PowerTOST (version 1.3-5)

power.HVNTID: (Empirical) Power for BE decision via FDA method for highly variable NTID's

Description

This function performs the power calculation of the BE decision via the FDA method for highly variable narrow therapeutic index drugs (NTID's) as described in the FDA Dabigatran / Rivaroxaban guidances based on simulations. The study design could be the full replicate design 2x2x4 with 4-periods or the 2x2x3 replicate design with 3-periods and sequences TRT|RTR.

Usage

power.HVNTID(alpha = 0.05, theta1, theta2, theta0, CV, n, design=c("2x2x4", "2x2x3"), 
             nsims = 1e+05, details = FALSE, setseed = TRUE)

Arguments

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. Defaults to 0.8 if not given explicitly.

theta2

Conventional upper ABE limit to be applied in the FDA procedure. Defaults to 1.25 if not given explicitly.

theta0

'True' or assumed bioequivalence ratio. Defaults to 0.95 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].

n

Number of subjects under study. May be given as vector. In that case it is assumed that n contains the number of subjects per sequence groups. Attention! In case of the 2x2x3 (TRT|RTR) design the order of n's important if given as vector. n[1] is for s

design

Design of the study to be planned. 2x2x4 is the full replicate design with 2 sequences and 4 periods. 2x2x3 is the 3-period replicate design with sequences TRT|RTR. Defaults to design="2x2x4".

nsims

Number of simulations to be performed to obtain the empirical power. Defaults to 100 000 = 1e+5.

details

If set to TRUE the computational time is shown as well as the components for the BE decision. p(BE-ABE) is the simulated probability for the conventional ABE test. p(BE-sratio) is the probability that the upper 90% confidence limit of the

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 the value of the (empirical) power if argument details=FALSE. Returns a named vector if argument details=TRUE. p(BE) is the power, p(BE-ABE) is the power of the ABE test alone and p(BE-sratio) is the power of the criterion 'ratio of sWT/sWR is <= 2.5'="" alone.<="" li="">

Details

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.

References

FDA "Draft Guidance on Dabigatran Etexilate Mesylate" Recommended Jun 2012; Revised Sept 2015 http://www.fda.gov/downloads/drugs/guidancecomplianceregulatoryinformation/guidances/ucm308030.pdf FDA "Draft Guidance on Rivaroxaban" Recommended Sept 2015 http://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/UCM461150.pdf

See Also

sampleN.HVNTID and power.NTIDFDA, sampleN.NTIDFDA for NTIDs with low variability

Examples

# using the defaults:
# GMR=0.95, theta1=0.8, theta2=1.25, full replicate design 2x2x4, 100 000 sims
# 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