Introduction to Pumas
This is an introduction to Pumas, a software for pharmaceutical modeling and simulation.
The basic workflow of Pumas is:
- Build a model.
- Define subjects or populations to simulate or estimate.
- Analyze the results with post-processing and plots.
We will show how to build a multiple-response PK/PD model via the @model
macro, define a subject with single doses, and analyze the results of the simulation. Fitting of data using any of the methods available in Pumas is showcased in the tutorials. This tutorial is designed as a broad overview of the workflow and a more in-depth treatment of each section can be found in the tutorials.
Working Example
Let's start by showing a complete simulation code, and then break down how it works.
using StableRNGs
using Pumas
using PumasUtilities
using CairoMakie
######### Turnover model
inf_2cmt_lin_turnover = @model begin
@param begin
tvcl ∈ RealDomain(lower = 0)
tvvc ∈ RealDomain(lower = 0)
tvq ∈ RealDomain(lower = 0)
tvvp ∈ RealDomain(lower = 0)
Ω_pk ∈ PDiagDomain(4)
σ_prop_pk ∈ RealDomain(lower = 0)
σ_add_pk ∈ RealDomain(lower = 0)
# PD parameters
tvturn ∈ RealDomain(lower = 0)
tvebase ∈ RealDomain(lower = 0)
tvec50 ∈ RealDomain(lower = 0)
Ω_pd ∈ PDiagDomain(1)
σ_add_pd ∈ RealDomain(lower = 0)
end
@random begin
ηpk ~ MvNormal(Ω_pk)
ηpd ~ MvNormal(Ω_pd)
end
@pre begin
CL = tvcl * exp(ηpk[1])
Vc = tvvc * exp(ηpk[2])
Q = tvq * exp(ηpk[3])
Vp = tvvp * exp(ηpk[4])
ebase = tvebase * exp(ηpd[1])
ec50 = tvec50
emax = 1
turn = tvturn
kout = 1 / turn
kin0 = ebase * kout
end
@init begin
Resp = ebase
end
@vars begin
conc := Central / Vc
edrug := emax * conc / (ec50 + conc)
kin := kin0 * (1 - edrug)
end
@dynamics begin
Central' = -(CL / Vc) * Central + (Q / Vp) * Peripheral - (Q / Vc) * Central
Peripheral' = (Q / Vc) * Central - (Q / Vp) * Peripheral
Resp' = kin - kout * Resp
end
@derived begin
dv ~ @. Normal(conc, sqrt((conc * σ_prop_pk)^2 + σ_add_pk^2))
resp ~ @. Normal(Resp, σ_add_pd)
end
end
turnover_params = (
tvcl = 1.5,
tvvc = 25.0,
tvq = 5.0,
tvvp = 150.0,
tvturn = 10,
tvebase = 10,
tvec50 = 0.3,
Ω_pk = Diagonal([0.05, 0.05, 0.05, 0.05]),
Ω_pd = Diagonal([0.05]),
σ_prop_pk = 0.15,
σ_add_pk = 0.5,
σ_add_pd = 0.2,
)
(tvcl = 1.5,
tvvc = 25.0,
tvq = 5.0,
tvvp = 150.0,
tvturn = 10,
tvebase = 10,
tvec50 = 0.3,
Ω_pk = [0.05 0.0 0.0 0.0; 0.0 0.05 0.0 0.0; 0.0 0.0 0.05 0.0; 0.0 0.0 0.0 0.05],
Ω_pd = [0.05;;],
σ_prop_pk = 0.15,
σ_add_pk = 0.5,
σ_add_pd = 0.2,)
regimen = DosageRegimen(150, rate = 10, cmt = :Central)
pop = map(i -> Subject(id = i,events = regimen), 1:10)
Population
Subjects: 10
Observations:
sd_obstimes = [0.25, 0.5, 0.75, 1, 2, 4, 8,
12, 16, 20, 24, 36, 48, 60, 71.9] # single dose observation times
15-element Vector{Float64}:
0.25
0.5
0.75
1.0
2.0
4.0
8.0
12.0
16.0
20.0
24.0
36.0
48.0
60.0
71.9
sims = simobs(
inf_2cmt_lin_turnover,
pop,
turnover_params,
obstimes = sd_obstimes,
rng = StableRNG(123),
)
Simulated population (Vector{<:Subject})
Simulated subjects: 10
Simulated variables: dv, resp
sim_plot(
inf_2cmt_lin_turnover,
sims, observations =[:dv],
figure = (fontsize = 18, ),
axis = (
xlabel = "Time (hr)",
ylabel = "Concentration (ng/mL)",
)
)
sim_plot(
inf_2cmt_lin_turnover,
sims, observations =[:resp],
figure = (fontsize = 18, ),
axis = (
xlabel = "Time (hr)",
ylabel = "Response",
)
)
In this code, we defined a nonlinear mixed effects model by describing the parameters, the random effects, the dynamical model, and the derived (result) values. Then we generated a population of 10 subjects who received a single dose of 150mg, specified parameter values, simulated the model, and generated a plot of the results. Now let's walk through this process!
Using the Model Macro
First we define the model. The simplest way to do is via @model
. Inside of the @model
block we have a few subsections. The first of these is a @param
block. In here we define what kind of parameters we have. For this model we will define structural model parameters of PK and PD and their corresponding variances where applicable:
@param begin
tvcl ∈ RealDomain(lower = 0)
tvvc ∈ RealDomain(lower = 0)
tvq ∈ RealDomain(lower = 0)
tvvp ∈ RealDomain(lower = 0)
Ω_pk ∈ PDiagDomain(4)
σ_prop_pk ∈ RealDomain(lower = 0)
σ_add_pk ∈ RealDomain(lower = 0)
# PD parameters
tvturn ∈ RealDomain(lower = 0)
tvebase ∈ RealDomain(lower = 0)
tvec50 ∈ RealDomain(lower = 0)
Ω_pd ∈ PDiagDomain(1)
σ_add_pd ∈ RealDomain(lower = 0)
end
Next we define our random effects. The random effects are defined by a distribution from the Distributions.jl package. For more information on defining distributions, please see the Distributions.jl documentation. For this tutorial, we wish to have a multivariate normal of uncorrelated random effects, one for PK and another for PD so we utilize the syntax:
@random begin
ηpk ~ MvNormal(Ω_pk)
ηpd ~ MvNormal(Ω_pd)
end
Now we define our pre-processing step in @pre
. This is where we choose how the parameters, random effects, and the covariates collate. We define the values and give them a name as follows:
@pre begin
CL = tvcl * exp(ηpk[1])
Vc = tvvc * exp(ηpk[2])
Q = tvq * exp(ηpk[3])
Vp = tvvp * exp(ηpk[4])
ebase = tvebase * exp(ηpd[1])
ec50 = tvec50
emax = 1
turn = tvturn
kout = 1 / turn
kin0 = ebase * kout
end
Next we define the @init
block which gives the initial values for our differential equations. Any variable not mentioned in this block is assumed to have a zero for its starting value. We wish to only set the starting value for Resp
, and thus we use:
@init begin
Resp = ebase
end
Now we define our dynamics. We do this via the @dynamics
block. Differential variables are declared by having a line defining their derivative. For our model, we use:
@dynamics begin
Central' = -(CL / Vc) * Central + (Q / Vp) * Peripheral - (Q / Vc) * Central
Peripheral' = (Q / Vc) * Central - (Q / Vp) * Peripheral
Resp' = kin - kout * Resp
end
Next we setup alias variables that can be used later in the code. Such alias code can be setup in the @vars
block:
@vars begin
conc := Central / Vc
edrug := emax * conc / (ec50 + conc)
kin := kin0 * (1 - edrug)
end
Lastly we utilize the @derived
macro to define our post-processing. We can output values using the following:
@derived begin
dv ~ @. Normal(conc, sqrt((conc * σ_prop_pk)^2 + σ_add_pk^2))
resp ~ @. Normal(Resp, σ_add_pd)
end
Building a Subject
Now let's build a subject to simulate the model with. A subject is defined by the following components:
- An identifier -
id
- The dosage regimen -
events
- The covariates of the individual -
covariates
- Observations associated with the individual -
observations
- The timing of the sampling -
time
- A vector of times if the covariates are time-varying -
covariate_time
- Interpolation direction for covariates -
covariate_direction
Our model did not make use of covariates so we will ignore covariate components 3, 6 and 7 for now, and observations (4) are only necessary for fitting parameters to data which will not be covered in this tutorial. Thus our subject will be defined simply by its dosage regimen.
