insightrx/pkpdsim

Simulate PK-PD models defined as ODE systems

pkpdsim's Issues

Beginning Test Run

Hello
Im trying PKPDSim and ran the below code as in the site:
install.packages("PKPDsim")
library(PKPDsim)
library(ggplot2)

pk2 <- new_ode_model(
code = "dAdt[1] = -(CL/V) * A[1]",
obs = list(cmt = 1, scale = "V"),
dose = list(cmt = 1)
)
r2 <- new_regimen(
amt = 100,
n = 5,
interval = 12,
type = "infusion",
t_inf = 2
)
dat2 <- sim(
ode = pk2,
parameters = p,
regimen = r2,
only_obs = TRUE
)
ggplot(dat2, aes(x = t, y = y)) +
geom_line()

compared to the ones in the site

Can you help advice what is not right here please
Thank you
Jesmin

Interface with nlmixr (estimation)

Hi Ron,
I was wondering how well PKPDsim interfaces with nlmixr. I noticed your pkpdsim_to_nlmix() function accurately creates an nlmixr ui model to be fitted, given a simple model. PKPDsim provides more flexibility in model specification, such as allowing the specification of time varying covariates. I myself am having an issue just with creating fixed covariates with nlmixr while using the saem estimation method (this is a known issue with nlmixr and saem). I am assuming if the functionality was not implemented in nlmixr, but was with PKPDsim, the model will not translate well. I was hoping you could confirm or deny this, and if that is the case, have you utilized any other R packages for estimation that work well with PKPDsim?

Individual parameters

Hi,

First of all, thanks for maintaining this useful package.

I can't see from the documentation how to use individual parameters in a parameter table. I could do this in a loop or through the covariate table, but something tells me that it's just because I haven't found a more straightforward way.

Thanks!
Philip

Rcpp issue?

Hi Ron, I just installed the InsightRx/PKPDsim on a new macbook and I'm having issues with Rcpp when i try the new_ode_model() function. I am getting several errors like:

