Error with fitting using simulated data

Estimation
1

Hello Everyone, I have the following model where I simulated a dataset from:

using Pumas
using Distributions
using Random
using CSV
disease_drug = @model begin
    @param begin
      θbaseline  ∈ RealDomain()
      θPmax      ∈ RealDomain()
      θTD        ∈ RealDomain()
      θPOW       ∈ RealDomain()
      θEmax      ∈ RealDomain()
      θEC50      ∈ RealDomain()
      θKt        ∈ RealDomain()
      Ω_1        ∈ PDiagDomain(6)
      σ_add      ∈ RealDomain()
    end

    @random begin
        η_1 ~ MvNormal(Ω_1)
      end

    @covariates Cavg

    @pre begin
      baseline    = θbaseline * exp(η_1[1])
      Pmax        = θPmax   + η_1[3]
      TD          = θTD    * exp(η_1[2])
      POW         = θPOW    + η_1[4]
      Emax        = θEmax  * exp(η_1[5])
      EC50        = θEC50  * exp(η_1[6])
      Kt          = θKt
      average      = Cavg 
    end

    @vars begin
        Placebo = (Pmax*(1 .- exp(.-(t/TD))^POW))
        Drug = ((Emax*average)/(EC50+average))
        Delay = (1 .- exp(.-(Kt.*t)))
    end
    @derived begin
      PANSS = baseline .* (1 .- (Placebo)) .* (1 .- (Drug*Delay))
      Observed ~ @. Normal(PANSS,σ_add)
    end
  end


param_peds = (
        θbaseline = 93.3,
        θPmax = 0.14,
        θTD = 3.6,
        θPOW = 1.68,
        θEmax = 0.07,
        θEC50 = 0.006,
        θKt = 0.52,
        Ω_1  = Diagonal([0.03,0.05,0.06,0.67,0.74,0.9]),
        σ_add = 4.99
        )
Random.seed!(1234)
choose_covariates_2() = (Cavg = rand(Uniform(0, 0.042)),)
pop_peds = map(i -> Subject(id = i,
                                      #events = dose,
                                      covariates = choose_covariates_1()), 1:326) 
sim_peds = DataFrame(simobs(disease_drug,pop_peds,param_peds, obstimes = 0:1:6))

peds = read_pumas(sim_peds, id = :id, time = :time, observations = [:Observed], covariates = [:Cavg], event_data = false)

fit_peds = fit(disease_drug,peds,param_peds,Pumas.FOCEI())

I am trying to estimate the parameters from the simulated dataset but I am getting the following error and I am not able to interpret it