To do this, we use the DosageRegimen
constructor. The first value is always the dosing amount. Optionally, additional arguments can be specified. The most important one is time
which specifies the time that the dosing occurs. For example,
DosageRegimen(150, time=0)
is a dosage regimen with a single dose of amount 150 at time t=0
. Let's assume the dose is an infusion administered at the rate of 10 mg/hour into the first compartment:
regimen = DosageRegimen(150, rate=10, cmt=1)
1 rows × 10 columns
time | cmt | amt | evid | ii | addl | rate | duration | ss | route | |
---|---|---|---|---|---|---|---|---|---|---|
Float64 | Int64 | Float64 | Int8 | Float64 | Int64 | Float64 | Float64 | Int8 | NCA.Route | |
1 | 0.0 | 1 | 150.0 | 1 | 0.0 | 0 | 10.0 | 15.0 | 0 | NullRoute |
Let's define our subject to have id=1
and this multiple dosing regimen:
subject = Subject(id = 1, events = regimen)
Subject
ID: 1
Events: 2
You can also create a collection of subjects as a Population
.
pop = Population(map(i -> Subject(id= i, events = regimen), 1:10))
Population
Subjects: 10
Observations:
Running a Simulation
The main function for running a simulation is simobs
. simobs
on a Population
simulates all subjects of the population, while simobs
on a Subject
simulates just that subject. If we wish to change the parameters from the initialized values, then we pass them in. Let's simulate subject 1 with a set of chosen parameters:
turnover_params = (
tvcl = 1.5,
tvvc = 25.0,
tvq = 5.0,
tvvp = 150.0,
tvturn = 10,
tvebase = 10,
tvec50 = 0.3,
Ω_pk = Diagonal([0.05, 0.05, 0.05, 0.05]),
Ω_pd = Diagonal([0.05]),
σ_prop_pk = 0.15,
σ_add_pk = 0.5,
σ_add_pd = 0.2
)
sims = simobs(
inf_2cmt_lin_turnover,
pop,
turnover_params,
obstimes = sd_obstimes,
rng = StableRNG(123),
)
Simulated population (Vector{<:Subject})
Simulated subjects: 10
Simulated variables: dv, resp
We can then plot the simulated observations by using the sim_plot
command:
sim_plot(inf_2cmt_lin_turnover, sims, observations = :dv)
Note that we can further modify the plot, see Customizing Plots. For example,
sim_plot(
inf_2cmt_lin_turnover,
sims, observations =[:dv],
figure = (fontsize = 18,),
axis = (
xlabel = "Time (hr)",
ylabel = "Concentration (ng/mL)",
)
)
When we only give the parameters, the random effects are automatically sampled from their distributions. If we wish to prescribe a value for the random effects, we pass initial values similarly:
rng = StableRNG(123)
vrandeffs = [(ηpk = rand(rng, 4), ηpd = rand(rng, 1),) for _ in pop]
sims = simobs(
inf_2cmt_lin_turnover,
pop,
turnover_params,
vrandeffs,
obstimes = sd_obstimes,
rng = rng,
)
Simulated population (Vector{<:Subject})
Simulated subjects: 10
Simulated variables: dv, resp
If a population simulation is required with the random effects set to zero, then it is possible to use the zero_randeffs
function:
etas = zero_randeffs(
inf_2cmt_lin_turnover,
turnover_params,
pop
)
sims = simobs(
inf_2cmt_lin_turnover,
pop,
turnover_params,
etas;
obstimes = sd_obstimes,
rng = StableRNG(123),
)
fig = Figure(; resolution=(1000,600), fontsize = 18)
ax1 = Axis(
fig[1,1];
xlabel = "Time (hr)",
ylabel = "Concentration (ng/mL)",
)
ax2 = Axis(
fig[1,2];
xlabel = "Time (hr)",
ylabel = "Response",
)
sim_plot!(
ax1, inf_2cmt_lin_turnover,
sims, observations =[:dv],
)
sim_plot!(
ax2, inf_2cmt_lin_turnover,
sims, observations =[:resp],
)
fig
You still see variability in the plot above, mainly due to the residual variability components in the model. If we set the variance parameters to zero as below
turnover_params_wo_sigma = (turnover_params..., σ_prop_pk = 0.0, σ_add_pk = 0.0, σ_add_pd = 0.0)
(tvcl = 1.5,
tvvc = 25.0,
tvq = 5.0,
tvvp = 150.0,
tvturn = 10,
tvebase = 10,
tvec50 = 0.3,
Ω_pk = [0.05 0.0 0.0 0.0; 0.0 0.05 0.0 0.0; 0.0 0.0 0.05 0.0; 0.0 0.0 0.0 0.05],
Ω_pd = [0.05;;],
σ_prop_pk = 0.0,
σ_add_pk = 0.0,
σ_add_pd = 0.0,)
and perform the simulation without random effects again we get only the population mean:
etas = zero_randeffs(
inf_2cmt_lin_turnover,
turnover_params,
pop
)
sims = simobs(
inf_2cmt_lin_turnover,
pop,
turnover_params_wo_sigma,
etas;
obstimes = sd_obstimes,
rng = StableRNG(123),
)
fig = Figure(; resolution=(1000,600), fontsize = 18)
ax1 = Axis(
fig[1,1];
xlabel = "Time (hr)",
ylabel = "Concentration (ng/mL)",
)
ax2 = Axis(
fig[1,2];
xlabel = "Time (hr)",
ylabel = "Response",
)
sim_plot!(
ax1, inf_2cmt_lin_turnover,
sims, observations =[:dv],
)
sim_plot!(
ax2, inf_2cmt_lin_turnover,
sims, observations =[:resp],
)
fig
Handling the resulting SimulatedObservations
The resulting sims
object contains the results of the simulation for each subject. The results for the i
th subject can be retrieved by sims[i]
and are of type SimulatedObservations
. Each SimulatedObservations
has two fields: sims[i].time
is an array of time points for which the data was saved. sims[i].observations
is the result of the derived variables. From there, the derived variables are accessed by name. For example,
sims[1].observations[:dv]
is the array of dv
values at the associated time points for subject 1. We can convert the simulation results to Pumas Subject
s using the constructor broadcasted over all elements of sims
:
sims_subjects = Subject.(sims)
Population
Subjects: 10
Observations: dv, resp
Then sims_subjects
can be used to fit the model parameters based on the simulated dataset. We can also turn the simulated population into a DataFrame
with the DataFrame
constructor:
DataFrame(sims)
160 rows × 26 columns
id | time | dv | resp | evid | amt | cmt | rate | ηpk_1 | ηpk_2 | ηpk_3 | ηpk_4 | ηpd_1 | Central | Peripheral | Resp | CL | Vc | Q | Vp | ebase | ec50 | emax | turn | kout | kin0 | |
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
String? | Float64 | Float64? | Float64? | Int8? | Float64? | Symbol? | Float64? | Float64? | Float64? | Float64? | Float64? | Float64? | Float64? | Float64? | Float64? | Float64? | Float64? | Float64? | Float64? | Float64? | Float64? | Int64? | Int64? | Float64? | Float64? | |
1 | 1 | 0.0 | missing | missing | 1 | 150.0 | Central | 10.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | missing | missing | missing | 1.5 | 25.0 | 5.0 | 150.0 | 10.0 | 0.3 | 1 | 10 | 0.1 | 1.0 |
2 | 1 | 0.25 | 0.096826 | 9.96663 | 0 | missing | missing | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 2.42065 | 0.0609992 | 9.96663 | 1.5 | 25.0 | 5.0 | 150.0 | 10.0 | 0.3 | 1 | 10 | 0.1 | 1.0 |
3 | 1 | 0.5 | 0.187597 | 9.88839 | 0 | missing | missing | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 4.68993 | 0.238203 | 9.88839 | 1.5 | 25.0 | 5.0 | 150.0 | 10.0 | 0.3 | 1 | 10 | 0.1 | 1.0 |
