Package 'emaxnls'

Akaike information criterion / Bayesian information criterion

Description

Computes AIC or BIC for one or more fitted Emax models. Lower values indicate a better-fitting model; values are only meaningful in comparison to other models fitted to the same response variable and dataset.

Usage

## S3 method for class 'emaxlogistic'
AIC(object, ..., k = 2)

## S3 method for class 'emaxlogistic'
BIC(object, ...)

## S3 method for class 'emaxnls'
AIC(object, ..., k = 2)

## S3 method for class 'emaxnls'
BIC(object, ...)

Arguments

object	An emaxnls or emaxlogistic object
...	Optionally, more fitted model objects
k	Penalty per parameter in the AIC. The default is k = 2. Ignored for BIC(), which always uses log(n).

Details

AIC applies a penalty of 2 * k to minus twice the log-likelihood, where k is the number of estimated parameters. BIC applies log(n) * k, making it more conservative than AIC in large samples. When multiple models are passed, any non-converging models are dropped with a warning.

Value

If just one object is provided, a numeric value with the corresponding AIC (or BIC). If multiple objects are provided, a data.frame with rows corresponding to the objects and columns representing the number of parameters in the model (df) and the AIC or BIC.

Examples

mod_0 <- emax_nls(
  structural_model = rsp_1 ~ exp_1,
  covariate_model = list(E0 ~ 1, Emax ~ 1, logEC50 ~ 1),
  data = emax_df,
  opts = emax_nls_options(max_time = 10)
)
mod_1 <- emax_nls(
  structural_model = rsp_1 ~ exp_1,
  covariate_model = list(E0 ~ cnt_a, Emax ~ 1, logEC50 ~ 1),
  data = emax_df,
  opts = emax_nls_options(max_time = 10)
)

# calculate AIC for individual models
AIC(mod_0)
AIC(mod_1)

# calculate AIC for a sequence of models
AIC(mod_0, mod_1)

# calculate BIC for individual models
BIC(mod_0)
BIC(mod_1)

# calculate BIC for a sequence of models
BIC(mod_0, mod_1)

# emaxlogistic models
mod_b0 <- emax_logistic(
  structural_model = rsp_2 ~ exp_1,
  covariate_model = list(E0 ~ 1, Emax ~ 1, logEC50 ~ 1),
  data = emax_df,
  opts = emax_logistic_options(max_time = 10)
)
mod_b1 <- emax_logistic(
  structural_model = rsp_2 ~ exp_1,
  covariate_model = list(E0 ~ cnt_a, Emax ~ 1, logEC50 ~ 1),
  data = emax_df,
  opts = emax_logistic_options(max_time = 10)
)
AIC(mod_b0, mod_b1)
BIC(mod_b0, mod_b1)

---

Analysis of variance for Emax regression models

Description

Compares a sequence of nested Emax models. At least two model objects must be provided; all must be of the same class.

Usage

## S3 method for class 'emaxlogistic'
anova(object, ...)

## S3 method for class 'emaxnls'
anova(object, ...)

Arguments

object	An emaxnls or emaxlogistic object
...	Additional fitted model objects of the same class

Details

For emaxnls objects, calls stats::anova() on the underlying nls objects to produce an ANOVA table for the sequence of models. For emaxlogistic objects, computes a likelihood ratio chi-squared test comparing nested models; the test statistic is the difference in deviances and the reference distribution is chi-squared with degrees of freedom equal to the difference in the number of parameters. The nesting assumption is not checked; results are only interpretable when each successive model genuinely adds parameters to the previous one.

Value

For emaxnls objects, an analysis of variance table for a sequence of models. For emaxlogistic objects, a data frame with columns Df, Deviance, Df_diff, LRT, and ⁠Pr(>Chi)⁠.