ERROR: MethodError: no method matching *(::Vector{ForwardDiff.Dual{ForwardDiff.Tag{Pumas.var"#407#408"{PumasModel{ParamSet{NamedTuple{(:θbaseline, :θPmax, :θTD, :θPOW, :θEmax, :θEC50, :θKt, :Ω_1, :σ_add), Tuple{RealDomain{TransformVariables.Infinity{false}, TransformVariables.Infinity{true}, Float64}, RealDomain{TransformVariables.Infinity{false}, TransformVariables.Infinity{true}, Float64}, RealDomain{TransformVariables.Infinity{false}, TransformVariables.Infinity{true}, Float64}, RealDomain{TransformVariables.Infinity{false}, TransformVariables.Infinity{true}, Float64}, RealDomain{TransformVariables.Infinity{false}, TransformVariables.Infinity{true}, Float64}, RealDomain{TransformVariables.Infinity{false}, TransformVariables.Infinity{true}, Float64}, RealDomain{TransformVariables.Infinity{false}, TransformVariables.Infinity{true}, Float64}, PDiagDomain{PDMats.PDiagMat{Float64, Vector{Float64}}}, RealDomain{TransformVariables.Infinity{false}, TransformVariables.Infinity{true}, Float64}}}}, var"#877#901", var"#878#902", var"#880#904", var"#882#906", Nothing, var"#883#907", var"#892#916", Nothing}, Subject{NamedTuple{(:Observed,), Tuple{Vector{Union{Missing, Float64}}}}, Pumas.ConstantCovar{NamedTuple{(:Cavg,), Tuple{Float64}}}, Vector{Pumas.Event{Float64, Float64, Float64, Float64, Float64, Float64, Int64}}, Vector{Float64}}, NamedTuple{(:θbaseline, :θPmax, :θTD, :θPOW, :θEmax, :θEC50, :θKt, :Ω_1, :σ_add), Tuple{Float64, Float64, Float64, Float64, Float64, Float64, Float64, PDMats.PDiagMat{Float64, Vector{Float64}}, Float64}}, NamedTuple{(:obstimes,), Tuple{Nothing}}}, Float64}, Float64, 6}}, ::Vector{Float64})
Closest candidates are:
  *(::Any, ::Any, ::Any, ::Any...) at operators.jl:560
  *(::StridedMatrix{T}, ::StridedVector{S}) where {T<:Union{Float32, Float64, ComplexF32, ComplexF64}, S<:Real} at /usr/local/julia/share/julia/stdlib/v1.6/LinearAlgebra/src/matmul.jl:44
  *(::StridedVecOrMat{T} where T, ::LinearAlgebra.LQPackedQ) at /usr/local/julia/share/julia/stdlib/v1.6/LinearAlgebra/src/lq.jl:278
  ...
Stacktrace:
  [1] (::var"#883#907")(_pre::Pumas.Pre{Nothing, var"#879#903"{NamedTuple{(:θbaseline, :θPmax, :θTD, :θPOW, :θEmax, :θEC50, :θKt, :Ω_1, :σ_add), Tuple{Float64, Float64, Float64, Float64, Float64, Float64, Float64, PDMats.PDiagMat{Float64, Vector{Float64}}, Float64}}, NamedTuple{(:η_1,), Tuple{Vector{ForwardDiff.Dual{ForwardDiff.Tag{Pumas.var"#407#408"{PumasModel{ParamSet{NamedTuple{(:θbaseline, :θPmax, :θTD, :θPOW, :θEmax, :θEC50, :θKt, :Ω_1, :σ_add), Tuple{RealDomain{TransformVariables.Infinity{false}, TransformVariables.Infinity{true}, Float64}, RealDomain{TransformVariables.Infinity{false}, TransformVariables.Infinity{true}, Float64}, RealDomain{TransformVariables.Infinity{false}, TransformVariables.Infinity{true}, Float64}, RealDomain{TransformVariables.Infinity{false}, TransformVariables.Infinity{true}, Float64}, RealDomain{TransformVariables.Infinity{false}, TransformVariables.Infinity{true}, Float64}, RealDomain{TransformVariables.Infinity{false}, TransformVariables.Infinity{true}, Float64}, RealDomain{TransformVariables.Infinity{false}, TransformVariables.Infinity{true}, Float64}, PDiagDomain{PDMats.PDiagMat{Float64, Vector{Float64}}}, RealDomain{TransformVariables.Infinity{false}, TransformVariables.Infinity{true}, Float64}}}}, var"#877#901", var"#878#902", var"#880#904", var"#882#906", Nothing, var"#883#907", var"#892#916", Nothing}, Subject{NamedTuple{(:Observed,), Tuple{Vector{Union{Missing, Float64}}}}, Pumas.ConstantCovar{NamedTuple{(:Cavg,), Tuple{Float64}}}, Vector{Pumas.Event{Float64, Float64, Float64, Float64, Float64, Float64, Int64}}, Vector{Float64}}, NamedTuple{(:θbaseline, :θPmax, :θTD, :θPOW, :θEmax, :θEC50, :θKt, :Ω_1, :σ_add), Tuple{Float64, Float64, Float64, Float64, Float64, Float64, Float64, PDMats.PDiagMat{Float64, Vector{Float64}}, Float64}}, NamedTuple{(:obstimes,), Tuple{Nothing}}}, Float64}, Float64, 