4 | 1 | 0.75 | 0.272731 | 9.78409 | 0 | missing | missing | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 6.81828 | 0.523374 | 9.78409 | 1.5 | 25.0 | 5.0 | 150.0 | 10.0 | 0.3 | 1 | 10 | 0.1 | 1.0 |
5 | 1 | 1.0 | 0.352616 | 9.66347 | 0 | missing | missing | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 8.8154 | 0.908843 | 9.66347 | 1.5 | 25.0 | 5.0 | 150.0 | 10.0 | 0.3 | 1 | 10 | 0.1 | 1.0 |
6 | 1 | 2.0 | 0.626531 | 9.10546 | 0 | missing | missing | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 15.6633 | 3.31813 | 9.10546 | 1.5 | 25.0 | 5.0 | 150.0 | 10.0 | 0.3 | 1 | 10 | 0.1 | 1.0 |
7 | 1 | 4.0 | 1.01152 | 7.93649 | 0 | missing | missing | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 25.2881 | 11.1916 | 7.93649 | 1.5 | 25.0 | 5.0 | 150.0 | 10.0 | 0.3 | 1 | 10 | 0.1 | 1.0 |
8 | 1 | 8.0 | 1.43067 | 5.95748 | 0 | missing | missing | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 35.7668 | 33.2305 | 5.95748 | 1.5 | 25.0 | 5.0 | 150.0 | 10.0 | 0.3 | 1 | 10 | 0.1 | 1.0 |
9 | 1 | 12.0 | 1.65869 | 4.52562 | 0 | missing | missing | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 41.4673 | 58.211 | 4.52562 | 1.5 | 25.0 | 5.0 | 150.0 | 10.0 | 0.3 | 1 | 10 | 0.1 | 1.0 |
10 | 1 | 16.0 | 1.47042 | 3.52807 | 0 | missing | missing | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 36.7604 | 82.7287 | 3.52807 | 1.5 | 25.0 | 5.0 | 150.0 | 10.0 | 0.3 | 1 | 10 | 0.1 | 1.0 |
11 | 1 | 20.0 | 0.81701 | 3.10522 | 0 | missing | missing | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 20.4252 | 92.5612 | 3.10522 | 1.5 | 25.0 | 5.0 | 150.0 | 10.0 | 0.3 | 1 | 10 | 0.1 | 1.0 |
12 | 1 | 24.0 | 0.599389 | 3.09228 | 0 | missing | missing | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 14.9847 | 93.8667 | 3.09228 | 1.5 | 25.0 | 5.0 | 150.0 | 10.0 | 0.3 | 1 | 10 | 0.1 | 1.0 |
13 | 1 | 36.0 | 0.467029 | 3.55706 | 0 | missing | missing | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 11.6757 | 87.9834 | 3.55706 | 1.5 | 25.0 | 5.0 | 150.0 | 10.0 | 0.3 | 1 | 10 | 0.1 | 1.0 |
14 | 1 | 48.0 | 0.426772 | 3.89715 | 0 | missing | missing | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 10.6693 | 80.9633 | 3.89715 | 1.5 | 25.0 | 5.0 | 150.0 | 10.0 | 0.3 | 1 | 10 | 0.1 | 1.0 |
15 | 1 | 60.0 | 0.392367 | 4.14396 | 0 | missing | missing | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 9.80916 | 74.4559 | 4.14396 | 1.5 | 25.0 | 5.0 | 150.0 | 10.0 | 0.3 | 1 | 10 | 0.1 | 1.0 |
16 | 1 | 71.9 | 0.361073 | 4.36054 | 0 | missing | missing | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 9.02683 | 68.5177 | 4.36054 | 1.5 | 25.0 | 5.0 | 150.0 | 10.0 | 0.3 | 1 | 10 | 0.1 | 1.0 |
17 | 2 | 0.0 | missing | missing | 1 | 150.0 | Central | 10.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | missing | missing | missing | 1.5 | 25.0 | 5.0 | 150.0 | 10.0 | 0.3 | 1 | 10 | 0.1 | 1.0 |
18 | 2 | 0.25 | 0.096826 | 9.96663 | 0 | missing | missing | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 2.42065 | 0.0609992 | 9.96663 | 1.5 | 25.0 | 5.0 | 150.0 | 10.0 | 0.3 | 1 | 10 | 0.1 | 1.0 |
19 | 2 | 0.5 | 0.187597 | 9.88839 | 0 | missing | missing | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 4.68993 | 0.238203 | 9.88839 | 1.5 | 25.0 | 5.0 | 150.0 | 10.0 | 0.3 | 1 | 10 | 0.1 | 1.0 |
20 | 2 | 0.75 | 0.272731 | 9.78409 | 0 | missing | missing | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 6.81828 | 0.523374 | 9.78409 | 1.5 | 25.0 | 5.0 | 150.0 | 10.0 | 0.3 | 1 | 10 | 0.1 | 1.0 |
21 | 2 | 1.0 | 0.352616 | 9.66347 | 0 | missing | missing | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 8.8154 | 0.908843 | 9.66347 | 1.5 | 25.0 | 5.0 | 150.0 | 10.0 | 0.3 | 1 | 10 | 0.1 | 1.0 |
22 | 2 | 2.0 | 0.626531 | 9.10546 | 0 | missing | missing | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 15.6633 | 3.31813 | 9.10546 | 1.5 | 25.0 | 5.0 | 150.0 | 10.0 | 0.3 | 1 | 10 | 0.1 | 1.0 |
23 | 2 | 4.0 | 1.01152 | 7.93649 | 0 | missing | missing | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 25.2881 | 11.1916 | 7.93649 | 1.5 | 25.0 | 5.0 | 150.0 | 10.0 | 0.3 | 1 | 10 | 0.1 | 1.0 |
24 | 2 | 8.0 | 1.43067 | 5.95748 | 0 | missing | missing | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 35.7668 | 33.2305 | 5.95748 | 1.5 | 25.0 | 5.0 | 150.0 | 10.0 | 0.3 | 1 | 10 | 0.1 | 1.0 |
25 | 2 | 12.0 | 1.65869 | 4.52562 | 0 | missing | missing | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 41.4673 | 58.211 | 4.52562 | 1.5 | 25.0 | 5.0 | 150.0 | 10.0 | 0.3 | 1 | 10 | 0.1 | 1.0 |
26 | 2 | 16.0 | 1.47042 | 3.52807 | 0 | missing | missing | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 36.7604 | 82.7287 | 3.52807 | 1.5 | 25.0 | 5.0 | 150.0 | 10.0 | 0.3 | 1 | 10 | 0.1 | 1.0 |
27 | 2 | 20.0 | 0.81701 | 3.10522 | 0 | missing | missing | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 20.4252 | 92.5612 | 3.10522 | 1.5 | 25.0 | 5.0 | 150.0 | 10.0 | 0.3 | 1 | 10 | 0.1 | 1.0 |
28 | 2 | 24.0 | 0.599389 | 3.09228 | 0 | missing | missing | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 14.9847 | 93.8667 | 3.09228 | 1.5 | 25.0 | 5.0 | 150.0 | 10.0 | 0.3 | 1 | 10 | 0.1 | 1.0 |
29 | 2 | 36.0 | 0.467029 | 3.55706 | 0 | missing | missing | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 11.6757 | 87.9834 | 3.55706 | 1.5 | 25.0 | 5.0 | 150.0 | 10.0 | 0.3 | 1 | 10 | 0.1 | 1.0 |
30 | 2 | 48.0 | 0.426772 | 3.89715 | 0 | missing | missing | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 10.6693 | 80.9633 | 3.89715 | 1.5 | 25.0 | 5.0 | 150.0 | 10.0 | 0.3 | 1 | 10 | 0.1 | 1.0 |
31 | 2 | 60.0 | 0.392367 | 4.14396 | 0 | missing | missing | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 9.80916 | 74.4559 | 4.14396 | 1.5 | 25.0 | 5.0 | 150.0 | 10.0 | 0.3 | 1 | 10 | 0.1 | 1.0 |
32 | 2 | 71.9 | 0.361073 | 4.36054 | 0 | missing | missing | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 9.02683 | 68.5177 | 4.36054 | 1.5 | 25.0 | 5.0 | 150.0 | 10.0 | 0.3 | 1 | 10 | 0.1 | 1.0 |
33 | 3 | 0.0 | missing | missing | 1 | 150.0 | Central | 10.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | missing | missing | missing | 1.5 | 25.0 | 5.0 | 150.0 | 10.0 | 0.3 | 1 | 10 | 0.1 | 1.0 |
34 | 3 | 0.25 | 0.096826 | 9.96663 | 0 | missing | missing | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 2.42065 | 0.0609992 | 9.96663 | 1.5 | 25.0 | 5.0 | 150.0 | 10.0 | 0.3 | 1 | 10 | 0.1 | 1.0 |
35 | 3 | 0.5 | 0.187597 | 9.88839 | 0 | missing | missing | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 4.68993 | 0.238203 | 9.88839 | 1.5 | 25.0 | 5.0 | 150.0 | 10.0 | 0.3 | 1 | 10 | 0.1 | 1.0 |
36 | 3 | 0.75 | 0.272731 | 9.78409 | 0 | missing | missing | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 6.81828 | 0.523374 | 9.78409 | 1.5 | 25.0 | 5.0 | 150.0 | 10.0 | 0.3 | 1 | 10 | 0.1 | 1.0 |
