Re: [R] drc results differ for different versions

Wed, 20 May 2009 11:27:50 -0700 

On May 20, 2009, at 11:20 AM, Hans Vermeiren wrote:


Hello,

We use drc to fit dose-response curves, recently we discovered that
there are quite different standard error values returned for the same
dataset depending on the drc-version / R-version that was used (not
clear which factor is important)
On R 2.9.0 using drc_1.6-3 we get an IC50 of 1.27447 and a standard
error on the IC50 of 0.43540
Whereas on R 2.7.0 using drc_1.4-2  the IC50 is 1.2039e+00 and the
standard error is 3.7752e-03
Normally I would use the most recent version (both R and drc library)
but it seems to me that a standard error of 0.4 on a mean of 1.2 is too 
big, so I trust the values we get with the older versions more
Has anyone suggestions on
- how to solve these discrepancies, if possible
- how to calculate which one of the 2 solutions is the correct one?

Thanks a lot,
Hans Vermeiren

Demo (on a windows machine, while the issue was actually discovered on
our ubuntu linux server):
1)
sessionInfo()
R version 2.7.0 (2008-04-22)
i386-pc-mingw32

locale:
LC_COLLATE=Dutch_Belgium.1252;LC_CTYPE=Dutch_Belgium. 1252;LC_MONETARY=Du 
tch_Belgium.1252;LC_NUMERIC=C;LC_TIME=Dutch_Belgium.1252

attached base packages:
[1] stats     graphics  grDevices utils     datasets  methods   base


other attached packages:
[1] drc_1.4-2      plotrix_2.4-2  nlme_3.1-89    MASS_7.2-41
lattice_0.17-6
[6] alr3_1.1.7

loaded via a namespace (and not attached):
[1] grid_2.7.0

d<-data.frame(dose=c(2.00e-05, 4.00e-06, 8.00e-07, 1.60e-07, 3.20e-08,
6.40e-09, 1.28e-09, 2.56e-10, 5.10e-11, 1.00e-11, 2.00e-05, 4.00e-06,
8.00e-07, 1.60e-07, 3.20e-08, 6.40e-09, 1.28e-09, 2.56e-10, 5.10e-11,
1.00e-11),
response=c(97.202,81.670,47.292,16.924, 16.832,  6.832,  11.118,
1.319,   5.495,  -3.352, 102.464,  83.114,  50.631,  22.792,  18.348,
19.066,  27.794,  14.682,  11.992,  12.868))

m<- drm(response ~ (log10(dose*1e6)), data = d, fct = l4(fixed =
c(NA,NA,NA,NA), names = c("hs", "bottom", "top", "ec50")), logDose = 10, 
control = drmc(useD = T))

summary(m)
results in:
Model fitted: Log-logistic (ED50 as parameter) (4 parms)

Parameter estimates:

                     Estimate  Std. Error     t-value   p-value
hs:(Intercept)     -9.8065e-01  2.5821e-03 -3.7979e+02 2.248e-33
bottom:(Intercept)  1.0955e+01  2.2546e-02  4.8591e+02 4.364e-35
top:(Intercept)     1.0502e+02  9.0935e-02  1.1549e+03 4.210e-41
ec50:(Intercept)    1.2039e+00  3.7752e-03  3.1890e+02 3.681e-32

Residual standard error: 7.026655 (16 degrees of freedom)
= = ====================================================================== 
===========================================
2)
sessionInfo()
R version 2.9.0 (2009-04-17)
i386-pc-mingw32

locale:
LC_COLLATE=Dutch_Belgium.1252;LC_CTYPE=Dutch_Belgium. 1252;LC_MONETARY=Du 
tch_Belgium.1252;LC_NUMERIC=C;LC_TIME=Dutch_Belgium.1252

attached base packages:
[1] stats     graphics  grDevices utils     datasets  methods   base


other attached packages:
[1] drc_1.6-3       plotrix_2.5-5   nlme_3.1-90     MASS_7.2-46
magic_1.4-4     abind_1.1-0     lattice_0.17-22 alr3_1.1.7

loaded via a namespace (and not attached):
[1] grid_2.9.0  tools_2.9.0

d<-data.frame(dose=c(2.00e-05, 4.00e-06, 8.00e-07, 1.60e-07, 3.20e-08,
6.40e-09, 1.28e-09, 2.56e-10, 5.10e-11, 1.00e-11, 2.00e-05, 4.00e-06,
8.00e-07, 1.60e-07, 3.20e-08, 6.40e-09, 1.28e-09, 2.56e-10, 5.10e-11,
1.00e-11),
response=c(97.202,81.670,47.292,16.924, 16.832,  6.832,  11.118,
1.319,   5.495,  -3.352, 102.464,  83.114,  50.631,  22.792,  18.348,
19.066,  27.794,  14.682,  11.992,  12.868))

m<- drm(response ~ (log10(dose*1e6)), data = d, fct = l4(fixed =
c(NA,NA,NA,NA), names = c("hs", "bottom", "top", "ec50")), logDose = 10, 
control = drmc(useD = T))

summary(m)

gives:
Model fitted: Log-logistic (ED50 as parameter) (4 parms)

Parameter estimates:

                   Estimate Std. Error   t-value   p-value
hs:(Intercept)      -0.95266    0.25778  -3.69564    0.0020
bottom:(Intercept)  10.97437    2.24421   4.89009    0.0002
top:(Intercept)    106.38373    9.98378  10.65565 1.127e-08
ec50:(Intercept)     1.27447    0.43540   2.92712    0.0099

Residual standard error:

7.020175 (16 degrees of freedom)


Hans,
You have three important factors changing here. The version of R, the version of drc and the versions of any relevant drc dependencies (alr3, lattice, magic, MASS, nlme, plotrix).
I would first try to install the newer version of drc on the older R system (all else staying the same) and see what you get. Don't run update.packages() here, lest you change other things. Just install the newer version of drc.
If you get the same results as the older version, then it might lead you to something in R or one of the package dependencies changing.
If you get a different result, then it would lead to something in drc changing.
You can also install the old version of drc on your more recent R system to see what you get, which might help to confirm behavior. 

The old source version of drc would be available from:

  http://cran.r-project.org/src/contrib/Archive/drc/

I also found a Windows binary of the old package here:

  http://cran.r-project.org/bin/windows/contrib/2.6/drc_1.4-2.zip
I have also copied Christian Ritz, the drc package author/maintainer, so that he may be able to assist you further with the problem. 

HTH,

Marc Schwartz

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