filecab22cab112.cpp:226:14: error: use of overloaded operator '=' is ambiguous (with operand types 'std::vector<double>' and 'Rcpp::Vector<19, PreserveStorage>::NameProxy' (aka 'generic_name_proxy<19, PreserveStorage>'))
  cov_FEMALE = design["cov_FEMALE"];
  ~~~~~~~~~~ ^ ~~~~~~~~~~~~~~~~~~~~
/Applications/Xcode.app/Contents/Developer/Toolchains/XcodeDefault.xctoolchain/usr/include/c++/v1/vector:574:13: note: candidate function
    vector& operator=(vector&& __x)

I have run the code on an older macbook/older PKPsim version and everything works fine. When I installed PKPDsim, I updated all packages (Rccp version 1.0.3) but I have also tried older Rcpp versions with no luck.

I've found this previous post which seems to be describing the same issue. Do you think there a similar problem with the compiler version? Please advise on how to fix. Thanks! #1

feature to simulate with uncertainty

perhaps best to write a separate function to handle the looping over drawn parameter sets, rather than have an additional argument to PKPDsim? sim_uncertainty()?

builtin multi-threaded simulations

I am getting Rcpp operator overloading issue n R 3.6.0, but it is fine R 3.4.2

Hi team,

I am trying to load a simple ode model provided in the docs page (covariates page). But I am getting an operator overloading issue between Rcpp::vector and std::vector in R 3.6.

When I try the same example in R 3.4.2, it works fine.

Could you please help me understand if there is a R version dependency and is that expected?

Thanks,
Thomas

If else statements within a differential equation

Dear @ronkeizer,
Can you please advise how would one try to write an ODE with an if/else statement in PKPDsim? I'm trying to write the following from Berkeley Madonna but not sure about the syntax/structure in PKPDsim...
Thanks in advance,
Mohamed

d/dt(Imax_FLT3) =
IF (C_FLT3>KC50_FLT3) THEN kdes * (1 - Imax_FLT3 * (1 + fu_FLT3 * C_FLT3/KC50_FLT3 )) ELSE kdes * (1 - Imax_FLT3 * (1 - fu_FLT3 * C_FLT3/KC50_FLT3 ))

Error with gcc-7.2

Dear PKPDSim creators,

thank you loads for a most useful package. With current versions of gcc-7.2 and stdlib, I ran into an error message. Using the introductory example

p <- list(CL = 1, V = 10, KA = 0.5)
pk1 <- new_ode_model("pk_1cmt_oral")

led to the following list of error messages, each one nagging at ambiguous overload operators:

file4b7eba8cc03.cpp: In Funktion »Rcpp::List sim_wrapper_cpp(Rcpp::NumericVector, Rcpp::List, Rcpp::List, Rcpp::NumericVector, double)«:
file4b7eba8cc03.cpp:89:21: Fehler: ambiguous overload for »operator=« (operand types are »std::vector« and »Rcpp::Vector<19>::NameProxy {aka Rcpp::internal::generic_name_proxy<19>}«)
times = design["t"];
^
In file included from /usr/include/c++/7/vector:69:0,
from /usr/local/lib64/R/library/Rcpp/include/RcppCommon.h:59,
from /usr/local/lib64/R/library/Rcpp/include/Rcpp.h:27,
from file4b7eba8cc03.cpp:8:
/usr/include/c++/7/bits/vector.tcc:179:5: Anmerkung: candidate: std::vector<_Tp, _Alloc>& std::vector<_Tp, _Alloc>::operator=(const std::vector<_Tp, _Alloc>&) [with _Tp = double; _Alloc = std::allocator]
vector<_Tp, _Alloc>::
^~~~~~~~~~~~~~~~~~~
In file included from /usr/include/c++/7/vector:64:0,
from /usr/local/lib64/R/library/Rcpp/include/RcppCommon.h:59,
from /usr/local/lib64/R/library/Rcpp/include/Rcpp.h:27,