Examples

mod_0 <- emax_nls(
  structural_model = rsp_1 ~ exp_1,
  covariate_model = list(E0 ~ 1, Emax ~ 1, logEC50 ~ 1),
  data = emax_df,
  opts = emax_nls_options(max_time = 10)
)
mod_1 <- emax_nls(
  structural_model = rsp_1 ~ exp_1,
  covariate_model = list(E0 ~ cnt_a, Emax ~ 1, logEC50 ~ 1),
  data = emax_df,
  opts = emax_nls_options(max_time = 10)
)
anova(mod_0, mod_1)

# emaxlogistic: likelihood ratio test
mod_b0 <- emax_logistic(
  structural_model = rsp_2 ~ exp_1,
  covariate_model = list(E0 ~ 1, Emax ~ 1, logEC50 ~ 1),
  data = emax_df,
  opts = emax_logistic_options(max_time = 10)
)
mod_b1 <- emax_logistic(
  structural_model = rsp_2 ~ exp_1,
  covariate_model = list(E0 ~ cnt_a, Emax ~ 1, logEC50 ~ 1),
  data = emax_df,
  opts = emax_logistic_options(max_time = 10)
)
anova(mod_b0, mod_b1)

---

Coefficients for an Emax regression

Description

Returns the named vector of fitted parameter values. Parameters involving a log transformation (logEC50, logHill) are returned on the log scale by default, which is the scale on which they are estimated.

Usage

## S3 method for class 'emaxnls'
coef(object, back_transform = FALSE, ...)

Arguments

object	An emaxnls or emaxlogistic object
back_transform	Should log-scaled parameters (logEC50, logHill) be back-transformed to original scale? The default is back_transform = FALSE.
...	Ignored

Details

Setting back_transform = TRUE exponentiates logEC50 and logHill and drops the log prefix from their names, expressing them on the concentration scale rather than the log-concentration scale on which they are estimated. confint() and vcov() are not affected by this argument and always return results on the log-concentration scale. The summary() method also accepts back_transform = TRUE and applies the same transformation to its coefficient table, including the confidence interval columns.

Value

A named numeric vector of parameter estimates

Examples

mod_c <- emax_nls(
  structural_model = rsp_1 ~ exp_1, 
  covariate_model = list(E0 ~ cnt_a, Emax ~ 1, logEC50 ~ 1), 
  data = emax_df,
  opts = emax_nls_options(max_time = 10)
)

# coefficients on the estimation scale
coef(mod_c)

# coefficients with log-scale parameters back-transformed
coef(mod_c, back_transform = TRUE)

mod_b <- emax_logistic(
  structural_model = rsp_2 ~ exp_1,
  covariate_model = list(E0 ~ cnt_a, Emax ~ 1, logEC50 ~ 1),
  data = emax_df,
  opts = emax_logistic_options(max_time = 10)
)
coef(mod_b)

---

Confidence intervals for Emax regression model parameters

Description

Computes profile likelihood confidence intervals for the model parameters. Profile likelihood intervals are generally preferred over Wald intervals in nonlinear settings because they do not assume the likelihood surface is quadratic near the estimates.

Usage

## S3 method for class 'emaxnls'
confint(
  object,
  parm = NULL,
  level = 0.95,
  back_transform = FALSE,
  simultaneous = FALSE,
  ...
)

Arguments

object	An emaxnls or emaxlogistic object
parm	A specification of which parameters are to be given confidence intervals, either a vector of numbers or a vector of names. If parm = NULL, all parameters are considered.
level	The confidence level required. The default is level = 0.95.
back_transform	Should log-scaled parameters (logEC50, logHill) be back-transformed to original scale? The default is back_transform = FALSE.
simultaneous	If TRUE, return simultaneous (joint) Wald confidence intervals rather than the default profile likelihood intervals. Defaults to FALSE.
...	Ignored

Details

By default, and when simultaneous = FALSE, this calls stats::confint.nls() for emaxnls objects. For emaxlogistic objects, the same profiling approach is applied to the final NLS fit from the IRLS algorithm at convergence. If profile likelihood computation fails (which can occur for sigmoidal models), a warning is issued and Wald intervals are returned instead.

