PowerTOST (version 1.4-7)

scABEL: Scaled (widened) BE Acceptance Limits

Description

The (widened) scaled BE acceptance limits are calculated according to the regulatory settings of EMA, HC, FDA or via user defined regulatory settings.

Usage

scABEL(CV, regulator)

Arguments

CV

Coefficient of variation (of the Reference) as ratio.

regulator

Regulatory body 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. The former regulator="ANVISA" is no longer allowed. Use "EMA" since ANVISA now recommends the use of EMA regulatory settings. The former regulator="USER" is no longer accepted but can be handled now via function reg_const() to define an object with class 'regSet'.

Value

Returns a vector of lenghth 2 if one CV is given or a matrix if CV is given as vector with named components "lower" and "upper" of the scaled acceptance limits.

Details

The widened BE acceptance limits will be calculated by the formula [lBEL,uBEL] =exp(-+ r_const*sWR) with r_const the regulatory constant and sWR the standard deviation of the within subjects variability of the Reference. r_const=0.76 (~log(1.25)/0.29356) is used in case of regulator="EMA" or regulator="HC" and in case of regulator="FDA" r_const=0.89257...(=log(1.25)/0.25). If the CVwR of the Reference is < CVswitch=0.3 the conventional ABE limits apply (mixed procedure). In case of regulator="EMA" a cap is placed on the widened limits if CVwr>0.5, i.e. the widened limits are held at value calculated for CVwR=0.5. In case of regulator="HC" the capping is done such that the acceptance limits are 0.6666 ... 1.5 at maximum, i.e. CVcap=0.57382. Literally it was given rounded to 3 significant digits as 57.4%. See http://www.hc-sc.gc.ca/dhp-mps/prodpharma/activit/announce-annonce/notice-avis-be-hvdp-nb-pphv-eng.php

References

Davit et al. Implementation of a Reference-Scaled Average Bioequivalence Approach for Highly Variable Generic Drug Products by the US Food and Drug Administration AAPS J. 2012;14(4):915--24. 10.1208/s12248-012-9406-x

See Also

power.scABEL, sampleN.scABEL, reg_const

Examples

# NOT RUN {
scABEL(CV=0.3, regulator="EMA")
# should give the usual BE limits:
# lower  upper
#  0.80   1.25
scABEL(CV=0.4, regulator="EMA")
# should give the widened limits:
#   lower     upper
# 0.746177 1.340165
#
# define old ANVISA settings via reg_const()
rc <- reg_const("USER", r_const=0.76, CVswitch=0.4, CVcap=0.5)
rc$name <- "ANVISAold"
scABEL(CV=0.4, regulator=rc)
# should give the not widened limits:
# lower upper 
#  0.80  1.25 
# }