from file4b7eba8cc03.cpp:8:
/usr/include/c++/7/bits/stl_vector.h:461:7: Anmerkung: candidate: std::vector<_Tp, _Alloc>& std::vector<_Tp, _Alloc>::operator=(std::vector<_Tp, _Alloc>&&) [with _Tp = double; _Alloc = std::allocator]
operator=(vector&& __x) noexcept(_Alloc_traits::_S_nothrow_move())
^~~~~~~~
/usr/include/c++/7/bits/stl_vector.h:482:7: Anmerkung: candidate: std::vector<_Tp, _Alloc>& std::vector<_Tp, _Alloc>::operator=(std::initializer_list<_Tp>) [with _Tp = double; _Alloc = std::allocator]
operator=(initializer_list<value_type> __l)
^~~~~~~~
file4b7eba8cc03.cpp:90:24: Fehler: ambiguous overload for »operator=« (operand types are »std::vector« and »Rcpp::Vector<19>::NameProxy {aka Rcpp::internal::generic_name_proxy<19>}«)
doses = design["dose"];
^
In file included from /usr/include/c++/7/vector:69:0,
from /usr/local/lib64/R/library/Rcpp/include/RcppCommon.h:59,
from /usr/local/lib64/R/library/Rcpp/include/Rcpp.h:27,
from file4b7eba8cc03.cpp:8:
/usr/include/c++/7/bits/vector.tcc:179:5: Anmerkung: candidate: std::vector<_Tp, _Alloc>& std::vector<_Tp, _Alloc>::operator=(const std::vector<_Tp, _Alloc>&) [with _Tp = double; _Alloc = std::allocator]
vector<_Tp, _Alloc>::
^~~~~~~~~~~~~~~~~~~
In file included from /usr/include/c++/7/vector:64:0,
from /usr/local/lib64/R/library/Rcpp/include/RcppCommon.h:59,
from /usr/local/lib64/R/library/Rcpp/include/Rcpp.h:27,
from file4b7eba8cc03.cpp:8:
/usr/include/c++/7/bits/stl_vector.h:461:7: Anmerkung: candidate: std::vector<_Tp, _Alloc>& std::vector<_Tp, _Alloc>::operator=(std::vector<_Tp, _Alloc>&&) [with _Tp = double; _Alloc = std::allocator]
operator=(vector&& __x) noexcept(_Alloc_traits::_S_nothrow_move())
^~~~~~~~
/usr/include/c++/7/bits/stl_vector.h:482:7: Anmerkung: candidate: std::vector<_Tp, _Alloc>& std::vector<_Tp, _Alloc>::operator=(std::initializer_list<_Tp>) [with _Tp = double; _Alloc = std::allocator]
operator=(initializer_list<value_type> __l)
^~~~~~~~
file4b7eba8cc03.cpp:91:23: Fehler: ambiguous overload for »operator=« (operand types are »std::vector« and »Rcpp::Vector<19>::NameProxy {aka Rcpp::internal::generic_name_proxy<19>}«)
evid = design["evid"];
^
In file included from /usr/include/c++/7/vector:69:0,
from /usr/local/lib64/R/library/Rcpp/include/RcppCommon.h:59,
from /usr/local/lib64/R/library/Rcpp/include/Rcpp.h:27,
from file4b7eba8cc03.cpp:8:
/usr/include/c++/7/bits/vector.tcc:179:5: Anmerkung: candidate: std::vector<_Tp, _Alloc>& std::vector<_Tp, _Alloc>::operator=(const std::vector<_Tp, _Alloc>&) [with _Tp = int; _Alloc = std::allocator]
vector<_Tp, _Alloc>::
^~~~~~~~~~~~~~~~~~~
In file included from /usr/include/c++/7/vector:64:0,
from /usr/local/lib64/R/library/Rcpp/include/RcppCommon.h:59,
from /usr/local/lib64/R/library/Rcpp/include/Rcpp.h:27,
from file4b7eba8cc03.cpp:8:
/usr/include/c++/7/bits/stl_vector.h:461:7: Anmerkung: candidate: std::vector<_Tp, _Alloc>& std::vector<_Tp, _Alloc>::operator=(std::vector<_Tp, _Alloc>&&) [with _Tp = int; _Alloc = std::allocator]
operator=(vector&& __x) noexcept(_Alloc_traits::_S_nothrow_move())
^~~~~~~~
/usr/include/c++/7/bits/stl_vector.h:482:7: Anmerkung: candidate: std::vector<_Tp, _Alloc>& std::vector<_Tp, _Alloc>::operator=(std::initializer_list<_Tp>) [with _Tp = int; _Alloc = std::allocator]
operator=(initializer_list<value_type> __l)
