get_params_flat: Get parameters to be optimized for flat model

Description

The full set of model parameters for the flat model includes `Vdist`, `Fgutabs`, and `Rblood2plasma`. Whether each one can be estimated from the data depends on what routes of administration are included in the data.

Usage

get_params_flat(
  data,
  lower_bound = NULL,
  upper_bound = NULL,
  param_units = alist(Vdist = paste0("(", unique(Dose.Units), ")/(", unique(Conc.Units),
    ")"), Fgutabs = "unitless fraction", Fgutabs_Vdist = paste0("(", unique(Conc.Units),
    ")/(", unique(Dose.Units), ")"), Rblood2plasma = "unitless ratio"),
  ...
)

Value

A `data.frame`with the following variables:

`param_name`: Character: Names of the model parameters
`param_units`: Character: Units of the model parameters
`optimize_param`: TRUE if each parameter is to be estimated from the data; FALSE otherwise
`use_param`: TRUE if each parameter is to be used in evaluating the model; FALSE otherwise
`lower_bounds`: Numeric: The lower bounds for each parameter
`upper_bounds`: Numeric: The upper bounds for each parameter
`start`: Numeric: The starting guesses for each parameter

Arguments

data: The data set to be fitted (e.g. the result of [preprocess_data()])
lower_bound: A mapping specified using a call to [alist()], giving the lower bounds for each variable, as expressions which may include variables in `data`.
upper_bound: A mapping specified using a call to [alist()], giving the upper bounds for each variable, as expressions which may include variables in `data`.
param_units: A mapping specified using a call to [alist()], giving the units for each variable, as expressions which may include variables in `data`.
...: Other parameters that can be specified in `pk_model`.

IV data, no oral data

If IV dosing data are available, but no oral dosing data are available, then only the parameter `Vdist` will be estimated from the data. The parameter `Fgutabs` cannot be estimated from IV data alone and will not be used to evaluate the model.

Oral data, no IV data

If oral dosing data are available, but no IV dosing data are available, then the parameters `Fgutabs` and `Vdist` cannot be identified separately. From oral data alone, only the ratio `Fgutabs/Vdist` can be identified. This ratio is represented by a single parameter named `Fgutabs_Vdist`. `Fgutabs` and `Vdist` will not be estimated nor used in model evaluation, but `Fgutabs_Vdist` will be estimated.

Oral data and IV data

If both oral and IV dosing data are available, then `Vdist` and `Fgutabs` will both be estimated from the data.

Blood and plasma data

If both blood and plasma data are available, then `Rblood2plasma` will be estimated from the data.

Only one of blood or plasma data

If only one of blood or plasma data are available, then `Rblood2plasma` will be held constant at 1, not estimated from the data.

Default lower and upper bounds for each parameter

Default lower and upper bounds for `Vdist`

By default, the lower bound for `Vdist` is 0.01, and the upper bound for `Vdist` is 100. These values were chosen based on professional judgment.

Default lower and upper bounds for `Fgutabs`

By default, the lower bound for `Fgutabs` is 0.0, and the upper bound for `Fgutabs` is 1. These are simply the bounds of the physically-meaningful range for a fraction.

Default lower and upper bounds for `Fgutabs_Vdist`

By default, the lower bound for the ratio `Fgutabs_Vdist` is 0.01, and the upper bound is 100. These values were chosen based on professional judgment.

Default lower and upper bounds for `Rblood2plasma`

By default, the lower bound for the blood:plasma partition coefficient `Rblood2plasma` is 0.01, and the upper bound is 100. These values were chosen based on professional judgment.

Starting values for each parameter

Starting values for each parameter (starting guesses for the numerical optimizer) are derived from the data using [get_starts_flat()].

If the starting values returned by [get_starts_flat()] fall outside the bounds for any parameter(s), then the starting value will be reset to a value halfway between the lower and upper bounds for that parameter.

Author

Caroline Ring, Gilberto Padilla Mercado