When simultaneous = TRUE, a single critical value is derived from the joint multivariate normal distribution of the standardised parameter estimates (via mvtnorm::qmvnorm()). The resulting intervals have simultaneous coverage at level across all parameters and will be wider than the individual (pointwise) intervals. This matches the intervals produced by summary(object, simultaneous = TRUE).

Setting back_transform = TRUE exponentiates the confidence limits for logEC50 and logHill, expressing them on the concentration scale rather than the log-concentration scale on which they are estimated, and drops the log prefix from their row names.

Value

A matrix (or vector) with columns giving lower and upper confidence limits for each parameter. These will be labelled as (1-level)/2 and 1 - (1-level)/2 in % (by default 2.5% and 97.5%).

Examples

mod_c <- emax_nls(
  structural_model = rsp_1 ~ exp_1,
  covariate_model = list(E0 ~ cnt_a, Emax ~ 1, logEC50 ~ 1),
  data = emax_df,
  opts = emax_nls_options(max_time = 10)
)

# 95% confidence interval on the estimation scale
confint(mod_c)

# 90% confidence interval on the estimation scale
confint(mod_c, level = 0.9)

# 95% confidence interval with log-scale parameters back-transformed
confint(mod_c, back_transform = TRUE)

# simultaneous (joint) confidence intervals
confint(mod_c, simultaneous = TRUE)

mod_b <- emax_logistic(
  structural_model = rsp_2 ~ exp_1,
  covariate_model = list(E0 ~ cnt_a, Emax ~ 1, logEC50 ~ 1),
  data = emax_df,
  opts = emax_logistic_options(max_time = 10)
)
confint(mod_b)

---

Model deviance for an Emax regression model

Description

Returns a scalar measure of the overall lack of fit. The two model classes use different definitions of deviance that reflect their different likelihoods. Both measures decrease as the fit improves and are used internally by anova() for model comparison.

Usage

## S3 method for class 'emaxlogistic'
deviance(object, ...)

## S3 method for class 'emaxnls'
deviance(object, ...)

Arguments

object	An emaxnls or emaxlogistic object
...	Ignored

Value

A numeric scalar. For emaxnls objects, returns the residual sum of squares. For emaxlogistic objects, returns the binomial deviance (-2 * logLik).

Examples

# emaxnls deviance (residual sum of squares)
mod_c <- emax_nls(
  structural_model = rsp_1 ~ exp_1,
  covariate_model = list(E0 ~ cnt_a, Emax ~ 1, logEC50 ~ 1),
  data = emax_df,
  opts = emax_nls_options(max_time = 10)
)
deviance(mod_c)

# emaxlogistic deviance (binomial deviance)
mod_b <- emax_logistic(
  structural_model = rsp_2 ~ exp_1,
  covariate_model = list(E0 ~ cnt_a, Emax ~ 1, logEC50 ~ 1),
  data = emax_df,
  opts = emax_logistic_options(max_time = 10)
)
deviance(mod_b)

---

Residual degrees of freedom for an Emax regression model

Description

Returns the residual degrees of freedom, equal to the number of observations minus the number of estimated parameters.

Usage

## S3 method for class 'emaxlogistic'
df.residual(object, ...)

## S3 method for class 'emaxnls'
df.residual(object, ...)

Arguments

object	An emaxnls or emaxlogistic object
...	Ignored

Details

For emaxnls objects, the value is obtained directly from the underlying nls fit. For emaxlogistic objects, it is computed as nobs(object) - length(coef(object)).