37 | 3 | 1.0 | 0.352616 | 9.66347 | 0 | missing | missing | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 8.8154 | 0.908843 | 9.66347 | 1.5 | 25.0 | 5.0 | 150.0 | 10.0 | 0.3 | 1 | 10 | 0.1 | 1.0 |
38 | 3 | 2.0 | 0.626531 | 9.10546 | 0 | missing | missing | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 15.6633 | 3.31813 | 9.10546 | 1.5 | 25.0 | 5.0 | 150.0 | 10.0 | 0.3 | 1 | 10 | 0.1 | 1.0 |
39 | 3 | 4.0 | 1.01152 | 7.93649 | 0 | missing | missing | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 25.2881 | 11.1916 | 7.93649 | 1.5 | 25.0 | 5.0 | 150.0 | 10.0 | 0.3 | 1 | 10 | 0.1 | 1.0 |
40 | 3 | 8.0 | 1.43067 | 5.95748 | 0 | missing | missing | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 35.7668 | 33.2305 | 5.95748 | 1.5 | 25.0 | 5.0 | 150.0 | 10.0 | 0.3 | 1 | 10 | 0.1 | 1.0 |
41 | 3 | 12.0 | 1.65869 | 4.52562 | 0 | missing | missing | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 41.4673 | 58.211 | 4.52562 | 1.5 | 25.0 | 5.0 | 150.0 | 10.0 | 0.3 | 1 | 10 | 0.1 | 1.0 |
42 | 3 | 16.0 | 1.47042 | 3.52807 | 0 | missing | missing | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 36.7604 | 82.7287 | 3.52807 | 1.5 | 25.0 | 5.0 | 150.0 | 10.0 | 0.3 | 1 | 10 | 0.1 | 1.0 |
43 | 3 | 20.0 | 0.81701 | 3.10522 | 0 | missing | missing | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 20.4252 | 92.5612 | 3.10522 | 1.5 | 25.0 | 5.0 | 150.0 | 10.0 | 0.3 | 1 | 10 | 0.1 | 1.0 |
44 | 3 | 24.0 | 0.599389 | 3.09228 | 0 | missing | missing | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 14.9847 | 93.8667 | 3.09228 | 1.5 | 25.0 | 5.0 | 150.0 | 10.0 | 0.3 | 1 | 10 | 0.1 | 1.0 |
45 | 3 | 36.0 | 0.467029 | 3.55706 | 0 | missing | missing | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 11.6757 | 87.9834 | 3.55706 | 1.5 | 25.0 | 5.0 | 150.0 | 10.0 | 0.3 | 1 | 10 | 0.1 | 1.0 |
46 | 3 | 48.0 | 0.426772 | 3.89715 | 0 | missing | missing | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 10.6693 | 80.9633 | 3.89715 | 1.5 | 25.0 | 5.0 | 150.0 | 10.0 | 0.3 | 1 | 10 | 0.1 | 1.0 |
47 | 3 | 60.0 | 0.392367 | 4.14396 | 0 | missing | missing | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 9.80916 | 74.4559 | 4.14396 | 1.5 | 25.0 | 5.0 | 150.0 | 10.0 | 0.3 | 1 | 10 | 0.1 | 1.0 |
48 | 3 | 71.9 | 0.361073 | 4.36054 | 0 | missing | missing | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 9.02683 | 68.5177 | 4.36054 | 1.5 | 25.0 | 5.0 | 150.0 | 10.0 | 0.3 | 1 | 10 | 0.1 | 1.0 |
49 | 4 | 0.0 | missing | missing | 1 | 150.0 | Central | 10.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | missing | missing | missing | 1.5 | 25.0 | 5.0 | 150.0 | 10.0 | 0.3 | 1 | 10 | 0.1 | 1.0 |
50 | 4 | 0.25 | 0.096826 | 9.96663 | 0 | missing | missing | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 2.42065 | 0.0609992 | 9.96663 | 1.5 | 25.0 | 5.0 | 150.0 | 10.0 | 0.3 | 1 | 10 | 0.1 | 1.0 |
51 | 4 | 0.5 | 0.187597 | 9.88839 | 0 | missing | missing | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 4.68993 | 0.238203 | 9.88839 | 1.5 | 25.0 | 5.0 | 150.0 | 10.0 | 0.3 | 1 | 10 | 0.1 | 1.0 |
52 | 4 | 0.75 | 0.272731 | 9.78409 | 0 | missing | missing | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 6.81828 | 0.523374 | 9.78409 | 1.5 | 25.0 | 5.0 | 150.0 | 10.0 | 0.3 | 1 | 10 | 0.1 | 1.0 |
53 | 4 | 1.0 | 0.352616 | 9.66347 | 0 | missing | missing | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 8.8154 | 0.908843 | 9.66347 | 1.5 | 25.0 | 5.0 | 150.0 | 10.0 | 0.3 | 1 | 10 | 0.1 | 1.0 |
54 | 4 | 2.0 | 0.626531 | 9.10546 | 0 | missing | missing | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 15.6633 | 3.31813 | 9.10546 | 1.5 | 25.0 | 5.0 | 150.0 | 10.0 | 0.3 | 1 | 10 | 0.1 | 1.0 |
55 | 4 | 4.0 | 1.01152 | 7.93649 | 0 | missing | missing | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 25.2881 | 11.1916 | 7.93649 | 1.5 | 25.0 | 5.0 | 150.0 | 10.0 | 0.3 | 1 | 10 | 0.1 | 1.0 |
56 | 4 | 8.0 | 1.43067 | 5.95748 | 0 | missing | missing | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 35.7668 | 33.2305 | 5.95748 | 1.5 | 25.0 | 5.0 | 150.0 | 10.0 | 0.3 | 1 | 10 | 0.1 | 1.0 |
57 | 4 | 12.0 | 1.65869 | 4.52562 | 0 | missing | missing | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 41.4673 | 58.211 | 4.52562 | 1.5 | 25.0 | 5.0 | 150.0 | 10.0 | 0.3 | 1 | 10 | 0.1 | 1.0 |
58 | 4 | 16.0 | 1.47042 | 3.52807 | 0 | missing | missing | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 36.7604 | 82.7287 | 3.52807 | 1.5 | 25.0 | 5.0 | 150.0 | 10.0 | 0.3 | 1 | 10 | 0.1 | 1.0 |
59 | 4 | 20.0 | 0.81701 | 3.10522 | 0 | missing | missing | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 20.4252 | 92.5612 | 3.10522 | 1.5 | 25.0 | 5.0 | 150.0 | 10.0 | 0.3 | 1 | 10 | 0.1 | 1.0 |
60 | 4 | 24.0 | 0.599389 | 3.09228 | 0 | missing | missing | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 14.9847 | 93.8667 | 3.09228 | 1.5 | 25.0 | 5.0 | 150.0 | 10.0 | 0.3 | 1 | 10 | 0.1 | 1.0 |
61 | 4 | 36.0 | 0.467029 | 3.55706 | 0 | missing | missing | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 11.6757 | 87.9834 | 3.55706 | 1.5 | 25.0 | 5.0 | 150.0 | 10.0 | 0.3 | 1 | 10 | 0.1 | 1.0 |
62 | 4 | 48.0 | 0.426772 | 3.89715 | 0 | missing | missing | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 10.6693 | 80.9633 | 3.89715 | 1.5 | 25.0 | 5.0 | 150.0 | 10.0 | 0.3 | 1 | 10 | 0.1 | 1.0 |
63 | 4 | 60.0 | 0.392367 | 4.14396 | 0 | missing | missing | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 9.80916 | 74.4559 | 4.14396 | 1.5 | 25.0 | 5.0 | 150.0 | 10.0 | 0.3 | 1 | 10 | 0.1 | 1.0 |
64 | 4 | 71.9 | 0.361073 | 4.36054 | 0 | missing | missing | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 9.02683 | 68.5177 | 4.36054 | 1.5 | 25.0 | 5.0 | 150.0 | 10.0 | 0.3 | 1 | 10 | 0.1 | 1.0 |
65 | 5 | 0.0 | missing | missing | 1 | 150.0 | Central | 10.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | missing | missing | missing | 1.5 | 25.0 | 5.0 | 150.0 | 10.0 | 0.3 | 1 | 10 | 0.1 | 1.0 |
66 | 5 | 0.25 | 0.096826 | 9.96663 | 0 | missing | missing | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 2.42065 | 0.0609992 | 9.96663 | 1.5 | 25.0 | 5.0 | 150.0 | 10.0 | 0.3 | 1 | 10 | 0.1 | 1.0 |
67 | 5 | 0.5 | 0.187597 | 9.88839 | 0 | missing | missing | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 4.68993 | 0.238203 | 9.88839 | 1.5 | 25.0 | 5.0 | 150.0 | 10.0 | 0.3 | 1 | 10 | 0.1 | 1.0 |
68 | 5 | 0.75 | 0.272731 | 9.78409 | 0 | missing | missing | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 6.81828 | 0.523374 | 9.78409 | 1.5 | 25.0 | 5.0 | 150.0 | 10.0 | 0.3 | 1 | 10 | 0.1 | 1.0 |
