Simulate ODE or analytical equation

Simulates a specified regimen using ODE system or analytical equation

Usage

sim(
  ode = NULL,
  analytical = NULL,
  parameters = NULL,
  parameters_table = NULL,
  mixture_group = NULL,
  omega = NULL,
  omega_type = "exponential",
  res_var = NULL,
  iov_bins = NULL,
  seed = NULL,
  sequence = NULL,
  n_ind = 1,
  event_table = NULL,
  regimen = NULL,
  lagtime = NULL,
  covariates = NULL,
  covariates_table = NULL,
  covariates_implementation = list(),
  covariate_model = NULL,
  A_init = NULL,
  only_obs = FALSE,
  obs_step_size = NULL,
  int_step_size = 0.01,
  t_max = NULL,
  t_obs = NULL,
  t_tte = NULL,
  t_init = 0,
  obs_type = NULL,
  duplicate_t_obs = FALSE,
  extra_t_obs = TRUE,
  rtte = FALSE,
  checks = TRUE,
  verbose = FALSE,
  return_event_table = FALSE,
  return_design = FALSE,
  output_include = list(parameters = FALSE, covariates = FALSE),
  ...
)

Arguments

ode: function describing the ODE system
analytical: string specifying analytical equation model to use (similar to ADVAN1-5 in NONMEM). If specified, will not use ODEs.
parameters: model parameters
parameters_table: dataframe of parameters (with parameters as columns) containing parameter estimates for individuals to simulate. Formats accepted: data.frame, data.table, or list of lists.
mixture_group: mixture group for models containing mixtures. Should be either 1 or 2, since only two groups are currently allowed.
omega: vector describing the lower-diagonal of the between-subject variability matrix
omega_type: exponential or normal, specified as vector
res_var: residual variability. Expected a list with arguments prop, add, and/or exp. NULL by default.
iov_bins: allow override of the default IOV bins for a model. Specified as a vector of timepoints specifying the bin separators, e.g. iov_bins = c(0, 24, 48, 72, 9999). A warning will be thrown when less bins are requested than was defined for the model during compilation. When the number of bins is higher than defined for the model an error will be thrown.
seed: set seed for reproducible results
sequence: if not NULL specifies the pseudo-random sequence to use, e.g. "halton" or "sobol". See mvrnorm2 for more details.
n_ind: number of individuals to simulate
event_table: use a previously created design object used for ODE simulation instead of calling create_event_table() to create a new one. Especially useful for repeated calling of sim(), such as in optimizations or optimal design analysis. Also see sim_core() for even faster simulations using precalculated design objects.
regimen: a regimen object created using the regimen() function
lagtime: either a value (numeric) or a parameter (character) or NULL.
covariates: list of covariates (for single individual) created using new_covariate() function
covariates_table: data.frame (or unnamed list of named lists per individual) with covariate values
covariates_implementation: used only for covariates_table, a named list of covariate implementation methods per covariate, e.g. list(WT = "interpolate", BIN = "locf")
covariate_model: R code used to pre-calculate effective parameters for use in ADVAN-style analytical equations. Not used in ODE simulations.
A_init: vector with the initial state of the ODE system
only_obs: only return the observations
obs_step_size: the step size between the observations
int_step_size: the step size for the numerical integrator
t_max: maximum simulation time, if not specified will pick the end of the regimen as maximum
t_obs: vector of observation times, only output these values (only used when t_obs==NULL)
t_tte: vector of observation times for time-to-event simulation
t_init: initialization time before first dose, default 0.
obs_type: vector of observation types. Only valid in combination with equal length vector t_obs.
duplicate_t_obs: allow duplicate t_obs in output? E.g. for optimal design calculations when t_obs = c(0,1,2,2,3). Default is FALSE.
extra_t_obs: include extra t_obs in output for bolus doses? This is only activated when t_obs is not specified manually. E.g. for a bolus dose at t=24, if FALSE, PKPDsim will output only the trough, so for bolus doses you might want to switch this setting to TRUE. When set to "auto" (default), it will be TRUE by default, but will switch to FALSE whenever t_obs is specified manually.
rtte: should repeated events be allowed (FALSE by default)
checks: perform input checks? Default is TRUE. For calculations where sim_ode is invoked many times (e.g. population estimation, optimal design) it makes sense to switch this to FALSE (after confirming the input is correct) to improve speed.
verbose: show more output
return_event_table: return the event table for the simulation only, does not run the actual simulation. Useful for iterative use of sim().
return_design: returns the design (event table and several other details) for the simulation, does not run the actual simulation. Useful for iterative functions like estimation in combination with sim_core(), e.g. for estimation and optimal design.
output_include: list specifying what to include in output table, with keys parameters and covariates. Both are FALSE by default.
...: extra parameters

Value

a data frame of compartments with associated concentrations at requested times

Simulated regimen

Examples

# \donttest{
p <- list(
  CL = 38.48,
  V  = 7.4,
  Q  = 7.844,
  V2 = 5.19,
  Q2  = 9.324,
  V3 = 111
)

omega <- c(0.3,       # IIV CL
           0.1, 0.3)  # IIV V

r1 <- new_regimen(
  amt = 100,
  times = c(0, 24, 36),
  type = "infusion"
)

mod <- new_ode_model("pk_3cmt_iv")
dat <- sim(
  ode = mod,
  parameters = p,
  omega = omega,
  n_ind = 20,
  regimen = r1
)
# }

Simulate ODE or analytical equation

Usage

Arguments

Value

See also

Examples