Value

A numeric scalar

Examples

mod_c <- emax_nls(
  structural_model = rsp_1 ~ exp_1,
  covariate_model = list(E0 ~ cnt_a, Emax ~ 1, logEC50 ~ 1),
  data = emax_df,
  opts = emax_nls_options(max_time = 10)
)
df.residual(mod_c)

mod_b <- emax_logistic(
  structural_model = rsp_2 ~ exp_1,
  covariate_model = list(E0 ~ cnt_a, Emax ~ 1, logEC50 ~ 1),
  data = emax_df,
  opts = emax_logistic_options(max_time = 10)
)
df.residual(mod_b)

---

Check Emax regression model for convergence status

Description

Returns TRUE if the model converged during fitting and FALSE otherwise. The reason for convergence or non-convergence is attached as the names attribute of the return value, so it prints alongside the logical result.

Usage

emax_converged(mod)

Arguments

mod	An emaxnls object

Value

A named logical scalar. The value is TRUE when the model converged and FALSE otherwise. The names attribute holds a short description of the outcome:

• "converged": the optimiser reached a solution successfully.

• "maximum time exceeded": the max_time limit set in emax_nls_options() / emax_logistic_options() was hit before the optimiser finished.

• "maximum iterations exceeded": the optimiser ran out of iterations. This applies to the Gauss-Newton algorithm (when stats::nls() reports "number of iterations exceeded maximum") and to the Levenberg-Marquardt algorithm (when minpack.lm::nlsLM() reports that the iteration count has reached maxiter). The iteration budget can be increased via the optim_control argument of emax_nls_options().

• Raw optimiser message: all other failures return the error message from the underlying optimiser directly. Common examples include a singular gradient matrix at the initial parameter estimates, the Gauss-Newton step factor collapsing below minFactor, and Port-algorithm convergence codes such as false convergence (code 8) or singular convergence (code 7). These messages are algorithm-specific and are passed through unchanged because no single label covers them accurately.

See Also

emax_nls(), emax_nls_options()

---

Sample simulated data for Emax exposure-response models with covariates.

Description

Sample simulated data for Emax exposure-response models with covariates.

Usage

emax_df

Format

A data frame with columns:

id

Identifier column

dose

Nominal dose, units not specified

exp_1

Exposure value, units and metric not specified

exp_2

Exposure value, units and metric not specified, but different from exp_1

rsp_1

Continuous response value (units not specified)

rsp_2

Binary response value (group labels not specified)

cnt_a

Continuous valued covariate

cnt_b

Continuous valued covariate

cnt_c

Continuous valued covariate

bin_d

Binary valued covariate

bin_e

Binary valued covariate

cat_f

Categorical covariate

Details

This simulated dataset is entirely synthetic. It is a generic data set that can be used to illustrate Emax modelling. It contains variables corresponding to dose and exposure, and includes both a continuous response variable and a binary response variable. Three continuous valued covariates are included, along with two binary covariates.

You can find the data generating code in the package source code, under R/data.R

Examples

emax_df

---

Construct Emax prediction function from model object

Description

Extracts a customizable prediction function from a fitted Emax model, allowing predictions to be evaluated at arbitrary data and parameter values.

Usage

emax_fun(mod, ...)

## S3 method for class 'emaxlogistic'
emax_fun(mod, ...)

## S3 method for class 'emaxnls'
emax_fun(mod, ...)

Arguments

mod	An emaxnls or emaxlogistic object
...	Ignored

Details

The extracted function accepts data and param arguments. Both default to the values used when fitting the model. When supplying custom values, data must contain all variables used by the model, and param must be a named numeric vector whose names exactly match those returned by coef(mod).

Scale of predictions. For emaxnls objects the returned function produces predictions on the response scale (the same scale as the outcome variable). For emaxlogistic objects the structural Emax model is parameterized on the logit scale — logit(p) = E0 + Emax * x / (x + EC50) — but emax_fun() applies the inverse-logit transformation before returning, so predictions are on the probability scale. This is consistent with the default behaviour of fitted() and predict() for emaxlogistic objects. If you need the linear predictor (logit scale) directly, use fitted(object, type = "link") or predict(object, type = "link").