^~~~~~~~
file4b7eba8cc03.cpp:92:23: Fehler: ambiguous overload for »operator=« (operand types are »std::vector« and »Rcpp::Vector<19>::NameProxy {aka Rcpp::internal::generic_name_proxy<19>}«)
dummy = design["dum"];
^
In file included from /usr/include/c++/7/vector:69:0,
from /usr/local/lib64/R/library/Rcpp/include/RcppCommon.h:59,
from /usr/local/lib64/R/library/Rcpp/include/Rcpp.h:27,
from file4b7eba8cc03.cpp:8:
/usr/include/c++/7/bits/vector.tcc:179:5: Anmerkung: candidate: std::vector<_Tp, _Alloc>& std::vector<_Tp, _Alloc>::operator=(const std::vector<_Tp, _Alloc>&) [with _Tp = double; _Alloc = std::allocator]
vector<_Tp, _Alloc>::
^~~~~~~~~~~~~~~~~~~
In file included from /usr/include/c++/7/vector:64:0,
from /usr/local/lib64/R/library/Rcpp/include/RcppCommon.h:59,
from /usr/local/lib64/R/library/Rcpp/include/Rcpp.h:27,
from file4b7eba8cc03.cpp:8:
/usr/include/c++/7/bits/stl_vector.h:461:7: Anmerkung: candidate: std::vector<_Tp, _Alloc>& std::vector<_Tp, _Alloc>::operator=(std::vector<_Tp, _Alloc>&&) [with _Tp = double; _Alloc = std::allocator]
operator=(vector&& __x) noexcept(_Alloc_traits::_S_nothrow_move())
^~~~~~~~
/usr/include/c++/7/bits/stl_vector.h:482:7: Anmerkung: candidate: std::vector<_Tp, _Alloc>& std::vector<_Tp, _Alloc>::operator=(std::initializer_list<_Tp>) [with _Tp = double; _Alloc = std::allocator]
operator=(initializer_list<value_type> __l)
^~~~~~~~
file4b7eba8cc03.cpp:93:24: Fehler: ambiguous overload for »operator=« (operand types are »std::vector« and »Rcpp::Vector<19>::NameProxy {aka Rcpp::internal::generic_name_proxy<19>}«)
rates = design["rate"];
^
In file included from /usr/include/c++/7/vector:69:0,
from /usr/local/lib64/R/library/Rcpp/include/RcppCommon.h:59,
from /usr/local/lib64/R/library/Rcpp/include/Rcpp.h:27,
from file4b7eba8cc03.cpp:8:
/usr/include/c++/7/bits/vector.tcc:179:5: Anmerkung: candidate: std::vector<_Tp, _Alloc>& std::vector<_Tp, _Alloc>::operator=(const std::vector<_Tp, _Alloc>&) [with _Tp = double; _Alloc = std::allocator]
vector<_Tp, _Alloc>::
^~~~~~~~~~~~~~~~~~~
In file included from /usr/include/c++/7/vector:64:0,
from /usr/local/lib64/R/library/Rcpp/include/RcppCommon.h:59,
from /usr/local/lib64/R/library/Rcpp/include/Rcpp.h:27,
from file4b7eba8cc03.cpp:8:
/usr/include/c++/7/bits/stl_vector.h:461:7: Anmerkung: candidate: std::vector<_Tp, _Alloc>& std::vector<_Tp, _Alloc>::operator=(std::vector<_Tp, _Alloc>&&) [with _Tp = double; _Alloc = std::allocator]
operator=(vector&& __x) noexcept(_Alloc_traits::_S_nothrow_move())
^~~~~~~~
/usr/include/c++/7/bits/stl_vector.h:482:7: Anmerkung: candidate: std::vector<_Tp, _Alloc>& std::vector<_Tp, _Alloc>::operator=(std::initializer_list<_Tp>) [with _Tp = double; _Alloc = std::allocator]
operator=(initializer_list<value_type> __l)
^~~~~~~~
file4b7eba8cc03.cpp:94:31: Fehler: ambiguous overload for »operator=« (operand types are »std::vector« and »Rcpp::Vector<19>::NameProxy {aka Rcpp::internal::generic_name_proxy<19>}«)
dose_cmt = design["dose_cmt"];
^
In file included from /usr/include/c++/7/vector:69:0,
from /usr/local/lib64/R/library/Rcpp/include/RcppCommon.h:59,
from /usr/local/lib64/R/library/Rcpp/include/Rcpp.h:27,
from file4b7eba8cc03.cpp:8:
