R: One-Stop-shop Forward point and interval estimation via CIR...

quickIsotone {cir}

R Documentation

One-Stop-shop Forward point and interval estimation via CIR or IR

Description

One-Stop-shop Forward point and confidence-interval estimation of a monotone response (y) as a function of dose (x), using centered-isotonic-regression (CIR, default) or isotonic regression. Input format is rather flexible. This function calls cirPAVA, oldPAVA, iterCIR (speculatively), or a user-written function, for the point estimate, then isotInterval for the confidence interval. Vector input is allowed, but the preferred input format is a doseResponse object. An analogous function for dose-finding (inverse estimation) is quickInverse.

Usage

quickIsotone(
  y,
  x = NULL,
  wt = NULL,
  outx = NULL,
  dec = FALSE,
  estfun = cirPAVA,
  intfun = morrisCI,
  conf = 0.9,
  adaptiveShrink = FALSE,
  ...
)

Arguments

`y`	can be either of the following: y values (response rates), a 2-column matrix with positive/negative response counts by dose, a `DRtrace` object or a `doseResponse` object.
`x`	dose levels (if not included in y). Note that the PAV algorithm doesn't really use them.
`wt`	weights (if not included in y).
`outx`	vector of x values for which predictions will be made. If `NULL` (default), this will be set to the set of unique values in the `x` argument (or equivalently in `y$x`).
`dec`	logical, is the true function assumed to be monotone decreasing rather than increasing? Default `FALSE`.
`estfun`	the function to be used for point estimation. Default `cirPAVA`.
`intfun`	the function to be used for interval estimation. Default `wilsonCI` (see help on that function for additional options).
`conf`	numeric, the interval's confidence level as a fraction in (0,1). Default 0.9.
`adaptiveShrink`	logical, should the y-values be pre-shrunk towards an experiment's target? Recommended if data were obtained via an adaptive dose-finding design. If `TRUE`, then must also provide a `target` argument that will be passed via `...`.
`...`	arguments passed on to other functions (constructor, point estimate and interval estimate).

Value

A data frame with 4 variables:

x either the input x values, or outx of specified;
y The point estimates of x
lowerPPconf,upperPPconf the interval-boundary estimates for a 'PP'=100*conf confidence interval

Note

You can obtain interpolated point estimates for x values between the observed data by specifying them via outx. However, for CIR, do NOT commit the error of generating estimates at observations, then interpolating using approx. If you need to retain a set of estimates for plotting the entire fitted curve, or for future interpolation at unknown points, call cirPAVA directly with full=TRUE, then use the returned shrinkage data frame for plotting and interpolation. See example code below.

If the data were obtained from an adaptive dose-finding design then away from the design's target the estimates are likely biased (Flournoy and Oron, 2020). Use adaptiveShrink=TRUE to mitigate the bias.

Author(s)

Assaf P. Oron <assaf.oron.at.gmail.com>

References

Oron, A.P. and Flournoy, N., 2017. Centered Isotonic Regression: Point and Interval Estimation for Dose-Response Studies. Statistics in Biopharmaceutical Research 9, 258-267. (author's public version available on arxiv.org).

Flournoy, N. and Oron, A.P., 2020. Bias Induced by Adaptive Dose-Finding Designs. Journal of Applied Statistics 47, 2431-2442.

Examples

# Interesting run (#664) from a simulated up-and-down ensemble:
# (x will be auto-generated as dose levels 1:5)
dat=doseResponse(y=c(1/7,1/8,1/2,1/4,4/17),wt=c(7,24,20,12,17))
# CIR, using the default 'quick' function that also provides CIs (default 90%).
# The experiment's goal is to find the 30th percentile. We deploy the empirical bias correction.
quick1=quickIsotone(dat, adaptiveShrink = TRUE, adaptiveCurve = TRUE, target = 0.3)
quick1
# Use 'estfun' argument to operate the same function with old PAVA as the estimator
# Here we neglect the bias correction to sharpen the old:new contrast
quick0=quickIsotone(dat,estfun=oldPAVA)
quick0

### Showing the data and the fits
par(mar=c(3,3,1,1),mgp=c(2,.5,0),tcl=-0.25)
plot(dat, ylim=c(0.05,0.55), las=1) # uses plot.doseResponse()
# The IR fit: a straightforward interpolation
lines(quick0$y,lty=2) 

# With CIR, 'quickIsotone' cannot show us the true underlying interpolation; 
# it only provides the estimates at requested points.  Interpolation should be done between 
# shrinkage points, not the original design points. So we must call the full 'cirPAVA' function:

slow1 = cirPAVA(dat, full=TRUE, adaptiveShrink = TRUE, adaptiveCurve = TRUE, target = 0.3)
# Now, compare these 3 (the first one is wrong, b/c it interpolates from design points):
midpts = 1:4 + 0.5
approx(1:5,quick1$y, xout=midpts)$y
# instead, you can just call 'quickIsotone' and specify 'outx'
quickIsotone(dat,outx=midpts , adaptiveShrink = TRUE, adaptiveCurve = TRUE, target = 0.3) 
approx(slow1$shrinkage$x,slow1$shrinkage$y,xout=midpts)$y # Or use 'cirPAVA'

# Ok... finally plotting the CIR curve
# Both flat intervals are shrunk, because neither are at y=0 or y=1
lines(slow1$shrinkage$x,slow1$shrinkage$y, lwd = 2)

# Last but not least, here's the true response function
lines(seq(1,5,0.1),pweibull(seq(1,5,0.1),shape=1.1615,scale=8.4839),col=2)
legend('topleft',pch=c(NA,'X',NA,NA),lty=c(1,NA,2,1),col=c(2,1,1,1),
	legend=c('True Curve','Observations','IR','CIR'), bty='n')

[Package cir version 2.3.1 Index]