PowerTOST (version 1.3-5)

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

Description

This function performs the power calculation of the BE decision via the FDA method for narrow therapeutic index drugs (NTID's) by simulations. The study design could be the full replicate design 2x2x4 with 4-periods or the 2x2x3 replicate design with sequences TRT|RTR.

Usage

power.NTIDFDA(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. Attention! Defaults here to 0.975 if not given explicitly. The value was chosen nearer to 1 because the potency (contents) settings for NTID's are tightened by the FDA.

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-sABEc) is the probability that the 95% CI of the ABE criterion is

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-sABEc) is the power of the BE test via scaled ABE criterion alone, p(BE-ABE) is the power of the conventional ABE test alone and p(BE-sratio) is the power of the criterion 'ratio of sWT/sWR is <= 2.5'="" alone.<="" li="">

Details

The linearized scaled ABE criterion is calculated according to the SAS code given in the FDA Warfarin guidance. For deciding BE the study must pass that criterion, the conventional ABE test and additional the test that the ratio of sWT/sWR is

References

FDA "Draft Guidance on Warfarin Sodium" Recommended Dec 2012 http://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/UCM201283.pdf LX Yu et al. "Novel bioequivalence approach for narrow therapeutic index drugs" Clin Pharm & Ther Vol 97, Issue 3, pages 286-291, March 2015 Article first published online: 15 DEC 2014 W Jiang et al. "A Bioequivalence Approach for Generic Narrow Therapeutic Index Drugs: Evaluation of the Reference-Scaled Approach and Variability Comparison Criterion" The AAPS Journal, July 2015, Volume 17, Issue 4, pp 891-901 First online: 04 April 2015 Laszlo Endrenyi and Laszlo Tothfalusi "Determination of Bioequivalence for Drugs with Narrow Therapeutic Index: Reduction of the Regulatory Burden" J Pharm Pharm Sci (www.cspsCanada.org) 16(5):676-682, 2013

See Also

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

Examples

# using the all defaults:
# GMR=0.975, theta1=0.8, theta2=1.25, 100 000 sims
# and a CV of 0.1 (= 10\%) with 12 subjects, balanced
power.NTIDFDA(CV=0.1, n=12)
# should give a power of 0.62553