Value

A function with arguments param and data that evaluates the Emax model at the supplied (or default) parameter values and data. For emaxnls objects the return values are on the response scale; for emaxlogistic objects they are predicted probabilities in $(0, 1)$.

See Also

emax_nls(), emax_logistic()

Examples

mod_c <- emax_nls(
  structural_model = rsp_1 ~ exp_1, 
  covariate_model = list(E0 ~ cnt_a, Emax ~ 1, logEC50 ~ 1), 
  data = emax_df,
  opts = emax_nls_options(max_time = 10)
)

if (emax_converged(mod_c)) {

  par <- coef(mod_c)
  mod_fn <- emax_fun(mod_c)
  
  # apply the function to a few rows of the original data
  mod_fn(data = emax_df[120:125, ], param = par)
  
  # adjust the parameters and re-evaluate
  new_par <- par
  new_par["E0_Intercept"] <- 0
  mod_fn(data = emax_df[120:125, ], param = new_par)

}

# for emaxlogistic, the returned function gives probabilities
mod_b <- emax_logistic(
  structural_model = rsp_2 ~ exp_1,
  covariate_model = list(E0 ~ cnt_a, Emax ~ 1, logEC50 ~ 1),
  data = emax_df,
  opts = emax_logistic_options(max_time = 10)
)

if (emax_converged(mod_b)) {
  mod_fn_b <- emax_fun(mod_b)
  mod_fn_b(data = emax_df[120:125, ])
}

---

Estimate parameters for a logistic Emax regression model

Description

Fits a logistic Emax regression model for a binary response variable using iterative reweighted least squares (IRLS). For continuous outcomes, use emax_nls() instead.

Usage

emax_logistic(
  structural_model,
  covariate_model = NULL,
  data,
  init = NULL,
  opts = NULL
)

Arguments

structural_model	A two-sided formula of the form response ~ exposure
covariate_model	A list of two-sided formulas, each specifying a covariate model for a structural parameter. When NULL (the default), an intercept-only hyperbolic Emax model is fitted — equivalent to list(E0 ~ 1, Emax ~ 1, logEC50 ~ 1).
data	A data frame that includes all relevant variables
init	Initial values and bounds for parameters. See emax_logistic_init()
opts	Model fitting and optimisation options. See emax_logistic_options()

Details

The structural Emax model is placed on the log-odds (logit) scale:

logit(p) = E0 + Emax * x / (x + EC50) (hyperbolic)

logit(p) = E0 + Emax * x^h / (x^h + EC50^h) (sigmoidal)

Estimation uses iterative reweighted least squares (IRLS). At each outer iteration a weighted NLS problem is solved using working weights and a working response derived from the current parameter estimates. This is equivalent to Fisher scoring and produces maximum likelihood estimates at convergence.

The interface mirrors the emax_nls() function for continuous response models: the structural_model and covariate_model arguments have the same specification, including support for sigmoidal models via a logHill term. The response variable in structural_model must be a binary (0/1) numeric vector.

Value

An object of class emaxlogistic (which also inherits from emaxnls)

See Also

emax_logistic_options(), emax_logistic_init(), emax_nls()

Examples

# simplest call: hyperbolic Emax with no covariates
emax_logistic(
  structural_model = rsp_2 ~ exp_1,
  data = emax_df,
  opts = emax_logistic_options(max_time = 10)
)

# with a covariate on the baseline parameter
emax_logistic(
  structural_model = rsp_2 ~ exp_1,
  covariate_model = list(E0 ~ cnt_a, Emax ~ 1, logEC50 ~ 1),
  data = emax_df,
  opts = emax_logistic_options(max_time = 10)
)

---

Construct an initial guess for logistic Emax model parameters

Description

Constructs a data frame of starting values and parameter bounds for the logistic Emax model, using the same heuristic approach as emax_nls_init() applied to the empirical logit scale rather than the raw response.

