PowerTOST (version 1.4-7)

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

Description

These functions performs the Sample size estimation via power calculations of 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", "2x2x3"), regulator, nsims = 1e+05, 
               nstart, imax=100, 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 <1. Typical values are 0.8 or 0.9.

theta0

'True' or assumed bioequivalence ratio. Defaults to 0.90 according to the "Two Laszlos" if not given explicitly.

theta1

Conventional lower ABE limit to be applied in the mixed procedure if CVsWR <= CVswitch. Also Lower limit for the point estimate constraint. Defaults to 0.8 if not given explicitly.

theta2

Conventional upper ABE limit to be applied in the mixed procedure if CVsWR <= CVswitch. Also upper limit for the point estimate 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). 2x2x3 is the 3-period replicate design (TRT|RTR). 2x2x4 is the full replicate design with 2 sequences and 4 periods. Defaults to design="2x3x3"

regulator

Regulatory settings for the widening of the BE acceptance limits. May be given as character from the choices "EMA", "HC", "FDA" or as an object of class 'regSet' (see reg_const). Defaults to regulator="EMA" if missing. This argument may be given also in lower case if given as character. The former regulator="ANVISA" is no longer allowed. Use "EMA" since ANVISA now recommends the use of EMA regulatory settings.

nsims

Number of simulations to be performed to obtain the (empirical) power. The default value 100 000 = 1e+5 is usually sufficient. Consider to rise this value if theta0<=0.85 or >=1.25. But see the warning section.

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.

imax

Maximum number of steps in sample size search. Defaults to 100.

print

If TRUE (default) the function prints its results.

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 a data.frame with the input settings 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 very extreme theta0 (<0.83 or >1.21) 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 in the range around CV = 0.3 and regulatory constant according to FDA. If you really need sample sizes in that range be prepared to restart the sample size estimation via the argument nstart. Since the dependence of power from n is very flat in the mentioned region you may also consider to adapt the number of simulations not to tap in the simulation error trap. See also the Warning section of the function power.scABEL() concerning the power value agreement to those obtained from simulations via subject data. sampleN.scABEL2() is deprecated and will be removed in future. A corresponding warning is thrown if this function is used.

Details

The simulations are done via the distributional properties of the statistical quantities necessary for deciding BE based on widened ABEL. For more details see a description in the doc subdirectory of the package. Function sampleN.scABEL() is based on power calculations via simulations using the distributional characteristics of the 'key' statistics obtained from the EMA recommended evaluation via ANOVA if regulator="EMA" or if the regulator component est_method is set to "ANOVA" if regulator is an object of class 'regSet'. Otherwise the simulations are based on the distributional characteristis of the 'key' statistics obtained from evaluation via intra-subject contrasts (ISC), as recommended by the FDA. Function sampleN.scABEL2() is soleyly based on power calculations via simulation using the distributional characteristics of the 'key' statistics obtained from evaluation via ISC. This function is deprecated.

References

T<U+00F3>thfalusi L, Endr<U+00E9>nyi L. Sample Sizes for Designing Bioequivalence Studies for Highly Variable Drugs J Pharm Pharmaceut Sci. 2011;15(1):73--84. free download

See Also

power.scABEL, power.RSABE, sampleN.RSABE, reg_const

Examples

# NOT RUN {
# using all the defaults:
# partial replicate design, targetpower=80%,
# true assumed ratio = 0.90, 1E+5 simulated studies
# ABE limits, PE constraint 0.8 - 1.25
# EMA regulatory settings
sampleN.scABEL(CV=0.3)
# should result in a sample size n=54, power=0.8159
#
# now with former (inofficial) ANVISA settings, CVswitch=40%
# (now ANVISA uses the same settings as EMA)
reg <- reg_const("USER", r_const=0.76, CVswitch=0.4, CVcap=0.5)
reg$name <- "Old ANVISA"
sampleN.scABEL(CV=0.3, regulator=reg)
# should result in n=60, power=0.8101

# for the full replicate design, target power = 90%
# true assumed ratio = 0.9, FDA regulatory settings
# sims based on evalaution via ISC
sampleN.scABEL(CV=0.4, targetpower=0.9, theta0=0.9, design="2x2x4", regulator="FDA")
# should result in a sample size n=32, power=0.9125
# }