6}}}}, Subject{NamedTuple{(:Observed,), Tuple{Vector{Union{Missing, Float64}}}}, Pumas.ConstantCovar{NamedTuple{(:Cavg,), Tuple{Float64}}}, Vector{Pumas.Event{Float64, Float64, Float64, Float64, Float64, Float64, Int64}}, Vector{Float64}}}}, _sol::Nothing, _obstimes::Vector{Float64}, _subject::Subject{NamedTuple{(:Observed,), Tuple{Vector{Union{Missing, Float64}}}}, Pumas.ConstantCovar{NamedTuple{(:Cavg,), Tuple{Float64}}}, Vector{Pumas.Event{Float64, Float64, Float64, Float64, Float64, Float64, Int64}}, Vector{Float64}}, _param::NamedTuple{(:θbaseline, :θPmax, :θTD, :θPOW, :θEmax, :θEC50, :θKt, :Ω_1, :σ_add), Tuple{Float64, Float64, Float64, Float64, Float64, Float64, Float64, PDMats.PDiagMat{Float64, Vector{Float64}}, Float64}}, _random::NamedTuple{(:η_1,), Tuple{Vector{ForwardDiff.Dual{ForwardDiff.Tag{Pumas.var"#407#408"{PumasModel{ParamSet{NamedTuple{(:θbaseline, :θPmax, :θTD, :θPOW, :θEmax, :θEC50, :θKt, :Ω_1, :σ_add), Tuple{RealDomain{TransformVariables.Infinity{false}, TransformVariables.Infinity{true}, Float64}, RealDomain{TransformVariables.Infinity{false}, TransformVariables.Infinity{true}, Float64}, RealDomain{TransformVariables.Infinity{false}, TransformVariables.Infinity{true}, Float64}, RealDomain{TransformVariables.Infinity{false}, TransformVariables.Infinity{true}, Float64}, RealDomain{TransformVariables.Infinity{false}, TransformVariables.Infinity{true}, Float64}, RealDomain{TransformVariables.Infinity{false}, TransformVariables.Infinity{true}, Float64}, RealDomain{TransformVariables.Infinity{false}, TransformVariables.Infinity{true}, Float64}, PDiagDomain{PDMats.PDiagMat{Float64, Vector{Float64}}}, RealDomain{TransformVariables.Infinity{false}, TransformVariables.Infinity{true}, Float64}}}}, var"#877#901", var"#878#902", var"#880#904", var"#882#906", Nothing, var"#883#907", var"#892#916", Nothing}, Subject{NamedTuple{(:Observed,), Tuple{Vector{Union{Missing, Float64}}}}, Pumas.ConstantCovar{NamedTuple{(:Cavg,), Tuple{Float64}}}, Vector{Pumas.Event{Float64, Float64, Float64, Float64, Float64, Float64, Int64}}, Vector{Float64}}, NamedTuple{(:θbaseline, :θPmax, :θTD, :θPOW, :θEmax, :θEC50, :θKt, :Ω_1, :σ_add), Tuple{Float64, Float64, Float64, Float64, Float64, Float64, Float64, PDMats.PDiagMat{Float64, Vector{Float64}}, Float64}}, NamedTuple{(:obstimes,), Tuple{Nothing}}}, Float64}, Float64, 6}}}})
    @ Main /builds/PumasAI/PumasSystemImages-jl/.julia/packages/Pumas/HDuXQ/src/dsl/model_macro.jl:929
  [2] #_derived#245
    @ /builds/PumasAI/PumasSystemImages-jl/.julia/packages/Pumas/HDuXQ/src/models/model_api.jl:858 [inlined]
  [3] (::Pumas.var"#407#408"{PumasModel{ParamSet{NamedTuple{(:θbaseline, :θPmax, :θTD, :θPOW, :θEmax, :θEC50, :θKt, :Ω_1, :σ_add), Tuple{RealDomain{TransformVariables.Infinity{false}, TransformVariables.Infinity{true}, Float64}, RealDomain{TransformVariables.Infinity{false}, TransformVariables.Infinity{true}, Float64}, RealDomain{TransformVariables.Infinity{false}, TransformVariables.Infinity{true}, Float64}, RealDomain{TransformVariables.Infinity{false}, TransformVariables.Infinity{true}, Float64}, RealDomain{TransformVariables.Infinity{false}, TransformVariables.Infinity{true}, Float64}, RealDomain{TransformVariables.Infinity{false}, TransformVariables.Infinity{true}, Float64}, RealDomain{TransformVariables.Infinity{false}, TransformVariables.Infinity{true}, Float64}, PDiagDomain{PDMats.PDiagMat{Float64, Vector{Float64}}}, RealDomain{TransformVariables.Infinity{false}, TransformVariables.Infinity{true}, Float64}}}}, var"#877#901", var"#878#902", var"#880#904", var"#882#906", Nothing, var"#883#907", var"#892#916", Nothing}, Subject{NamedTuple{(:Observed,), Tuple{Vector{Union{Missing, Float64}}}}, Pumas.ConstantCovar{NamedTuple{(:Cavg,), Tuple{Float64}}}, Vector{Pumas.Event{Float64, Float64, Float64, Float64, Float64, Float64, Int64}}, Vector{Float64}}, NamedTuple{(:θbaseline, :θPmax, :θTD, :θPOW, :θEmax, :θEC50, :θKt, :Ω_1, :σ_add), Tuple{Float64, Float64, Float64, Float64, Float64, Float64, Float64, PDMats.PDiagMat{Float64, Vector{Float64}}, Float64}}, NamedTuple{(:obstimes,), Tuple{Nothing}}})(vηorth::Vector{ForwardDiff.Dual{ForwardDiff.Tag{Pumas.var"#407#408"{PumasModel{ParamSet{NamedTuple{(:θbaseline, :θPmax, :θTD, :θPOW, :θEmax, :θEC50, :θKt, :Ω_1, :σ_add), Tuple{RealDomain{TransformVariables.Infinity{false}, TransformVariables.Infinity{true}, Float64}, RealDomain{TransformVariables.Infinity{false}, TransformVariables.Infinity{true}, Float64}, RealDomain{TransformVariables.Infinity{false}, TransformVariables.Infinity{true}, Float64}, RealDomain{TransformVariables.Infinity{false}, TransformVariables.Infinity{true}, Float64}, RealDomain{TransformVariables.Infinity{false}