Usage

emax_logistic_init(structural_model, covariate_model = NULL, data)

Arguments

structural_model	A two-sided formula of the form response ~ exposure
covariate_model	A list of two-sided formulas, each specifying a covariate model for a structural parameter. When NULL (the default), an intercept-only hyperbolic Emax model is assumed — equivalent to list(E0 ~ 1, Emax ~ 1, logEC50 ~ 1).
data	A data frame

Value

A data frame with columns parameter, covariate, start, lower, and upper

See Also

emax_logistic(), emax_logistic_options()

Examples

# intercept-only hyperbolic Emax (default covariate_model)
emax_logistic_init(
  structural_model = rsp_2 ~ exp_1,
  data = emax_df
)

# with a covariate on E0
emax_logistic_init(
  structural_model = rsp_2 ~ exp_1,
  covariate_model = list(E0 ~ cnt_a, Emax ~ 1, logEC50 ~ 1),
  data = emax_df
)

---

Settings used to estimate a logistic Emax model

Description

Constructs a settings object controlling the NLS optimiser and IRLS convergence for emax_logistic(). Pass the result to the opts argument of emax_logistic().

Usage

emax_logistic_options(
  optim_method = "gauss",
  optim_control = NULL,
  quiet = FALSE,
  na.action = getOption("na.action"),
  max_iter = 25,
  tol = 1e-06,
  max_time = Inf
)

Arguments

optim_method	Character string specifying the algorithm used for the weighted NLS step within each IRLS iteration. Supported options are "gauss" (default), "port", and "levenberg". See emax_nls_options() for details on each.
optim_control	A list of arguments controlling the NLS optimiser. The default is optim_control = NULL, which uses the default settings for the relevant optimisation function.
quiet	When TRUE, convergence warnings are suppressed.
na.action	How should missing values in the data be handled? The default is na.action = getOption("na.action").
max_iter	Maximum number of IRLS outer iterations (default 25).
tol	Convergence tolerance: IRLS stops when the change in binomial deviance between successive iterations falls below tol (default 1e-6).
max_time	Maximum elapsed time in seconds allowed for the entire model fit (including all IRLS iterations). If the optimiser has not converged within this time, it is terminated and the model is treated as non-converged. Defaults to Inf (no time limit).

Value

A list of settings

See Also

emax_logistic(), emax_logistic_init()

Examples

# default options
emax_logistic_options()

# increase maximum IRLS iterations
emax_logistic_options(max_iter = 50)

---

Estimate parameters for an Emax regression model

Description

Fits an Emax regression model for a continuous response variable using nonlinear least squares. For binary outcomes, use emax_logistic() instead.

Usage

emax_nls(
  structural_model,
  covariate_model = NULL,
  data,
  init = NULL,
  opts = NULL
)

Arguments

structural_model	A two-sided formula of the form response ~ exposure
covariate_model	A list of two-sided formulas, each specifying a covariate model for a structural parameter. When NULL (the default), an intercept-only hyperbolic Emax model is fitted — equivalent to list(E0 ~ 1, Emax ~ 1, logEC50 ~ 1).
data	A data frame that includes all relevant variables
init	Initial values and bounds for parameters. See emax_nls_init()
opts	Model fitting and optimisation options. See emax_nls_options()

Details

Pass a two-sided formula to structural_model to specify the response and exposure variables (e.g., response ~ exposure), and a list of formulas to covariate_model to specify covariates. At a minimum the covariate model requires formulas for E0, Emax, and logEC50. A formula like E0 ~ age + group includes age and group as covariates on the baseline response; use Emax ~ 1 when no covariates are to be added for a parameter.

To fit a sigmoidal Emax model (estimating the Hill parameter), include a formula for logHill in covariate_model, e.g. logHill ~ 1. Without this term a hyperbolic model is fitted. Interaction terms in the covariate model are not currently supported.