69 | 5 | 1.0 | 0.352616 | 9.66347 | 0 | missing | missing | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 8.8154 | 0.908843 | 9.66347 | 1.5 | 25.0 | 5.0 | 150.0 | 10.0 | 0.3 | 1 | 10 | 0.1 | 1.0 |
70 | 5 | 2.0 | 0.626531 | 9.10546 | 0 | missing | missing | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 15.6633 | 3.31813 | 9.10546 | 1.5 | 25.0 | 5.0 | 150.0 | 10.0 | 0.3 | 1 | 10 | 0.1 | 1.0 |
71 | 5 | 4.0 | 1.01152 | 7.93649 | 0 | missing | missing | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 25.2881 | 11.1916 | 7.93649 | 1.5 | 25.0 | 5.0 | 150.0 | 10.0 | 0.3 | 1 | 10 | 0.1 | 1.0 |
72 | 5 | 8.0 | 1.43067 | 5.95748 | 0 | missing | missing | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 35.7668 | 33.2305 | 5.95748 | 1.5 | 25.0 | 5.0 | 150.0 | 10.0 | 0.3 | 1 | 10 | 0.1 | 1.0 |
73 | 5 | 12.0 | 1.65869 | 4.52562 | 0 | missing | missing | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 41.4673 | 58.211 | 4.52562 | 1.5 | 25.0 | 5.0 | 150.0 | 10.0 | 0.3 | 1 | 10 | 0.1 | 1.0 |
74 | 5 | 16.0 | 1.47042 | 3.52807 | 0 | missing | missing | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 36.7604 | 82.7287 | 3.52807 | 1.5 | 25.0 | 5.0 | 150.0 | 10.0 | 0.3 | 1 | 10 | 0.1 | 1.0 |
75 | 5 | 20.0 | 0.81701 | 3.10522 | 0 | missing | missing | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 20.4252 | 92.5612 | 3.10522 | 1.5 | 25.0 | 5.0 | 150.0 | 10.0 | 0.3 | 1 | 10 | 0.1 | 1.0 |
76 | 5 | 24.0 | 0.599389 | 3.09228 | 0 | missing | missing | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 14.9847 | 93.8667 | 3.09228 | 1.5 | 25.0 | 5.0 | 150.0 | 10.0 | 0.3 | 1 | 10 | 0.1 | 1.0 |
77 | 5 | 36.0 | 0.467029 | 3.55706 | 0 | missing | missing | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 11.6757 | 87.9834 | 3.55706 | 1.5 | 25.0 | 5.0 | 150.0 | 10.0 | 0.3 | 1 | 10 | 0.1 | 1.0 |
78 | 5 | 48.0 | 0.426772 | 3.89715 | 0 | missing | missing | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 10.6693 | 80.9633 | 3.89715 | 1.5 | 25.0 | 5.0 | 150.0 | 10.0 | 0.3 | 1 | 10 | 0.1 | 1.0 |
79 | 5 | 60.0 | 0.392367 | 4.14396 | 0 | missing | missing | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 9.80916 | 74.4559 | 4.14396 | 1.5 | 25.0 | 5.0 | 150.0 | 10.0 | 0.3 | 1 | 10 | 0.1 | 1.0 |
80 | 5 | 71.9 | 0.361073 | 4.36054 | 0 | missing | missing | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 9.02683 | 68.5177 | 4.36054 | 1.5 | 25.0 | 5.0 | 150.0 | 10.0 | 0.3 | 1 | 10 | 0.1 | 1.0 |
81 | 6 | 0.0 | missing | missing | 1 | 150.0 | Central | 10.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | missing | missing | missing | 1.5 | 25.0 | 5.0 | 150.0 | 10.0 | 0.3 | 1 | 10 | 0.1 | 1.0 |
82 | 6 | 0.25 | 0.096826 | 9.96663 | 0 | missing | missing | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 2.42065 | 0.0609992 | 9.96663 | 1.5 | 25.0 | 5.0 | 150.0 | 10.0 | 0.3 | 1 | 10 | 0.1 | 1.0 |
83 | 6 | 0.5 | 0.187597 | 9.88839 | 0 | missing | missing | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 4.68993 | 0.238203 | 9.88839 | 1.5 | 25.0 | 5.0 | 150.0 | 10.0 | 0.3 | 1 | 10 | 0.1 | 1.0 |
84 | 6 | 0.75 | 0.272731 | 9.78409 | 0 | missing | missing | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 6.81828 | 0.523374 | 9.78409 | 1.5 | 25.0 | 5.0 | 150.0 | 10.0 | 0.3 | 1 | 10 | 0.1 | 1.0 |
85 | 6 | 1.0 | 0.352616 | 9.66347 | 0 | missing | missing | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 8.8154 | 0.908843 | 9.66347 | 1.5 | 25.0 | 5.0 | 150.0 | 10.0 | 0.3 | 1 | 10 | 0.1 | 1.0 |
86 | 6 | 2.0 | 0.626531 | 9.10546 | 0 | missing | missing | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 15.6633 | 3.31813 | 9.10546 | 1.5 | 25.0 | 5.0 | 150.0 | 10.0 | 0.3 | 1 | 10 | 0.1 | 1.0 |
87 | 6 | 4.0 | 1.01152 | 7.93649 | 0 | missing | missing | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 25.2881 | 11.1916 | 7.93649 | 1.5 | 25.0 | 5.0 | 150.0 | 10.0 | 0.3 | 1 | 10 | 0.1 | 1.0 |
88 | 6 | 8.0 | 1.43067 | 5.95748 | 0 | missing | missing | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 35.7668 | 33.2305 | 5.95748 | 1.5 | 25.0 | 5.0 | 150.0 | 10.0 | 0.3 | 1 | 10 | 0.1 | 1.0 |
89 | 6 | 12.0 | 1.65869 | 4.52562 | 0 | missing | missing | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 41.4673 | 58.211 | 4.52562 | 1.5 | 25.0 | 5.0 | 150.0 | 10.0 | 0.3 | 1 | 10 | 0.1 | 1.0 |
90 | 6 | 16.0 | 1.47042 | 3.52807 | 0 | missing | missing | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 36.7604 | 82.7287 | 3.52807 | 1.5 | 25.0 | 5.0 | 150.0 | 10.0 | 0.3 | 1 | 10 | 0.1 | 1.0 |
91 | 6 | 20.0 | 0.81701 | 3.10522 | 0 | missing | missing | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 20.4252 | 92.5612 | 3.10522 | 1.5 | 25.0 | 5.0 | 150.0 | 10.0 | 0.3 | 1 | 10 | 0.1 | 1.0 |
92 | 6 | 24.0 | 0.599389 | 3.09228 | 0 | missing | missing | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 14.9847 | 93.8667 | 3.09228 | 1.5 | 25.0 | 5.0 | 150.0 | 10.0 | 0.3 | 1 | 10 | 0.1 | 1.0 |
93 | 6 | 36.0 | 0.467029 | 3.55706 | 0 | missing | missing | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 11.6757 | 87.9834 | 3.55706 | 1.5 | 25.0 | 5.0 | 150.0 | 10.0 | 0.3 | 1 | 10 | 0.1 | 1.0 |
94 | 6 | 48.0 | 0.426772 | 3.89715 | 0 | missing | missing | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 10.6693 | 80.9633 | 3.89715 | 1.5 | 25.0 | 5.0 | 150.0 | 10.0 | 0.3 | 1 | 10 | 0.1 | 1.0 |
95 | 6 | 60.0 | 0.392367 | 4.14396 | 0 | missing | missing | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 9.80916 | 74.4559 | 4.14396 | 1.5 | 25.0 | 5.0 | 150.0 | 10.0 | 0.3 | 1 | 10 | 0.1 | 1.0 |
96 | 6 | 71.9 | 0.361073 | 4.36054 | 0 | missing | missing | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 9.02683 | 68.5177 | 4.36054 | 1.5 | 25.0 | 5.0 | 150.0 | 10.0 | 0.3 | 1 | 10 | 0.1 | 1.0 |
97 | 7 | 0.0 | missing | missing | 1 | 150.0 | Central | 10.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | missing | missing | missing | 1.5 | 25.0 | 5.0 | 150.0 | 10.0 | 0.3 | 1 | 10 | 0.1 | 1.0 |
98 | 7 | 0.25 | 0.096826 | 9.96663 | 0 | missing | missing | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 2.42065 | 0.0609992 | 9.96663 | 1.5 | 25.0 | 5.0 | 150.0 | 10.0 | 0.3 | 1 | 10 | 0.1 | 1.0 |
99 | 7 | 0.5 | 0.187597 | 9.88839 | 0 | missing | missing | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 4.68993 | 0.238203 | 9.88839 | 1.5 | 25.0 | 5.0 | 150.0 | 10.0 | 0.3 | 1 | 10 | 0.1 | 1.0 |
100 | 7 | 0.75 | 0.272731 | 9.78409 | 0 | missing | missing | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 6.81828 | 0.523374 | 9.78409 | 1.5 | 25.0 | 5.0 | 150.0 | 10.0 | 0.3 | 1 | 10 | 0.1 | 1.0 |
101 | 7 | 1.0 | 0.352616 | 9.66347 | 0 | missing | missing | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 8.8154 | 0.908843 | 9.66347 | 1.5 | 25.0 | 5.0 | 150.0 | 10.0 | 0.3 | 1 | 10 | 0.1 | 1.0 |