/usr/include/c++/7/bits/vector.tcc:179:5: Anmerkung: candidate: std::vector<_Tp, _Alloc>& std::vector<_Tp, _Alloc>::operator=(const std::vector<_Tp, _Alloc>&) [with _Tp = int; _Alloc = std::allocator]
vector<_Tp, _Alloc>::
^~~~~~~~~~~~~~~~~~~
In file included from /usr/include/c++/7/vector:64:0,
from /usr/local/lib64/R/library/Rcpp/include/RcppCommon.h:59,
from /usr/local/lib64/R/library/Rcpp/include/Rcpp.h:27,
from file4b7eba8cc03.cpp:8:
/usr/include/c++/7/bits/stl_vector.h:461:7: Anmerkung: candidate: std::vector<_Tp, _Alloc>& std::vector<_Tp, _Alloc>::operator=(std::vector<_Tp, _Alloc>&&) [with _Tp = int; _Alloc = std::allocator]
operator=(vector&& __x) noexcept(_Alloc_traits::_S_nothrow_move())
^~~~~~~~
/usr/include/c++/7/bits/stl_vector.h:482:7: Anmerkung: candidate: std::vector<_Tp, _Alloc>& std::vector<_Tp, _Alloc>::operator=(std::initializer_list<_Tp>) [with _Tp = int; _Alloc = std::allocator]
operator=(initializer_list<value_type> __l)
^~~~~~~~
file4b7eba8cc03.cpp:95:28: Fehler: ambiguous overload for »operator=« (operand types are »std::vector« and »Rcpp::Vector<19>::NameProxy {aka Rcpp::internal::generic_name_proxy<19>}«)
dose_type = design["type"];
^
In file included from /usr/include/c++/7/vector:69:0,
from /usr/local/lib64/R/library/Rcpp/include/RcppCommon.h:59,
from /usr/local/lib64/R/library/Rcpp/include/Rcpp.h:27,
from file4b7eba8cc03.cpp:8:
/usr/include/c++/7/bits/vector.tcc:179:5: Anmerkung: candidate: std::vector<_Tp, _Alloc>& std::vector<_Tp, _Alloc>::operator=(const std::vector<_Tp, _Alloc>&) [with _Tp = int; _Alloc = std::allocator]
vector<_Tp, _Alloc>::
^~~~~~~~~~~~~~~~~~~
In file included from /usr/include/c++/7/vector:64:0,
from /usr/local/lib64/R/library/Rcpp/include/RcppCommon.h:59,
from /usr/local/lib64/R/library/Rcpp/include/Rcpp.h:27,
from file4b7eba8cc03.cpp:8:
/usr/include/c++/7/bits/stl_vector.h:461:7: Anmerkung: candidate: std::vector<_Tp, _Alloc>& std::vector<_Tp, _Alloc>::operator=(std::vector<_Tp, _Alloc>&&) [with _Tp = int; _Alloc = std::allocator]
operator=(vector&& __x) noexcept(_Alloc_traits::_S_nothrow_move())
^~~~~~~~
/usr/include/c++/7/bits/stl_vector.h:482:7: Anmerkung: candidate: std::vector<_Tp, _Alloc>& std::vector<_Tp, _Alloc>::operator=(std::initializer_list<_Tp>) [with _Tp = int; _Alloc = std::allocator]
operator=(initializer_list<value_type> __l)
^~~~~~~~
make: *** [file4b7eba8cc03.o] Fehler 1
g++ -I/usr/local/lib64/R/include -DNDEBUG -I"/usr/local/lib64/R/library/Rcpp/include" -I"/usr/local/lib64/R/library/BH/include" -I"/tmp/RtmpD8fySg/sourceCpp-x86_64-pc-linux-gnu-0.12.13" -I/usr/local/include -w -fpic -g -O2 -c file4b7eba8cc03.cpp -o file4b7eba8cc03.o
/usr/local/lib64/R/etc/Makeconf:166: die Regel für Ziel „file4b7eba8cc03.o“ scheiterte
Fehler in Rcpp::sourceCpp(code = sim_func, rebuild = TRUE, env = globalenv(), :
Error 1 occurred building shared library.

Issue with making a model with new_ode_model()

The new_ode_model() function seems to be broken for me. I am using R 4.2.1 ? Is this potentially the issue?

 pk1 <- new_ode_model(model = "pk_1cmt_oral")
Error in if (txt < 0) return(ode_def_orig) : the condition has length > 1
> pk1 <- new_ode_model(code = "
+   dAdt[1] = -KA * A[1]
+   dAdt[2] = +KA * A[1] -(CL/V) * A[2]
+ ")
Error in if (txt < 0) return(ode_def_orig) : the condition has length > 1

How do you do a PKPD indrect response simulation?

Hi Ron,

