estimateIAE: BRAID Response Surface Combined Potency

In braidrm: Fitting Combined Action with the BRAID Response Surface Model

BRAID Response Surface Combined Potency

Description

Estimates the BRAID index of achievable efficacy (or IAE) for a given response surface

Usage

estimateIAE(bpar, levels, limits, lowerLimits = c(0, 0))

## S3 method for class 'braidrm'
estimateIAE(bpar, levels, limits, lowerLimits = c(0, 0))

## S3 method for class 'braidrmflip'
estimateIAE(bpar, levels, limits, lowerLimits = c(0, 0))

## Default S3 method:
estimateIAE(bpar, levels, limits, lowerLimits = c(0, 0))

estimateFlippedIAE(bpar, flip, levels, limits, lowerLimits = c(0, 0))

Arguments

bpar	The response surface to be evaluated. Can be a numeric vector (which will be treated as a standard BRAID parameter vector), a BRAID fit object of class braidrm, or a flipped BRAID fit object of class braidrmflip
levels	The effect level or levels at which the index is to be estimated
limits	The upper concentration limits beneath which the IAE is to be estimated. Could be known toxicity thresholds, limits on pharmacokinetic availability, or simply a convenient and consistent reference concentration
lowerLimits	By default, the IAE is calculated by comparing the area of dose space below which a given effect level is not reached with the total achievable dose space specified by limits. However, in some cases, it is not desirable to allow the sub-threshold area to become infinitesimally small. If lowerLimits is included, doses that lie below both lower limits will always be included in the sub-threshold area, placing an effective upper bound on possible IAE values
flip	String specifying the direction or directions of the surface's flip. Must be one of "A", "B", or "both".

Details

The index of achievable efficacy is an aggregate measure of combined potency, and a useful first pass for quantifying the efficacy of a given response surface. Formally, it is equal to the area of achievable dose pairs divided by the area of achievable doses below which a desired effect level is not reached (then passed through a square root to give a more dimensionless result). If the surface is more potent, the area of sub-threshold achievable doses is smaller, and the IAE is larger. If the surface is less efficacious, the doses at which a desired effect is reach will be larger, the sub-threshold area will increase, and the IAE will decrease. By default, the IAE can range from 1 to infinity, but upper bounds can be placed by setting the values in lowerLimits to concentrations above 0. For convenience, the function takes BRAID parameter vectors, braidrm fit objects, and braidrmflip flipped BRAID fit objects. However, flipped BRAID response surface parameters cannot be passed to the function as is, so the function estimateFlippedIAE is also included specifically for flipped parameter vectors.

Value

A numeric vector, the same length as levels with the estimated index of achievable efficacy (IAE) values for each of those levels.

Examples

estimateIAE(c(1,1,3,3,0,0,100),c(50,90),c(5,5))

bfit <- braidrm(measure ~ concA + concB, synergisticExample, getCIs = FALSE)
estimateIAE(bfit, c(0,0.25,0.5,0.75,1), c(10,1), lowerLimits=c(0.01,0.01))

braidrm documentation built on Sept. 30, 2024, 9:40 a.m.