, TransformVariables.Infinity{true}, Float64}, RealDomain{TransformVariables.Infinity{false}, TransformVariables.Infinity{true}, Float64}, RealDomain{TransformVariables.Infinity{false}, TransformVariables.Infinity{true}, Float64}, PDiagDomain{PDMats.PDiagMat{Float64, Vector{Float64}}}, RealDomain{TransformVariables.Infinity{false}, TransformVariables.Infinity{true}, Float64}}}}, var"#877#901", var"#878#902", var"#880#904", var"#882#906", Nothing, var"#883#907", var"#892#916", Nothing}, Subject{NamedTuple{(:Observed,), Tuple{Vector{Union{Missing, Float64}}}}, Pumas.ConstantCovar{NamedTuple{(:Cavg,), Tuple{Float64}}}, Vector{Pumas.Event{Float64, Float64, Float64, Float64, Float64, Float64, Int64}}, Vector{Float64}}, NamedTuple{(:θbaseline, :θPmax, :θTD, :θPOW, :θEmax, :θEC50, :θKt, :Ω_1, :σ_add), Tuple{Float64, Float64, Float64, Float64, Float64, Float64, Float64, PDMats.PDiagMat{Float64, Vector{Float64}}, Float64}}, NamedTuple{(:obstimes,), Tuple{Nothing}}}, Float64}, Float64, 6}})
    @ Pumas /builds/PumasAI/PumasSystemImages-jl/.julia/packages/Pumas/HDuXQ/src/estimation/likelihoods.jl:1637
  [4] _derived_vηorth_gradient(m::PumasModel{ParamSet{NamedTuple{(:θbaseline, :θPmax, :θTD, :θPOW, :θEmax, :θEC50, :θKt, :Ω_1, :σ_add), Tuple{RealDomain{TransformVariables.Infinity{false}, TransformVariables.Infinity{true}, Float64}, RealDomain{TransformVariables.Infinity{false}, TransformVariables.Infinity{true}, Float64}, RealDomain{TransformVariables.Infinity{false}, TransformVariables.Infinity{true}, Float64}, RealDomain{TransformVariables.Infinity{false}, TransformVariables.Infinity{true}, Float64}, RealDomain{TransformVariables.Infinity{false}, TransformVariables.Infinity{true}, Float64}, RealDomain{TransformVariables.Infinity{false}, TransformVariables.Infinity{true}, Float64}, RealDomain{TransformVariables.Infinity{false}, TransformVariables.Infinity{true}, Float64}, PDiagDomain{PDMats.PDiagMat{Float64, Vector{Float64}}}, RealDomain{TransformVariables.Infinity{false}, TransformVariables.Infinity{true}, Float64}}}}, var"#877#901", var"#878#902", var"#880#904", var"#882#906", Nothing, var"#883#907", var"#892#916", Nothing}, subject::Subject{NamedTuple{(:Observed,), Tuple{Vector{Union{Missing, Float64}}}}, Pumas.ConstantCovar{NamedTuple{(:Cavg,), Tuple{Float64}}}, Vector{Pumas.Event{Float64, Float64, Float64, Float64, Float64, Float64, Int64}}, Vector{Float64}}, param::NamedTuple{(:θbaseline, :θPmax, :θTD, :θPOW, :θEmax, :θEC50, :θKt, :Ω_1, :σ_add), Tuple{Float64, Float64, Float64, Float64, Float64, Float64, Float64, PDMats.PDiagMat{Float64, Vector{Float64}}, Float64}}, vrandeffsorth::Vector{Float64}, diffeq_options::NamedTuple{(), Tuple{}})
    @ Pumas /builds/PumasAI/PumasSystemImages-jl/.julia/packages/Pumas/HDuXQ/src/estimation/likelihoods.jl:1644
  [5] _∂²l∂η²(m::PumasModel{ParamSet{NamedTuple{(:θbaseline, :θPmax, :θTD, :θPOW, :θEmax, :θEC50, :θKt, :Ω_1, :σ_add), Tuple{RealDomain{TransformVariables.Infinity{false}, TransformVariables.Infinity{true}, Float64}, RealDomain{TransformVariables.Infinity{false}, TransformVariables.Infinity{true}, Float64}, RealDomain{TransformVariables.Infinity{false}, TransformVariables.Infinity{true}, Float64}, RealDomain{TransformVariables.Infinity{false}, TransformVariables.Infinity{true}, Float64}, RealDomain{TransformVariables.Infinity{false}, TransformVariables.Infinity{true}, Float64}, RealDomain{TransformVariables.Infinity{false}, TransformVariables.Infinity{true}, Float64}, RealDomain{TransformVariables.Infinity{false}, TransformVariables.Infinity{true}, Float64}, PDiagDomain{PDMats.PDiagMat{Float64, Vector{Float64}}}, RealDomain{TransformVariables.Infinity{false}, TransformVariables.Infinity{true}, Float64}}}}, var"#877#901", var"#878#902", var"#880#904", var"#882#906", Nothing, var"#883#907", var"#892#916", Nothing}, subject::Subject{NamedTuple{(:Observed,), Tuple{Vector{Union{Missing, Float64}}}}, Pumas.ConstantCovar{NamedTuple{(:Cavg,), Tuple{Float64}}}, Vector{Pumas.Event{Float64, Float64, Float64, Float64, Float64, Float64, Int64}}, Vector{Float64}}, param::NamedTuple{(:θbaseline, :θPmax, :θTD, :θPOW, :θEmax, :θEC50, :θKt, :Ω_1, :σ_add), Tuple{Float64, Float64, Float64, Float64, Float64, Float64, Float64, PDMats.PDiagMat{Float64, Vector{Float64}}, Float64}}, vrandeffsorth::Vector{Float64}, approx::Pumas.FOCE, diffeq_options::NamedTuple{(), Tuple{}})