102 | 7 | 2.0 | 0.626531 | 9.10546 | 0 | missing | missing | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 15.6633 | 3.31813 | 9.10546 | 1.5 | 25.0 | 5.0 | 150.0 | 10.0 | 0.3 | 1 | 10 | 0.1 | 1.0 |
103 | 7 | 4.0 | 1.01152 | 7.93649 | 0 | missing | missing | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 25.2881 | 11.1916 | 7.93649 | 1.5 | 25.0 | 5.0 | 150.0 | 10.0 | 0.3 | 1 | 10 | 0.1 | 1.0 |
104 | 7 | 8.0 | 1.43067 | 5.95748 | 0 | missing | missing | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 35.7668 | 33.2305 | 5.95748 | 1.5 | 25.0 | 5.0 | 150.0 | 10.0 | 0.3 | 1 | 10 | 0.1 | 1.0 |
105 | 7 | 12.0 | 1.65869 | 4.52562 | 0 | missing | missing | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 41.4673 | 58.211 | 4.52562 | 1.5 | 25.0 | 5.0 | 150.0 | 10.0 | 0.3 | 1 | 10 | 0.1 | 1.0 |
106 | 7 | 16.0 | 1.47042 | 3.52807 | 0 | missing | missing | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 36.7604 | 82.7287 | 3.52807 | 1.5 | 25.0 | 5.0 | 150.0 | 10.0 | 0.3 | 1 | 10 | 0.1 | 1.0 |
107 | 7 | 20.0 | 0.81701 | 3.10522 | 0 | missing | missing | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 20.4252 | 92.5612 | 3.10522 | 1.5 | 25.0 | 5.0 | 150.0 | 10.0 | 0.3 | 1 | 10 | 0.1 | 1.0 |
108 | 7 | 24.0 | 0.599389 | 3.09228 | 0 | missing | missing | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 14.9847 | 93.8667 | 3.09228 | 1.5 | 25.0 | 5.0 | 150.0 | 10.0 | 0.3 | 1 | 10 | 0.1 | 1.0 |
109 | 7 | 36.0 | 0.467029 | 3.55706 | 0 | missing | missing | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 11.6757 | 87.9834 | 3.55706 | 1.5 | 25.0 | 5.0 | 150.0 | 10.0 | 0.3 | 1 | 10 | 0.1 | 1.0 |
110 | 7 | 48.0 | 0.426772 | 3.89715 | 0 | missing | missing | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 10.6693 | 80.9633 | 3.89715 | 1.5 | 25.0 | 5.0 | 150.0 | 10.0 | 0.3 | 1 | 10 | 0.1 | 1.0 |
111 | 7 | 60.0 | 0.392367 | 4.14396 | 0 | missing | missing | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 9.80916 | 74.4559 | 4.14396 | 1.5 | 25.0 | 5.0 | 150.0 | 10.0 | 0.3 | 1 | 10 | 0.1 | 1.0 |
112 | 7 | 71.9 | 0.361073 | 4.36054 | 0 | missing | missing | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 9.02683 | 68.5177 | 4.36054 | 1.5 | 25.0 | 5.0 | 150.0 | 10.0 | 0.3 | 1 | 10 | 0.1 | 1.0 |
113 | 8 | 0.0 | missing | missing | 1 | 150.0 | Central | 10.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | missing | missing | missing | 1.5 | 25.0 | 5.0 | 150.0 | 10.0 | 0.3 | 1 | 10 | 0.1 | 1.0 |
114 | 8 | 0.25 | 0.096826 | 9.96663 | 0 | missing | missing | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 2.42065 | 0.0609992 | 9.96663 | 1.5 | 25.0 | 5.0 | 150.0 | 10.0 | 0.3 | 1 | 10 | 0.1 | 1.0 |
115 | 8 | 0.5 | 0.187597 | 9.88839 | 0 | missing | missing | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 4.68993 | 0.238203 | 9.88839 | 1.5 | 25.0 | 5.0 | 150.0 | 10.0 | 0.3 | 1 | 10 | 0.1 | 1.0 |
116 | 8 | 0.75 | 0.272731 | 9.78409 | 0 | missing | missing | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 6.81828 | 0.523374 | 9.78409 | 1.5 | 25.0 | 5.0 | 150.0 | 10.0 | 0.3 | 1 | 10 | 0.1 | 1.0 |
117 | 8 | 1.0 | 0.352616 | 9.66347 | 0 | missing | missing | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 8.8154 | 0.908843 | 9.66347 | 1.5 | 25.0 | 5.0 | 150.0 | 10.0 | 0.3 | 1 | 10 | 0.1 | 1.0 |
118 | 8 | 2.0 | 0.626531 | 9.10546 | 0 | missing | missing | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 15.6633 | 3.31813 | 9.10546 | 1.5 | 25.0 | 5.0 | 150.0 | 10.0 | 0.3 | 1 | 10 | 0.1 | 1.0 |
119 | 8 | 4.0 | 1.01152 | 7.93649 | 0 | missing | missing | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 25.2881 | 11.1916 | 7.93649 | 1.5 | 25.0 | 5.0 | 150.0 | 10.0 | 0.3 | 1 | 10 | 0.1 | 1.0 |
120 | 8 | 8.0 | 1.43067 | 5.95748 | 0 | missing | missing | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 35.7668 | 33.2305 | 5.95748 | 1.5 | 25.0 | 5.0 | 150.0 | 10.0 | 0.3 | 1 | 10 | 0.1 | 1.0 |
121 | 8 | 12.0 | 1.65869 | 4.52562 | 0 | missing | missing | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 41.4673 | 58.211 | 4.52562 | 1.5 | 25.0 | 5.0 | 150.0 | 10.0 | 0.3 | 1 | 10 | 0.1 | 1.0 |
122 | 8 | 16.0 | 1.47042 | 3.52807 | 0 | missing | missing | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 36.7604 | 82.7287 | 3.52807 | 1.5 | 25.0 | 5.0 | 150.0 | 10.0 | 0.3 | 1 | 10 | 0.1 | 1.0 |
123 | 8 | 20.0 | 0.81701 | 3.10522 | 0 | missing | missing | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 20.4252 | 92.5612 | 3.10522 | 1.5 | 25.0 | 5.0 | 150.0 | 10.0 | 0.3 | 1 | 10 | 0.1 | 1.0 |
124 | 8 | 24.0 | 0.599389 | 3.09228 | 0 | missing | missing | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 14.9847 | 93.8667 | 3.09228 | 1.5 | 25.0 | 5.0 | 150.0 | 10.0 | 0.3 | 1 | 10 | 0.1 | 1.0 |
125 | 8 | 36.0 | 0.467029 | 3.55706 | 0 | missing | missing | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 11.6757 | 87.9834 | 3.55706 | 1.5 | 25.0 | 5.0 | 150.0 | 10.0 | 0.3 | 1 | 10 | 0.1 | 1.0 |
126 | 8 | 48.0 | 0.426772 | 3.89715 | 0 | missing | missing | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 10.6693 | 80.9633 | 3.89715 | 1.5 | 25.0 | 5.0 | 150.0 | 10.0 | 0.3 | 1 | 10 | 0.1 | 1.0 |
127 | 8 | 60.0 | 0.392367 | 4.14396 | 0 | missing | missing | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 9.80916 | 74.4559 | 4.14396 | 1.5 | 25.0 | 5.0 | 150.0 | 10.0 | 0.3 | 1 | 10 | 0.1 | 1.0 |
128 | 8 | 71.9 | 0.361073 | 4.36054 | 0 | missing | missing | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 9.02683 | 68.5177 | 4.36054 | 1.5 | 25.0 | 5.0 | 150.0 | 10.0 | 0.3 | 1 | 10 | 0.1 | 1.0 |
129 | 9 | 0.0 | missing | missing | 1 | 150.0 | Central | 10.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | missing | missing | missing | 1.5 | 25.0 | 5.0 | 150.0 | 10.0 | 0.3 | 1 | 10 | 0.1 | 1.0 |
130 | 9 | 0.25 | 0.096826 | 9.96663 | 0 | missing | missing | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 2.42065 | 0.0609992 | 9.96663 | 1.5 | 25.0 | 5.0 | 150.0 | 10.0 | 0.3 | 1 | 10 | 0.1 | 1.0 |
131 | 9 | 0.5 | 0.187597 | 9.88839 | 0 | missing | missing | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 4.68993 | 0.238203 | 9.88839 | 1.5 | 25.0 | 5.0 | 150.0 | 10.0 | 0.3 | 1 | 10 | 0.1 | 1.0 |
132 | 9 | 0.75 | 0.272731 | 9.78409 | 0 | missing | missing | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 6.81828 | 0.523374 | 9.78409 | 1.5 | 25.0 | 5.0 | 150.0 | 10.0 | 0.3 | 1 | 10 | 0.1 | 1.0 |
133 | 9 | 1.0 | 0.352616 | 9.66347 | 0 | missing | missing | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 8.8154 | 0.908843 | 9.66347 | 1.5 | 25.0 | 5.0 | 150.0 | 10.0 | 0.3 | 1 | 10 | 0.1 | 1.0 |