Starting values are constructed automatically via emax_nls_init() unless the init argument is supplied manually. Three optimisation algorithms are available; see emax_nls_options() for details.

Value

An object of class emaxnls

See Also

emax_nls_options(), emax_nls_init()

Examples

# simplest call: hyperbolic Emax with no covariates
emax_nls(
  structural_model = rsp_1 ~ exp_1,
  data = emax_df,
  opts = emax_nls_options(max_time = 10)
)

# with a covariate on the baseline parameter
emax_nls(
  structural_model = rsp_1 ~ exp_1, 
  covariate_model = list(E0 ~ cnt_a, Emax ~ 1, logEC50 ~ 1), 
  data = emax_df,
  opts = emax_nls_options(max_time = 10)
)

---

Construct an initial guess for the Emax model parameters

Description

Constructs a data frame of starting values and parameter bounds for the Emax NLS optimisation, using heuristics derived from the data.

Usage

emax_nls_init(structural_model, covariate_model = NULL, data)

Arguments

structural_model	A two-sided formula of the form response ~ exposure
covariate_model	A list of two-sided formulas, each specifying a covariate model for a structural parameter. When NULL (the default), an intercept-only hyperbolic Emax model is assumed — equivalent to list(E0 ~ 1, Emax ~ 1, logEC50 ~ 1).
data	A data frame

Details

The emax_nls() function requires that the user specify the initial values for the model parameters. Specifically, it expects to be supplied with a data frame with columns named parameter, covariate, and start. If a bounded optimisation method is used (e.g. if the "port" method is used), the data frame also needs to have columns named lower and upper. The data frame should contain one row per parameter. In most cases the user does not need to define this manually, because emax_nls_init() can use heuristics to make a sensible guess about what to use as starting values. By default this is what emax_nls() relies upon, automatically calling emax_nls_init() using the appropriate values for the structural_model, the covariate_model, and the data.

Value

A data frame

See Also

emax_nls(), emax_nls_options()

Examples

# intercept-only hyperbolic Emax (default covariate_model)
emax_nls_init(
  structural_model = rsp_1 ~ exp_1,
  data = emax_df
)

# with a covariate on E0
emax_nls_init(
  structural_model = rsp_1 ~ exp_1, 
  covariate_model = list(E0 ~ cnt_a, Emax ~ 1, logEC50 ~ 1), 
  data = emax_df
)

# compare to the values estimated:
coef(emax_nls(
  structural_model = rsp_1 ~ exp_1, 
  covariate_model = list(E0 ~ cnt_a, Emax ~ 1, logEC50 ~ 1), 
  data = emax_df,
  opts = emax_nls_options(max_time = 10)
))

---

Settings used to estimate Emax model

Description

Constructs a settings object controlling the optimisation algorithm and other aspects of model fitting for emax_nls(). Pass the result to the opts argument of emax_nls().

Usage

emax_nls_options(
  optim_method = "gauss",
  optim_control = NULL,
  quiet = FALSE,
  weights = NULL,
  na.action = getOption("na.action"),
  max_time = Inf
)

Arguments

optim_method	Character string specifying the algorithm used to solve the nonlinear least squares optimisation problem. Supported options are "gauss" (the default), "port", and "levenberg". See details.
optim_control	A list of arguments used to control the behaviour of the optimisation algorithm. Allowed values differ depending on which algorithm is used. The default is optim_control = NULL, which uses the default settings for the relevant optimisation function; see details.
quiet	When quiet=TRUE, messages are suppressed
weights	Numeric vector providing the weights for observations. When specified, weighted least squares is used. The default is weights = NULL (unweighted least squares).
na.action	How should missing values in the data be handled? The default is na.action = getOption("na.action").
max_time	Maximum elapsed time in seconds allowed for the model fit. If the optimiser has not converged within this time, it is terminated and the model is treated as non-converged (the same outcome as any other convergence failure). Defaults to Inf (no time limit).