    @ Pumas /builds/PumasAI/PumasSystemImages-jl/.julia/packages/Pumas/HDuXQ/src/estimation/likelihoods.jl:1681
  [6] (::Pumas.var"#_fgh!#337"{PumasModel{ParamSet{NamedTuple{(:θbaseline, :θPmax, :θTD, :θPOW, :θEmax, :θEC50, :θKt, :Ω_1, :σ_add), Tuple{RealDomain{TransformVariables.Infinity{false}, TransformVariables.Infinity{true}, Float64}, RealDomain{TransformVariables.Infinity{false}, TransformVariables.Infinity{true}, Float64}, RealDomain{TransformVariables.Infinity{false}, TransformVariables.Infinity{true}, Float64}, RealDomain{TransformVariables.Infinity{false}, TransformVariables.Infinity{true}, Float64}, RealDomain{TransformVariables.Infinity{false}, TransformVariables.Infinity{true}, Float64}, RealDomain{TransformVariables.Infinity{false}, TransformVariables.Infinity{true}, Float64}, RealDomain{TransformVariables.Infinity{false}, TransformVariables.Infinity{true}, Float64}, PDiagDomain{PDMats.PDiagMat{Float64, Vector{Float64}}}, RealDomain{TransformVariables.Infinity{false}, TransformVariables.Infinity{true}, Float64}}}}, var"#877#901", var"#878#902", var"#880#904", var"#882#906", Nothing, var"#883#907", var"#892#916", Nothing}, Subject{NamedTuple{(:Observed,), Tuple{Vector{Union{Missing, Float64}}}}, Pumas.ConstantCovar{NamedTuple{(:Cavg,), Tuple{Float64}}}, Vector{Pumas.Event{Float64, Float64, Float64, Float64, Float64, Float64, Int64}}, Vector{Float64}}, NamedTuple{(:θbaseline, :θPmax, :θTD, :θPOW, :θEmax, :θEC50, :θKt, :Ω_1, :σ_add), Tuple{Float64, Float64, Float64, Float64, Float64, Float64, Float64, PDMats.PDiagMat{Float64, Vector{Float64}}, Float64}}, Pumas.FOCE, NamedTuple{(), Tuple{}}, TransformVariables.TransformTuple{NamedTuple{(:η_1,), Tuple{Pumas.MvNormalTransform{ZeroMeanDiagNormal{Tuple{Base.OneTo{Int64}}}}}}}, ParamSet{NamedTuple{(:η_1,), Tuple{ZeroMeanDiagNormal{Tuple{Base.OneTo{Int64}}}}}}})(F::Float64, G::Vector{Float64}, H::Matrix{Float64}, x::Vector{Float64})
    @ Pumas /builds/PumasAI/PumasSystemImages-jl/.julia/packages/Pumas/HDuXQ/src/estimation/likelihoods.jl:463
  [7] (::NLSolversBase.var"#98#104"{NLSolversBase.InplaceObjective{Nothing, Nothing, Pumas.var"#_fgh!#337"{PumasModel{ParamSet{NamedTuple{(:θbaseline, :θPmax, :θTD, :θPOW, :θEmax, :θEC50, :θKt, :Ω_1, :σ_add), Tuple{RealDomain{TransformVariables.Infinity{false}, TransformVariables.Infinity{true}, Float64}, RealDomain{TransformVariables.Infinity{false}, TransformVariables.Infinity{true}, Float64}, RealDomain{TransformVariables.Infinity{false}, TransformVariables.Infinity{true}, Float64}, RealDomain{TransformVariables.Infinity{false}, TransformVariables.Infinity{true}, Float64}, RealDomain{TransformVariables.Infinity{false}, TransformVariables.Infinity{true}, Float64}, RealDomain{TransformVariables.Infinity{false}, TransformVariables.Infinity{true}, Float64}, RealDomain{TransformVariables.Infinity{false}, TransformVariables.Infinity{true}, Float64}, PDiagDomain{PDMats.PDiagMat{Float64, Vector{Float64}}}, RealDomain{TransformVariables.Infinity{false}, TransformVariables.Infinity{true}, Float64}}}}, var"#877#901", var"#878#902", var"#880#904", var"#882#906", Nothing, var"#883#907", var"#892#916", Nothing}, Subject{NamedTuple{(:Observed,), Tuple{Vector{Union{Missing, Float64}}}}, Pumas.ConstantCovar{NamedTuple{(:Cavg,), Tuple{Float64}}}, Vector{Pumas.Event{Float64, Float64, Float64, Float64, Float64, Float64, Int64}}, Vector{Float64}}, NamedTuple{(:θbaseline, :θPmax, :θTD, :θPOW, :θEmax, :θEC50, :θKt, :Ω_1, :σ_add), Tuple{Float64, Float64, Float64, Float64, Float64, Float64, Float64, PDMats.PDiagMat{Float64, Vector{Float64}}, Float64}}, Pumas.FOCE, NamedTuple{(), Tuple{}}, TransformVariables.TransformTuple{NamedTuple{(:η_1,), Tuple{Pumas.MvNormalTransform{ZeroMeanDiagNormal{Tuple{Base.OneTo{Int64}}}}}}}, ParamSet{NamedTuple{(:η_1,), Tuple{ZeroMeanDiagNormal{Tuple{Base.OneTo{Int64}}}}}}}, Nothing, Nothing}, Float64})(G::Vector{Float64}, H::Matrix{Float64}, x::Vector{Float64})
    @ NLSolversBase /builds/PumasAI/PumasSystemImages-jl/.julia/packages/NLSolversBase/geyh3/src/objective_types/incomplete.jl:115
  [8] value_gradient_hessian!!(obj::NLSolversBase.TwiceDifferentiable{Float64, Vector{Float64}, Matrix{Float64}, Vector{Float64}}, x::Vector{Float64})