I am trying to figure out how to simulate PK-IDR. Your documentation doesn't show much details. Also, I ran the example you provided, and was wondering how you can see/plot the Effect values at the same time as Conc vs Time; on same plot or separate plots?

-Ken

nlmixr package - saem and nlme function issue

Hi,

I have installed the nlmixr package. However when i try to run a code based on the package, i receive error on saem.

Also, i tested the package installation using the file provided by the nlmixr package developer. "https://raw.githubusercontent.com/nlmixrdevelopment/nlmixr/master/build/test_install.R".

When i source the above file, i receive the above error:

source("test_install.R")
Correct R version: Yes, R version 3.6.0 (2019-04-26)
RxODE installed: Yes
Python installed: Yes, Python 3.6.8
sympy installed: Yes
devtools package installed: Yes
RxODE package installed: Yes
Rtools installed or not needed: Yes
SnakeCharmR package installed: Yes
units package installed: Yes
nlmixr package installed: Yes
xpose.nlmixr package installed: Yes
shinyMixR package installed: Yes
Running nlme
Running saem
Error : Error building SAEM model

Could you please let me know what is the exact issue and how could i resolve it?

Best Regards,
Thomas

Simulate effect of a time-varying categorical covariate

Dear Ron,
I am trying to do a simple simulation for a cross-over trial where in period 1 multiple doses of Drug X alone (or under fasting condition) are administered. In period 2, multiple doses of Drug X are administered in combination with a another conmed (or with food). How can I code the off/on switch of the drug-drug or drug-food interactions (basically being silent in Period 1 and then active in Period 2)?
Thanks for your reply in advance...
Mohamed

Problems creating new_ode model

Hi guys,

I want to create a one compartment model with first order absorption and elimination (drug administered orally). I want the model to contain bioavailabilty and half life time and to be able to show concentrations and to predict time to reach steady state.

I first tried to model it like this (without halflife time):

par_mod_BA<-list(KA=1, KEL=0.6, F=0.98)
reg_mod_BA<-new_regimen(
amt=400,
interval=24,
n=5
)
mod_BA<-new_ode_model(
code="
dAdt[1]=-KAA[1];
dAdt[2]=KAA[1]-KEL*A[2]",
dose=list(cmt=1, bioav="F"),
obs=list(cmt=2),
parameters=c("F","KEL", "KA")
)

My questions is:
I want to include half life time "HLT", that can be described by the term HLT=ln(2)/KEL, KEL=ln(2)/HLT respectively. I tried it by making HLT a covariate.

cov1<-list("HLT"=new_covariate(value=17))

par_mod_BA<-list(KA=1, KEL=0.6, F=0.98)

reg_mod_BA<-new_regimen(
amt=400,
interval=24,
n=5
)

mod_BA_HLT<-new_ode_model(
code="
dAdt[1]=-KAA[1];
dAdt[2]=KAA[1]-KEL*A[2];
KEL=log(2)/HLT",
declare_variables=c("KEL","KA"),
covariates=cov1
)

data_mod_BA_HLT<-sim_ode(ode=mod_BA_HLT,
regimen=reg_mod_BA,
parameters=par_mod_BA)

But when I try to run the simulation is says:
Error in sim(...) :
Not all covariates for this model have been specified. Missing:
HLT

but I don't understand because I specified it in my opinion. I tried to fix it but I can't figure out what I am doing wrong...

Thank you so much for any help!:)

issue with new_ode_model: Create new ODE model

I'm trying to create an ODE model with sin and cos and it is not working