PowerTOST (version 1.3-5)

sampleN.HVNTID: Sample size estimation for BE decision via FDA method for highly variable (HV) narrow therapeutic index drugs (NTID's)

Description

This function performs the Sample size estimation for the BE decision via FDA method for highly variable NTID's as described in the FDA Dabigatran / Rivaroxaban guidances based on simulations. The study designs may be the full replicate design 2x2x4 with 4 periods and the 3-period replicate design 2x2x3 with sequences RTR|TRT.

Usage

sampleN.HVNTID(alpha = 0.05, targetpower = 0.8, theta0, theta1, theta2, CV, 
               design=c("2x2x4", "2x2x3"), 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

theta0

'True' or assumed bioequivalence ratio. Defaults to 0.95 if not given explicitly.

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.

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. 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.

nstart

Set this to a start value for the sample size if a previous run failed. May be missing.

imax

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

print

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

details

If set to TRUE, the default, the steps during sample size search are shown. Moreover the details of the method settings are printed.

setseed

Simulations are dependent on the starting point of the (pseudo) random number generator. To avoid differences in power values 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 re-starting.

Warning

For some input constellations the sample size search may be very time consuming and will eventually also fail since the start values chosen may not really reasonable for them. In case of a failed sample size search you may restart with setting the argument nstart.

Details

For deciding BE the study must pass the conventional ABE test and additionally the test that the ratio of sWT/sWR is

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

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

Examples

# using all defaults but CV
sampleN.HVNTID(CV=0.3)
# should give
# n=22 with an (empirical) power of 0.829700

# Test formulation with lower variability but same pooled CV
CVs <- CVp2CV(0.3, ratio=0.25)
sampleN.HVNTID(CV=CVs)
# should give (no distinct difference to example above)
# n=22 with an (empirical) power of 0.837520