PowerTOST (version 1.2-09)

sampleN.RSABE: Sample size estimation for BE decision via linearized scaled ABE criterion

Description

This function performs the Sample size estimation for the BE decision via linearized scaled ABE criterion based on simulations.

Usage

sampleN.RSABE(alpha = 0.05, targetpower = 0.8, theta0, theta1, theta2, CV,
              design = c("2x3x3", "2x2x4", "2x2x3"), regulator = c("FDA", "EMA"),
              nsims = 1e+05, nstart, print = TRUE, details = TRUE, setseed=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

Conventional lower ABE limit to be applied in the mixed procedure if CVsWR

theta2

Conventional upper ABE limit to be applied in the mixed procedure if CVsWR

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. 2x2x3 is the 3-period design with sequences (TRT|RTR). Defaults to design="2x3x3"

regulator

Regulatory body settings for the scaled ABE criterion. Defaults to design="FDA". Also the scaled ABE criterion is usually calculated with the FDA constant r_const=log(1.25)/0.25 you can override this behavior to use the EMA setting r_const=

nsims

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

nstart

Set this to a start for the sample size search if a previous run failed. After reworking the start n in version 1.1-05 seldom needed.

print

If TRUE (default) the function prints its results. If FALSE only the result data.frame will be returned.

details

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

setseed

Simulations are dependent on the starting point of the (pseudo) random number generator. To avoid differences in power for different runs a set.seed(123456) is issued if setseed=TRUE, the default.

Value

• Returns now 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.

Warning

The sample size estimation for theta0 >1.2 and

Details

The linearized scaled ABE criterion is calculated according to the SAS code given in the FDA progesterone guidance. The simulations are done via the distributional properties of the statistical quantities necessary for deciding BE based on scaled ABE. For more details see a document "Implementation_scaledABE_simsVx.yy.pdf" in the doc subdirectory of the package.

References

FDA "Draft Guidance on Progesterone" Recommended Apr 2010; Revised Feb 2011 http://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/ Guidances/UCM209294.pdf 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 Tothfalusi L., Endrenyi L. and A. Garcia Arieta "Evaluation of Bioequivalence for Highly Variable Drugs with Scaled Average Bioequivalence" Clin. Pharmacokin. 48/11, 725-743 (2009)

See Also

power.RSABE, power.scABEL

Examples

# using all the defaults:
# design=2x3x3 (partial replicate design), theta0=0.95, 
# ABE limits, PE constraint 0.8 - 1.25
# targetpower=80\%, alpha=0.05, 1E5 sims
sampleN.RSABE(CV=0.3)
# results in a sample size n=27, power=0.84132