134 | 9 | 2.0 | 0.626531 | 9.10546 | 0 | missing | missing | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 15.6633 | 3.31813 | 9.10546 | 1.5 | 25.0 | 5.0 | 150.0 | 10.0 | 0.3 | 1 | 10 | 0.1 | 1.0 |
135 | 9 | 4.0 | 1.01152 | 7.93649 | 0 | missing | missing | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 25.2881 | 11.1916 | 7.93649 | 1.5 | 25.0 | 5.0 | 150.0 | 10.0 | 0.3 | 1 | 10 | 0.1 | 1.0 |
136 | 9 | 8.0 | 1.43067 | 5.95748 | 0 | missing | missing | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 35.7668 | 33.2305 | 5.95748 | 1.5 | 25.0 | 5.0 | 150.0 | 10.0 | 0.3 | 1 | 10 | 0.1 | 1.0 |
137 | 9 | 12.0 | 1.65869 | 4.52562 | 0 | missing | missing | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 41.4673 | 58.211 | 4.52562 | 1.5 | 25.0 | 5.0 | 150.0 | 10.0 | 0.3 | 1 | 10 | 0.1 | 1.0 |
138 | 9 | 16.0 | 1.47042 | 3.52807 | 0 | missing | missing | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 36.7604 | 82.7287 | 3.52807 | 1.5 | 25.0 | 5.0 | 150.0 | 10.0 | 0.3 | 1 | 10 | 0.1 | 1.0 |
139 | 9 | 20.0 | 0.81701 | 3.10522 | 0 | missing | missing | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 20.4252 | 92.5612 | 3.10522 | 1.5 | 25.0 | 5.0 | 150.0 | 10.0 | 0.3 | 1 | 10 | 0.1 | 1.0 |
140 | 9 | 24.0 | 0.599389 | 3.09228 | 0 | missing | missing | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 14.9847 | 93.8667 | 3.09228 | 1.5 | 25.0 | 5.0 | 150.0 | 10.0 | 0.3 | 1 | 10 | 0.1 | 1.0 |
141 | 9 | 36.0 | 0.467029 | 3.55706 | 0 | missing | missing | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 11.6757 | 87.9834 | 3.55706 | 1.5 | 25.0 | 5.0 | 150.0 | 10.0 | 0.3 | 1 | 10 | 0.1 | 1.0 |
142 | 9 | 48.0 | 0.426772 | 3.89715 | 0 | missing | missing | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 10.6693 | 80.9633 | 3.89715 | 1.5 | 25.0 | 5.0 | 150.0 | 10.0 | 0.3 | 1 | 10 | 0.1 | 1.0 |
143 | 9 | 60.0 | 0.392367 | 4.14396 | 0 | missing | missing | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 9.80916 | 74.4559 | 4.14396 | 1.5 | 25.0 | 5.0 | 150.0 | 10.0 | 0.3 | 1 | 10 | 0.1 | 1.0 |
144 | 9 | 71.9 | 0.361073 | 4.36054 | 0 | missing | missing | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 9.02683 | 68.5177 | 4.36054 | 1.5 | 25.0 | 5.0 | 150.0 | 10.0 | 0.3 | 1 | 10 | 0.1 | 1.0 |
145 | 10 | 0.0 | missing | missing | 1 | 150.0 | Central | 10.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | missing | missing | missing | 1.5 | 25.0 | 5.0 | 150.0 | 10.0 | 0.3 | 1 | 10 | 0.1 | 1.0 |
146 | 10 | 0.25 | 0.096826 | 9.96663 | 0 | missing | missing | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 2.42065 | 0.0609992 | 9.96663 | 1.5 | 25.0 | 5.0 | 150.0 | 10.0 | 0.3 | 1 | 10 | 0.1 | 1.0 |
147 | 10 | 0.5 | 0.187597 | 9.88839 | 0 | missing | missing | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 4.68993 | 0.238203 | 9.88839 | 1.5 | 25.0 | 5.0 | 150.0 | 10.0 | 0.3 | 1 | 10 | 0.1 | 1.0 |
148 | 10 | 0.75 | 0.272731 | 9.78409 | 0 | missing | missing | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 6.81828 | 0.523374 | 9.78409 | 1.5 | 25.0 | 5.0 | 150.0 | 10.0 | 0.3 | 1 | 10 | 0.1 | 1.0 |
149 | 10 | 1.0 | 0.352616 | 9.66347 | 0 | missing | missing | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 8.8154 | 0.908843 | 9.66347 | 1.5 | 25.0 | 5.0 | 150.0 | 10.0 | 0.3 | 1 | 10 | 0.1 | 1.0 |
150 | 10 | 2.0 | 0.626531 | 9.10546 | 0 | missing | missing | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 15.6633 | 3.31813 | 9.10546 | 1.5 | 25.0 | 5.0 | 150.0 | 10.0 | 0.3 | 1 | 10 | 0.1 | 1.0 |
151 | 10 | 4.0 | 1.01152 | 7.93649 | 0 | missing | missing | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 25.2881 | 11.1916 | 7.93649 | 1.5 | 25.0 | 5.0 | 150.0 | 10.0 | 0.3 | 1 | 10 | 0.1 | 1.0 |
152 | 10 | 8.0 | 1.43067 | 5.95748 | 0 | missing | missing | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 35.7668 | 33.2305 | 5.95748 | 1.5 | 25.0 | 5.0 | 150.0 | 10.0 | 0.3 | 1 | 10 | 0.1 | 1.0 |
153 | 10 | 12.0 | 1.65869 | 4.52562 | 0 | missing | missing | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 41.4673 | 58.211 | 4.52562 | 1.5 | 25.0 | 5.0 | 150.0 | 10.0 | 0.3 | 1 | 10 | 0.1 | 1.0 |
154 | 10 | 16.0 | 1.47042 | 3.52807 | 0 | missing | missing | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 36.7604 | 82.7287 | 3.52807 | 1.5 | 25.0 | 5.0 | 150.0 | 10.0 | 0.3 | 1 | 10 | 0.1 | 1.0 |
155 | 10 | 20.0 | 0.81701 | 3.10522 | 0 | missing | missing | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 20.4252 | 92.5612 | 3.10522 | 1.5 | 25.0 | 5.0 | 150.0 | 10.0 | 0.3 | 1 | 10 | 0.1 | 1.0 |
156 | 10 | 24.0 | 0.599389 | 3.09228 | 0 | missing | missing | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 14.9847 | 93.8667 | 3.09228 | 1.5 | 25.0 | 5.0 | 150.0 | 10.0 | 0.3 | 1 | 10 | 0.1 | 1.0 |
157 | 10 | 36.0 | 0.467029 | 3.55706 | 0 | missing | missing | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 11.6757 | 87.9834 | 3.55706 | 1.5 | 25.0 | 5.0 | 150.0 | 10.0 | 0.3 | 1 | 10 | 0.1 | 1.0 |
158 | 10 | 48.0 | 0.426772 | 3.89715 | 0 | missing | missing | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 10.6693 | 80.9633 | 3.89715 | 1.5 | 25.0 | 5.0 | 150.0 | 10.0 | 0.3 | 1 | 10 | 0.1 | 1.0 |
159 | 10 | 60.0 | 0.392367 | 4.14396 | 0 | missing | missing | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 9.80916 | 74.4559 | 4.14396 | 1.5 | 25.0 | 5.0 | 150.0 | 10.0 | 0.3 | 1 | 10 | 0.1 | 1.0 |
160 | 10 | 71.9 | 0.361073 | 4.36054 | 0 | missing | missing | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 9.02683 | 68.5177 | 4.36054 | 1.5 | 25.0 | 5.0 | 150.0 | 10.0 | 0.3 | 1 | 10 | 0.1 | 1.0 |
From there, any Julia tools can be used to analyze these arrays and DataFrame
s.
Conducting an Estimation
With a model and population you can fit your model. Model fitting in Pumas has the purpose of estimate parameters and is done by calling the fit
function with the following positional arguments:
- a Pumas model.
- a
Population
or aSubject
. - a named tuple of the initial parameter values.
- an inference algorithm.
If you want to use the model's initial parameter values declared inside the @param
block, you can do so with init_params(model)
. Note that this will fall back to the parameters' default values if you do not specify an initial value inside the @param
block.
Pumas supports the following inference algorithms:
- Maximum Likelihood Estimation:
NaivePooled()
: first order approximation without random-effects.FO()
: first-order approximation.FOCE()
: first-order conditional estimation.LaplaceI()
: second-order Laplace approximation.- SAEM: Stochastic Approximation using the Expectation-Maximization algorithm. Note that you need an
@emmodel
instead of a@model
.
- Bayesian inference:
BayesMCMC()
: MCMC using No-U-Turn Sampler (NUTS).MAP()
: Maximum A Posteriori estimation.
