, full replicate design 2x2x4, 100,000 simulations # and a CV of 0.3 (=30%) for both Reference and Test, with 24 subjects, balanced power.HVNTID(CV = 0.3, n = 24) # should give a power of 0.86354
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