    @ NLSolversBase /builds/PumasAI/PumasSystemImages-jl/.julia/packages/NLSolversBase/geyh3/src/objective_types/incomplete.jl:138
  [9] initial_state(method::Optim.NewtonTrustRegion{Float64}, options::Optim.Options{Float64, Nothing}, d::NLSolversBase.TwiceDifferentiable{Float64, Vector{Float64}, Matrix{Float64}, Vector{Float64}}, initial_x::Vector{Float64})
    @ Optim /builds/PumasAI/PumasSystemImages-jl/.julia/packages/Optim/uwNqi/src/multivariate/solvers/second_order/newton_trust_region.jl:306
 [10] optimize
    @ /builds/PumasAI/PumasSystemImages-jl/.julia/packages/Optim/uwNqi/src/multivariate/optimize/optimize.jl:35 [inlined]
 [11] _orth_empirical_bayes!(vrandeffsorth::Vector{Float64}, m::PumasModel{ParamSet{NamedTuple{(:θbaseline, :θPmax, :θTD, :θPOW, :θEmax, :θEC50, :θKt, :Ω_1, :σ_add), Tuple{RealDomain{TransformVariables.Infinity{false}, TransformVariables.Infinity{true}, Float64}, RealDomain{TransformVariables.Infinity{false}, TransformVariables.Infinity{true}, Float64}, RealDomain{TransformVariables.Infinity{false}, TransformVariables.Infinity{true}, Float64}, RealDomain{TransformVariables.Infinity{false}, TransformVariables.Infinity{true}, Float64}, RealDomain{TransformVariables.Infinity{false}, TransformVariables.Infinity{true}, Float64}, RealDomain{TransformVariables.Infinity{false}, TransformVariables.Infinity{true}, Float64}, RealDomain{TransformVariables.Infinity{false}, TransformVariables.Infinity{true}, Float64}, PDiagDomain{PDMats.PDiagMat{Float64, Vector{Float64}}}, RealDomain{TransformVariables.Infinity{false}, TransformVariables.Infinity{true}, Float64}}}}, var"#877#901", var"#878#902", var"#880#904", var"#882#906", Nothing, var"#883#907", var"#892#916", Nothing}, subject::Subject{NamedTuple{(:Observed,), Tuple{Vector{Union{Missing, Float64}}}}, Pumas.ConstantCovar{NamedTuple{(:Cavg,), Tuple{Float64}}}, Vector{Pumas.Event{Float64, Float64, Float64, Float64, Float64, Float64, Int64}}, Vector{Float64}}, param::NamedTuple{(:θbaseline, :θPmax, :θTD, :θPOW, :θEmax, :θEC50, :θKt, :Ω_1, :σ_add), Tuple{Float64, Float64, Float64, Float64, Float64, Float64, Float64, PDMats.PDiagMat{Float64, Vector{Float64}}, Float64}}, approx::Pumas.FOCE, diffeq_options::NamedTuple{(), Tuple{}})
    @ Pumas /builds/PumasAI/PumasSystemImages-jl/.julia/packages/Pumas/HDuXQ/src/estimation/likelihoods.jl:487
 [12] _update_ebes_and_evaluate_marginal_nll!
    @ /builds/PumasAI/PumasSystemImages-jl/.julia/packages/Pumas/HDuXQ/src/estimation/likelihoods.jl:2054 [inlined]
 [13] _update_ebes_and_evaluate_marginal_nll_threads!(m::PumasModel{ParamSet{NamedTuple{(:θbaseline, :θPmax, :θTD, :θPOW, :θEmax, :θEC50, :θKt, :Ω_1, :σ_add), Tuple{RealDomain{TransformVariables.Infinity{false}, TransformVariables.Infinity{true}, Float64}, RealDomain{TransformVariables.Infinity{false}, TransformVariables.Infinity{true}, Float64}, RealDomain{TransformVariables.Infinity{false}, TransformVariables.Infinity{true}, Float64}, RealDomain{TransformVariables.Infinity{false}, TransformVariables.Infinity{true}, Float64}, RealDomain{TransformVariables.Infinity{false}, TransformVariables.Infinity{true}, Float64}, RealDomain{TransformVariables.Infinity{false}, TransformVariables.Infinity{true}, Float64}, RealDomain{TransformVariables.Infinity{false}, TransformVariables.Infinity{true}, Float64}, PDiagDomain{PDMats.PDiagMat{Float64, Vector{Float64}}}, RealDomain{TransformVariables.Infinity{false}, TransformVariables.Infinity{true}, Float64}}}}, var"#877#901", var"#878#902", var"#880#904", var"#882#906", Nothing, var"#883#907", var"#892#916", Nothing}, population::Vector{Subject{NamedTuple{(:Observed,), Tuple{Vector{Union{Missing, Float64}}}}, Pumas.ConstantCovar{NamedTuple{(:Cavg,), Tuple{Float64}}}, Vector{Pumas.Event{Float64, Float64, Float64, Float64, Float64, Float64, Int64}}, Vector{Float64}}}, param::NamedTuple{(:θbaseline, :θPmax, :θTD, :θPOW, :θEmax, :θEC50, :θKt, :Ω_1, :σ_add), Tuple{Float64, Float64, Float64, Float64, Float64, Float64, Float64, PDMats.PDiagMat{Float64, Vector{Float64}}, Float64}}, vvrandeffs::Vector{Vector{Float64}}, vvrandeffs_tmp::Vector{Vector{Float64}}, approx::Pumas.FOCE, diffeq_options::NamedTuple{(), Tuple{}})
    @ Pumas /builds/PumasAI/PumasSystemImages-jl/.julia/packages/Pumas/HDuXQ/src/estimation/likelihoods.jl:2109
 [14] #440
