PowerTOST (version 1.1-00)

sampleN.scABEL: Sample size estimation for BE via scaled (widened) BE acceptance limits

Description

This function performs the Sample size estimation for the BE decision via scaled (widened) BE acceptance limits based on simulations.

Usage

sampleN.scABEL(alpha = 0.05, targetpower = 0.8, theta0, theta1, theta2, 
               CV, design = c("2x3x3", "2x2x4"), regulator = c("EMA", "FDA"), 
               nsims = 1e+06, nstart, print = TRUE, details = TRUE)

Arguments

alpha

Type I error probability. Per convention mostly set to 0.05.

targetpower

Power to achieve at least. Must be >0 and

theta0

'True' or assumed bioequivalence ratio. Defaults to 0.95 if given explicitly.

theta1

Lower limit for the point estimator constraint. Defaults to 0.8 if not given explicitly.

theta2

Upper limit for the point estimator constraint. Defaults to 1.25 if not given explicitly.

CV

Coefficient(s) of variation as ratio. If length(CV) = 1 the same CV is assumed for Test and Reference. If length(CV) = 2 the CV for Test must be given in CV[1] and for Reference in CV[2].

design

Design of the study to be planned. 2x3x3 is the partial replicate design (TRR/RTR/RRT). 2x2x4 is the full replicate design with 2 sequences and 4 periods. Defaults to design="2x3x3"

regulator

Regulatory body settings for the widening of the BE acceptance limits. Defaults to design="EMA"

nsims

Number of simulations to be performed to obtain the (empirical) power.

nstart

Set this to a start for the sample size if a previous run failed.

print

If TRUE (default) the function prints its results. If FALSE only the sample size will be returned.

details

If set to TRUE, the default, the steps during sample size search are shown.

Value

• Returns the numerical value of the sample size.

Warning

The sample size estimation for theta0 >= 1.2 and <=0.83 may="" be="" very="" time="" consuming="" and="" will="" eventually="" also="" fail="" since="" the="" start="" values="" chosen="" are="" not="" really="" reasonable="" in="" that="" ranges.="" this="" is="" especially="" true="" if="" you="" choose="" a="" target="" power="">0.8 and your CV is >0.5. If you really need sample sizes in that range be prepared to restart the sample size estimation via the argument nstart.

Details

The simulations are done via the distributional properties of the statistical quantities necessary for deciding BE based on widened ABEL.

References

Laszlo Tothfalusi and Laszlo Endrenyi "Sample Sizes for Designing Bioequivalence Studies for Highly Variable Drugs" J. Pharm. Pharmaceut. Sci. (www.cspsCanada.org) 15(1) 73 - 84, 2011

See Also

power.scABEL

Examples

#using all the defaults
sampleN.scABEL(CV=0.3)
# results in a sample size n=27

# for the full replicate design, target power = 90%
# true assumed ratio = 0.9, FDA regulatory settings
sampleN.scABEL(CV=0.4, targetpower=0.9, theta0=0.9, design="2x2x4", regulator="FDA")
# results in a sample size n=32