deltaInverse {cir}

Calculate inverse (dose-finding) intervals, using local inversion and the Delta method

Description

Calculate left-bound to right-bound intervals for the dose point estimates, using local slopes at design points (places where observations exist) to invert the forward lower-upper bounds.

Usage

deltaInverse(
  isotPoint,
  target = (1:3)/4,
  intfun = morrisCI,
  conf = 0.9,
  adaptiveCurve = FALSE,
  minslope = 0.01,
  slopeRefinement = TRUE,
  finegrid = 0.05,
  ...
)

Arguments

isotPoint

The output of an estimation function such as cirPAVA,doseFind, with the option full=TRUE. Should be at least a list of 3 doseResponse objects named input, output, shrinkage.

target

A vector of target response rate(s), for which the interval is needed. Default (since version 2.3.0) is the 3 quartiles ((1:3) / 4). If changed to NULL, interval will be returned for the y values of isotPoint$output.

intfun

the function to be used for initial (forward) interval estimation. Default morrisCI (see help on that function for additional options).

conf

numeric, the interval's confidence level as a fraction in (0,1). Default 0.9.

adaptiveCurve

logical, should the CIs be expanded by using a parabolic curve between estimation points rather than straight interpolation (default FALSE)? Recommended when adaptive design was used and target is not 0.5.

minslope

minimum local slope (subsequently normalized by the units dose spacing) considered positive, passed on to slope. Needed to avoid unrealistically broad intervals. Default 0.01.

slopeRefinement

(new to 2.3.0) logical: whether to allow refinement of the slope estimate, including different slopes to the left and right of target. Default TRUE. See Details.

finegrid

a numerical value used to guide how fine the grid of x values will be during slope estimation. Should be in (0,1) (preferably much less than 1). Default 0.05.

...

additional arguments passed on to quickIsotone

Details

The Delta method in this application boils down to dividing the distance to the forward (vertical) bounds, by the slope, to get the left/right interval width. Both forward intervals and slopes are calculated across a standard set of x values, then interpolated at horizontal cross-sections determined by target. Slope estimates are performed by slope.

Starting version 2.3.0, by default the slope estimate is different to the right and left of target. The intervals should now better accommodate the sharp slope changes that often happen with discrete dose-response datasets. Operationally, the intervals are first estimated via the single-slope approach described above. Then using a finer grid of x values, weighted-average slopes to the right and left of the point estimate separately are calculated over the first-stage's half-intervals. The weights are hard-coded as quadratic (Epanechnikov).

An alternative and much simpler interval method (dubbed "global") is hard-coded into quickInverse, and can be chosen from there as an option. But it is not recommended.

Value

two-column matrix with the left and right bounds, respectively

See Also

quickIsotone,quickInverse,isotInterval, slope; DRshrink for the shrinkage fix.

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))
# The experiment's goal is to find the 30th percentile
quick1=quickIsotone(dat, adaptiveShrink = TRUE, target = 0.3)

# For inverse confidence intervals "the long way", 
#    we need a full CIR output object:
fwd1=cirPAVA(dat, full=TRUE, adaptiveShrink = TRUE, target = 0.3)
# Inverse intervals. 
# Note: 'target' specifies the y values at which the interval is calculated.
#       They are selected here based on the y range in which there are estimates.
yvals = c(seq(0.15, 0.3, 0.05), 0.33)
invDelta=deltaInverse(fwd1, target = yvals, adaptiveCurve = TRUE)
# We added the adaptiveCurve option because the experiment's target is off-center,
#     and inverse-interval coverage tends to be lacking w/o that option.

### Showing the data and the estimates
par(mar=c(3,3,4,1), mgp=c(2,.5,0), tcl=-0.25)
# Following command uses plot.doseResponse()
plot(dat, ylim=c(0.05,0.55), 
     las=1, xlim=c(0,6.5), main="Inverse-Estimation CIs") 

# The true response function; true target is where it crosses the y=0.3 line
lines(seq(0,7,0.1), pweibull(seq(0,7,0.1), shape=1.1615, scale=8.4839), col=4, lwd=1.5)
abline(h=0.3, col=2, lwd=2, lty=3) ### The experiment's official target

# Forward CIs; the "global" inverse interval just draws horizontal lines between them
# To get these "global" intervals calculated for you at specific targets, choose 'delta=FALSE' 
#      when calling quickInverse()
lines(quick1$y, lwd=1.5, col='purple') 
lines(quick1$lower90conf,lty=2,col=3) 
lines(quick1$upper90conf,lty=2,col=3) 
# Note that only the upper forward bounds intersect the horizontal line at y=0.3.
#   Therefore, via the "global" approach there won't be a finite CI for the target estimate.

# Now, the default "local" inverse interval, which is finite for the range of estimated y values.
# In particular, it is finite (albeit very wide) for y=0.3.
lines(invDelta[,1], yvals, lty=2, lwd=2)
lines(invDelta[,2], yvals, lty=2, lwd=2)

legend('topleft', pch=c(NA,NA,'X',NA,NA), lty=c(1,1,NA,2,2), 
       col=c(4,'purple', 1,1,3), lwd=c(1.5,1.5,0,2,1),
       legend = c('True Curve', 'CIR Curve', 'Observations', 
                  'Local Interval (default)',
                  'Forward/Global Interval'), bty='n')