    @ /builds/PumasAI/PumasSystemImages-jl/.julia/packages/Pumas/HDuXQ/src/estimation/likelihoods.jl:2497 [inlined]
 [15] (::NLSolversBase.var"#69#70"{NLSolversBase.InplaceObjective{Nothing, Pumas.var"#440#445"{PumasModel{ParamSet{NamedTuple{(:θbaseline, :θPmax, :θTD, :θPOW, :θEmax, :θEC50, :θKt, :Ω_1, :σ_add), Tuple{RealDomain{TransformVariables.Infinity{false}, TransformVariables.Infinity{true}, Float64}, RealDomain{TransformVariables.Infinity{false}, TransformVariables.Infinity{true}, Float64}, RealDomain{TransformVariables.Infinity{false}, TransformVariables.Infinity{true}, Float64}, RealDomain{TransformVariables.Infinity{false}, TransformVariables.Infinity{true}, Float64}, RealDomain{TransformVariables.Infinity{false}, TransformVariables.Infinity{true}, Float64}, RealDomain{TransformVariables.Infinity{false}, TransformVariables.Infinity{true}, Float64}, RealDomain{TransformVariables.Infinity{false}, TransformVariables.Infinity{true}, Float64}, PDiagDomain{PDMats.PDiagMat{Float64, Vector{Float64}}}, RealDomain{TransformVariables.Infinity{false}, TransformVariables.Infinity{true}, Float64}}}}, var"#877#901", var"#878#902", var"#880#904", var"#882#906", Nothing, var"#883#907", var"#892#916", Nothing}, Vector{Subject{NamedTuple{(:Observed,), Tuple{Vector{Union{Missing, Float64}}}}, Pumas.ConstantCovar{NamedTuple{(:Cavg,), Tuple{Float64}}}, Vector{Pumas.Event{Float64, Float64, Float64, Float64, Float64, Float64, Int64}}, Vector{Float64}}}, Pumas.FOCE, EnsembleThreads, NamedTuple{(), Tuple{}}, TransformVariables.TransformTuple{NamedTuple{(:θbaseline, :θPmax, :θTD, :θPOW, :θEmax, :θEC50, :θKt, :Ω_1, :σ_add), Tuple{TransformVariables.Identity, TransformVariables.Identity, TransformVariables.Identity, TransformVariables.Identity, TransformVariables.Identity, TransformVariables.Identity, TransformVariables.Identity, Pumas.PDiagTransform, TransformVariables.Identity}}}, Vector{Vector{Float64}}, Vector{Vector{Float64}}}, Nothing, Nothing, Nothing}, Float64})(G::Vector{Float64}, x::Vector{Float64})
    @ NLSolversBase /builds/PumasAI/PumasSystemImages-jl/.julia/packages/NLSolversBase/geyh3/src/objective_types/incomplete.jl:54
 [16] value_gradient!!(obj::NLSolversBase.OnceDifferentiable{Float64, Vector{Float64}, Vector{Float64}}, x::Vector{Float64})
    @ NLSolversBase /builds/PumasAI/PumasSystemImages-jl/.julia/packages/NLSolversBase/geyh3/src/interface.jl:82
 [17] initial_state(method::Optim.BFGS{LineSearches.InitialStatic{Float64}, LineSearches.BackTracking{Float64, Int64}, Nothing, Float64, Optim.Flat}, options::Optim.Options{Float64, Pumas.var"#425#427"{Pumas.DefaultOptimizeFN{Nothing, NamedTuple{(:show_trace, :store_trace, :extended_trace, :g_tol, :allow_f_increases), Tuple{Bool, Bool, Bool, Float64, Bool}}}, Pumas.var"#441#446"{Pumas.FOCE, Bool, NLSolversBase.OnceDifferentiable{Float64, Vector{Float64}, Vector{Float64}}, TransformVariables.TransformTuple{NamedTuple{(:θbaseline, :θPmax, :θTD, :θPOW, :θEmax, :θEC50, :θKt, :Ω_1, :σ_add), Tuple{TransformVariables.Identity, TransformVariables.Identity, TransformVariables.Identity, TransformVariables.Identity, TransformVariables.Identity, TransformVariables.Identity, TransformVariables.Identity, Pumas.PDiagTransform, TransformVariables.Identity}}}}}}, d::NLSolversBase.OnceDifferentiable{Float64, Vector{Float64}, Vector{Float64}}, initial_x::Vector{Float64})
    @ Optim /builds/PumasAI/PumasSystemImages-jl/.julia/packages/Optim/uwNqi/src/multivariate/solvers/first_order/bfgs.jl:85
 [18] optimize
    @ /builds/PumasAI/PumasSystemImages-jl/.julia/packages/Optim/uwNqi/src/multivariate/optimize/optimize.jl:35 [inlined]
 [19] DefaultOptimizeFN
    @ /builds/PumasAI/PumasSystemImages-jl/.julia/packages/Pumas/HDuXQ/src/estimation/likelihoods.jl:1973 [inlined]
