[R] drc results differ for different versions

[Marc Schwartz]

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