Now we can fit our model using one of the simulated populations from the previous section:
turnover_params = (
tvcl = 1.5,
tvvc = 25.0,
tvq = 5.0,
tvvp = 150.0,
tvturn = 10,
tvebase = 10,
tvec50 = 0.3,
Ω_pk = Diagonal([0.05, 0.05, 0.05, 0.05]),
Ω_pd = Diagonal([0.05]),
σ_prop_pk = 0.15,
σ_add_pk = 0.5,
σ_add_pd = 0.2
)
sims = simobs(
inf_2cmt_lin_turnover,
pop,
turnover_params,
obstimes = sd_obstimes,
rng = StableRNG(123)
)
Simulated population (Vector{<:Subject})
Simulated subjects: 10
Simulated variables: dv, resp
fit_2cmt_lin_turnover = fit(
inf_2cmt_lin_turnover,
Subject.(sims),
init_params(inf_2cmt_lin_turnover),
Pumas.FOCE()
)
FittedPumasModel
Successful minimization: false
Likelihood approximation: FOCE
Log-likelihood value: -136.79299
Number of subjects: 10
Number of parameters: Fixed Optimized
0 15
Observation records: Active Missing
dv: 150 0
resp: 150 0
Total: 300 0
------------------------
Estimate
------------------------
tvcl 1.6271
tvvc 20.756
tvq 4.0536
tvvp 109.18
Ω_pk₁,₁ 0.041113
Ω_pk₂,₂ 0.091622
Ω_pk₃,₃ 0.036201
Ω_pk₄,₄ 0.027388
σ_prop_pk 0.070826
σ_add_pk 0.46577
tvturn 9.9485
tvebase 11.123
tvec50 0.32579
Ω_pd₁,₁ 0.069718
σ_add_pd 0.2002
------------------------
Calculating confidence intervals and Bootstrap
You can calculate confidence intervals using the infer
function (by default 95% CIs):
infer_2cmt_lin_turnover = infer(fit_2cmt_lin_turnover)
Asymptotic inference results using sandwich estimator
Successful minimization: false
Likelihood approximation: FOCE
Log-likelihood value: -136.79299
Number of subjects: 10
Number of parameters: Fixed Optimized
0 15
Observation records: Active Missing
dv: 150 0
resp: 150 0
Total: 300 0
----------------------------------------------------------------------
Estimate SE 95.0% C.I.
----------------------------------------------------------------------
tvcl 1.6271 0.21575 [ 1.2042 ; 2.0499 ]
tvvc 20.756 2.3862 [16.079 ; 25.433 ]
tvq 4.0536 0.3733 [ 3.322 ; 4.7853 ]
tvvp 109.18 10.902 [87.809 ; 130.54 ]
Ω_pk₁,₁ 0.041113 0.023954 [-0.0058348; 0.088062]
Ω_pk₂,₂ 0.091622 0.048108 [-0.0026677; 0.18591 ]
Ω_pk₃,₃ 0.036201 0.032672 [-0.027835 ; 0.10024 ]
Ω_pk₄,₄ 0.027388 0.025894 [-0.023363 ; 0.078138]
σ_prop_pk 0.070826 0.17206 [-0.2664 ; 0.40805 ]
σ_add_pk 0.46577 0.045775 [ 0.37605 ; 0.55549 ]
tvturn 9.9485 0.38629 [ 9.1914 ; 10.706 ]
tvebase 11.123 0.93216 [ 9.2961 ; 12.95 ]
tvec50 0.32579 0.027227 [ 0.27243 ; 0.37916 ]
Ω_pd₁,₁ 0.069718 0.01392 [ 0.042436 ; 0.097 ]
σ_add_pd 0.2002 0.014756 [ 0.17127 ; 0.22912 ]
----------------------------------------------------------------------
You can also convert the output to a DataFrame
with the coeftable
function:
coeftable(infer_2cmt_lin_turnover)
15 rows × 5 columns
parameter | estimate | se | ci_lower | ci_upper | |
---|---|---|---|---|---|
String | Float64 | Float64 | Float64 | Float64 | |
1 | tvcl | 1.62709 | 0.215747 | 1.20423 | 2.04995 |
2 | tvvc | 20.7564 | 2.38624 | 16.0795 | 25.4334 |
3 | tvq | 4.05362 | 0.373304 | 3.32196 | 4.78529 |
4 | tvvp | 109.177 | 10.9022 | 87.809 | 130.545 |
5 | Ω_pk₁,₁ | 0.0411134 | 0.0239536 | -0.00583483 | 0.0880617 |
6 | Ω_pk₂,₂ | 0.091622 | 0.0481079 | -0.00266774 | 0.185912 |
7 | Ω_pk₃,₃ | 0.0362006 | 0.0326718 | -0.027835 | 0.100236 |
8 | Ω_pk₄,₄ | 0.0273876 | 0.0258936 | -0.0233628 | 0.078138 |
9 | σ_prop_pk | 0.0708259 | 0.172058 | -0.266401 | 0.408053 |
10 | σ_add_pk | 0.465769 | 0.0457747 | 0.376052 | 0.555485 |
11 | tvturn | 9.94848 | 0.386294 | 9.19136 | 10.7056 |
12 | tvebase | 11.1231 | 0.932162 | 9.29613 | 12.9501 |
13 | tvec50 | 0.325793 | 0.0272274 | 0.272429 | 0.379158 |
14 | Ω_pd₁,₁ | 0.0697176 | 0.0139197 | 0.0424355 | 0.0969997 |
15 | σ_add_pd | 0.200195 | 0.0147559 | 0.171274 | 0.229116 |
For inference with bootstrap-based confidence intervals you can use Pumas.Bootstrap
as an optional second positional argument in infer
(by default the number of samples is 200):
infer_boot_2cmt_lin_turnover = infer(fit_2cmt_lin_turnover, Pumas.Bootstrap(ensemblealg=EnsembleThreads()))
┌ Info: Bootstrap inference finished.
│ Total resampled fits = 200
│ Success rate = 1.0
└ Unique resampled populations = 200
Bootstrap inference results
Successful minimization: true
Likelihood approximation: Pumas.FOCE
Log-likelihood value: -144.42225
Number of subjects: 10
Number of parameters: Fixed Optimized
0 15
Observation records: Active Missing
dv: 150 0
resp: 150 0
Total: 300 0
----------------------------------------------------------------------
Estimate SE 95.0% C.I.
----------------------------------------------------------------------
tvcl 1.1668 0.30297 [ 0.55865 ; 1.5918 ]
tvvc 23.26 4.1501 [ 18.107 ; 32.552 ]
tvq 5.1594 0.49696 [ 4.3548 ; 6.2169 ]
tvvp 171.12 49.577 [119.58 ; 308.94 ]
Ω_pk₁,₁ 0.038306 1.599 [ 2.2387e-16; 0.10429 ]
Ω_pk₂,₂ 0.086399 0.044714 [ 1.1596e-9 ; 0.17843 ]
Ω_pk₃,₃ 0.023877 0.012185 [ 5.6738e-18; 0.043998]
Ω_pk₄,₄ 0.093753 0.044657 [ 0.010312 ; 0.17991 ]
σ_prop_pk 0.076458 0.076803 [ 1.9102e-10; 0.21935 ]
σ_add_pk 0.51079 0.03356 [ 0.4362 ; 0.55698 ]
tvturn 10.221 0.59544 [ 9.016 ; 11.213 ]
tvebase 9.5673 0.64726 [ 8.3718 ; 10.83 ]
tvec50 0.30015 0.037184 [ 0.23985 ; 0.38186 ]
Ω_pd₁,₁ 0.047302 0.013862 [ 0.016567 ; 0.069705]
σ_add_pd 0.20055 0.011621 [ 0.17741 ; 0.2248 ]
----------------------------------------------------------------------
Successful fits: 200 out of 200
Unique resampled populations: 200
No stratification.
You can also convert the inference results to a DataFrame
with coeftable
:
coeftable(infer_boot_2cmt_lin_turnover)
julia> coeftable(infer_boot_2cmt_lin_turnover)
15×5 DataFrame
Row │ parameter estimate se ci_lower ci_upper
│ String Float64 Float64 Float64 Float64
─────┼────────────────────────────────────────────────────────────────
1 │ tvcl 1.16678 0.302968 0.558649 1.59179
2 │ tvvc 23.2605 4.15007 18.1071 32.5522
3 │ tvq 5.15943 0.496956 4.35485 6.21692
4 │ tvvp 171.116 49.5771 119.585 308.94
5 │ Ω_pk₁,₁ 0.0383064 1.59895 2.2387e-16 0.10429
6 │ Ω_pk₂,₂ 0.0863987 0.0447138 1.15956e-9 0.178432
7 │ Ω_pk₃,₃ 0.0238772 0.0121848 5.67381e-18 0.0439976
8 │ Ω_pk₄,₄ 0.093753 0.0446573 0.0103117 0.179912
9 │ σ_prop_pk 0.0764577 0.0768028 1.9102e-10 0.219353
10 │ σ_add_pk 0.510786 0.0335596 0.436204 0.556977
11 │ tvturn 10.2212 0.595444 9.01602 11.2135
12 │ tvebase 9.56727 0.647258 8.37178 10.8296
13 │ tvec50 0.300155 0.0371844 0.239847 0.381857
14 │ Ω_pd₁,₁ 0.0473021 0.0138622 0.0165671 0.0697046
15 │ σ_add_pd 0.200548 0.011621 0.177408 0.224798
Conclusion
This tutorial covered the basic workflow of building a model, simulating results from it, and conducting an estimation. The subsequent tutorials will discuss the components in more detail, such as:
- More detailed treatment of specifying populations, dosage regimens, and covariates.
- Reading in dosage regimens and observations from standard input data.
- Fitting models with different estimation methods.