 [20] _fit(m::PumasModel{ParamSet{NamedTuple{(:θbaseline, :θPmax, :θTD, :θPOW, :θEmax, :θEC50, :θKt, :Ω_1, :σ_add), Tuple{RealDomain{TransformVariables.Infinity{false}, TransformVariables.Infinity{true}, Float64}, RealDomain{TransformVariables.Infinity{false}, TransformVariables.Infinity{true}, Float64}, RealDomain{TransformVariables.Infinity{false}, TransformVariables.Infinity{true}, Float64}, RealDomain{TransformVariables.Infinity{false}, TransformVariables.Infinity{true}, Float64}, RealDomain{TransformVariables.Infinity{false}, TransformVariables.Infinity{true}, Float64}, RealDomain{TransformVariables.Infinity{false}, TransformVariables.Infinity{true}, Float64}, RealDomain{TransformVariables.Infinity{false}, TransformVariables.Infinity{true}, Float64}, PDiagDomain{PDMats.PDiagMat{Float64, Vector{Float64}}}, RealDomain{TransformVariables.Infinity{false}, TransformVariables.Infinity{true}, Float64}}}}, var"#877#901", var"#878#902", var"#880#904", var"#882#906", Nothing, var"#883#907", var"#892#916", Nothing}, population::Vector{Subject{NamedTuple{(:Observed,), Tuple{Vector{Union{Missing, Float64}}}}, Pumas.ConstantCovar{NamedTuple{(:Cavg,), Tuple{Float64}}}, Vector{Pumas.Event{Float64, Float64, Float64, Float64, Float64, Float64, Int64}}, Vector{Float64}}}, param::NamedTuple{(:θbaseline, :θPmax, :θTD, :θPOW, :θEmax, :θEC50, :θKt, :Ω_1, :σ_add), Tuple{Float64, Float64, Float64, Float64, Float64, Float64, Float64, Diagonal{Float64, Vector{Float64}}, Float64}}, approx::Pumas.FOCE, ensemblealg::EnsembleThreads, optimize_fn::Pumas.DefaultOptimizeFN{Nothing, NamedTuple{(:show_trace, :store_trace, :extended_trace, :g_tol, :allow_f_increases), Tuple{Bool, Bool, Bool, Float64, Bool}}}, fixedparamset::ParamSet{NamedTuple{(:θbaseline, :θPmax, :θTD, :θPOW, :θEmax, :θEC50, :θKt, :Ω_1, :σ_add), Tuple{RealDomain{TransformVariables.Infinity{false}, TransformVariables.Infinity{true}, Float64}, RealDomain{TransformVariables.Infinity{false}, TransformVariables.Infinity{true}, Float64}, RealDomain{TransformVariables.Infinity{false}, TransformVariables.Infinity{true}, Float64}, RealDomain{TransformVariables.Infinity{false}, TransformVariables.Infinity{true}, Float64}, RealDomain{TransformVariables.Infinity{false}, TransformVariables.Infinity{true}, Float64}, RealDomain{TransformVariables.Infinity{false}, TransformVariables.Infinity{true}, Float64}, RealDomain{TransformVariables.Infinity{false}, TransformVariables.Infinity{true}, Float64}, PDiagDomain{PDMats.PDiagMat{Float64, Vector{Float64}}}, RealDomain{TransformVariables.Infinity{false}, TransformVariables.Infinity{true}, Float64}}}}, fixedparam::NamedTuple{(:θbaseline, :θPmax, :θTD, :θPOW, :θEmax, :θEC50, :θKt, :Ω_1, :σ_add), Tuple{Float64, Float64, Float64, Float64, Float64, Float64, Float64, Diagonal{Float64, Vector{Float64}}, Float64}}, checkidentification::Bool, diffeq_options::NamedTuple{(), Tuple{}})
    @ Pumas /builds/PumasAI/PumasSystemImages-jl/.julia/packages/Pumas/HDuXQ/src/estimation/likelihoods.jl:2548
 [21] fit(m::PumasModel{ParamSet{NamedTuple{(:θbaseline, :θPmax, :θTD, :θPOW, :θEmax, :θEC50, :θKt, :Ω_1, :σ_add), Tuple{RealDomain{TransformVariables.Infinity{false}, TransformVariables.Infinity{true}, Float64}, RealDomain{TransformVariables.Infinity{false}, TransformVariables.Infinity{true}, Float64}, RealDomain{TransformVariables.Infinity{false}, TransformVariables.Infinity{true}, Float64}, RealDomain{TransformVariables.Infinity{false}, TransformVariables.Infinity{true}, Float64}, RealDomain{TransformVariables.Infinity{false}, TransformVariables.Infinity{true}, Float64}, RealDomain{TransformVariables.Infinity{false}, TransformVariables.Infinity{true}, Float64},

Any idea what is the interpretation of the error?
Thanks

2

Hi Ahmed, few suggestions:

  1. The error says there is some issue in trying to perform a multiplication. I realized that in your @derived block the broadcasting is not written for all operations. May be change the code to one of the following two:
    • PANSS = baseline .* (1 .- (Placebo)) .* (1 .- (Drug .*Delay)) (notice the .* between Drug and Delay that wasn’t there in your code
    • PANSS = @. baseline * (1 - Placebo) * (1 - Drug*Delay)
  2. You might also want to look into the first equation in @vars. Similar to above, it should be modified to:
    • Placebo = @. Pmax * (1- exp( -(t/TD) )^POW)
    • Placebo = (Pmax*(1 .- exp(.-(t ./TD)) .^POW))
  3. When fitting you might want to put lower bounds =0 when defining the model in the @param block, as not constraining can lead to untoward results that are not meaningful
  4. You defined choose_covariates_2() function in the code but you ran choose_covariates_1() in your simulations. I am assuming both are similar. Make sure to use the right one when performing simulations.
1 Like
3

Hi Rahul,
Thanks for the suggestions. I adjusted the code and the fit function does not show the error.

1 Like