View source: R/power_RSABE_NTID.R
power.NTID  R Documentation 
This function performs the power calculation of the BE decision via the FDA’s method for narrow therapeutic index drugs (NTIDs) by simulations. The study design could be the full replicate design 2x2x4 with 4periods (TRTRRTRT) or the 2x2x3 replicate design with sequences TRTRTR.
power.NTID(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. Conventionally mostly 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 
The linearized scaled ABE criterion is calculated according to the SAS code
given in the FDA’s guidances. For deciding BE the study must pass that criterion,
the conventional ABE test, and that the upper confidence limit of
σ_{wT}/σ_{wR} ≤ 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.
Returns the value of the (empirical) power if argument details = FALSE
.
Returns a named vector if argument details = TRUE
, where
p(BE)
is the (overall) power, p(BEsABEc)
is the power of the BE test via scaled ABE criterion alone,
p(BEABE)
is the power of the conventional ABE test alone, and p(BEsratio)
is the power of the criterion ‘upper confidence limit of
σ_{wT}/σ_{wR} ≤ 2.5’ alone.
The FDA’s 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 results for the design "2x2x3"
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 Draft Guidance on Warfarin Sodium. Recommended Dec 2012. download
Food and Drug Administration, Center for Drug Evaluation and Research (CDER). Draft Guidance for Industry. Bioequivalence Studies with Pharmacokinetic Endpoints for Drugs Submitted Under an ANDA. August 2021. download
Yu LX, Jiang W, Zhang X, Lionberger R, Makhlouf F, Schuirmann DJ, Muldowney L, Chen ML, Davit B, Conner D, Woodcock J. Novel bioequivalence approach for narrow therapeutic index drugs. Clin Pharmacol Ther. 2015;97(3):286–91. doi: 10.1002/cpt.28
Jiang W, Makhlouf F, Schuirmann DJ, Zhang X, Zheng N, Conner D, Yu LX, Lionberger R. A Bioequivalence Approach for Generic Narrow Therapeutic Index Drugs: Evaluation of the ReferenceScaled Approach and Variability Comparison Criterion. AAPS J. 2015;17(4):891–901. doi: 10.1208/s1224801597535
Endrényi L, Tóthfalusi L. Determination of Bioequivalence for Drugs with Narrow Therapeutic Index: Reduction of the Regulatory Burden. J Pharm Pharm Sci. 2013;16(5):676–82. open access
sampleN.NTID
and power.HVNTID
, sampleN.HVNTID
for NTIDs with
high variability
# using the all defaults: # GMR=0.975, theta1=0.8, theta2=1.25, 100,000 simulations # and a CV of 0.1 (= 10%) with 12 subjects, balanced power.NTID(CV = 0.1, n = 12) # should give a power of 0.62553
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