Details

At present there are three supported values for optim_method:

• "gauss": Estimate parameters using the Gauss-Newton algorithm. This is equivalent to the using "default" option in stats::nls()

• "port": Estimate parameters using bounded optimisation with the "nl2sol" algorithm from from the the Port library. Equivalent to "port" in stats::nls()

• "levenberg": Estimate parameters using the Levenberg-Marquardt algorithm. This is equivalent to using minpack.lm::nlsLM() from the "minpack.lm" package.

Note that the Golub-Pereyra algorithm for partially linear least-squares (i.e. the "plinear" option in stats::nls()) is not currently supported for Emax regression. Informal testing suggests it does not perform well for these models, and rarely converges.

The optim_control argument mirrors the corresponding control arguments for the respective optimisation methods:

• For "gauss" and "port": the list should match the output of stats::nls.control()

• For "levenberg": the list should match the output of minpack.lm::nls.lm.control()

If optim_control = NULL, the default settings are used for the relevant function.

Value

A list of settings

See Also

emax_nls(), emax_nls_init()

Examples

# default options
emax_nls_options()

# switch to levenberg-marquardt
if (require("minpack.lm", quietly = TRUE)) emax_nls_options(optim_method = "levenberg")

---

Stepwise covariate modelling for Emax regression

Description

Performs stepwise covariate modelling by forward addition (emax_scm_forward()), backward elimination (emax_scm_backward()), or both in sequence. Use emax_scm_history() to retrieve the history of all models tested during the procedure.

Usage

emax_scm_forward(
  mod,
  candidates,
  threshold = 0.01,
  criterion = "p-value",
  seed = NULL
)

emax_scm_backward(
  mod,
  candidates,
  threshold = 0.001,
  criterion = "p-value",
  seed = NULL
)

emax_scm_history(mod)

Arguments

mod	An emaxnls object
candidates	A list of candidate covariates
threshold	Threshold for addition or removal. Used only when criterion = "p-value" (the default); ignored otherwise.
criterion	Model selection criterion. One of "p-value" (default), "aic", or "bic".
seed	Seed for the RNG state

Details

The candidates argument must be a named list whose names correspond to structural parameters (e.g. E0, Emax) and whose values are character vectors of covariate names to consider. See the examples for an illustration.

Three model selection criteria are available via the criterion argument:

• "p-value" (default): a term is added if its ANOVA p-value falls below threshold (forward) or removed if its p-value exceeds threshold (backward). When multiple candidates satisfy the threshold, the one with the most extreme p-value is chosen.

• "aic": a term is added (forward) or removed (backward) if doing so strictly decreases AIC. When multiple candidates improve AIC, the one yielding the lowest AIC is chosen.

• "bic": same as "aic" but using BIC as the criterion.

When criterion is "aic" or "bic", the threshold argument has no effect and is ignored.

The history returned by emax_scm_history() always records AIC and BIC for every model tested (columns model_aic and model_bic), regardless of which criterion was used for selection. The criterion column records which criterion drove each forward or backward step.

The seed argument controls the RNG state for any stochastic components of the procedure. It is currently experimental and may be removed in future releases.

Every model tested during the procedure is stored internally in the returned object. Use emax_scm_history() to extract this record.

Value

An object of class emaxnls

See Also

emax_nls()

Examples

base_model <- emax_nls(
  structural_model = rsp_1 ~ exp_1,
  data = emax_df,
  opts = emax_nls_options(max_time = 10)
)

covariate_list <- list(
  E0 = c("cnt_a", "cnt_b", "cnt_c", "bin_d", "bin_e"),
  Emax = c("cnt_a", "cnt_b", "cnt_c", "bin_d", "bin_e")
)

# add covariates to the base model using forward addition (p-value criterion)
forward_model <- emax_scm_forward(
  mod = base_model,
  candidates = covariate_list, 
  threshold = .01
)
forward_model

# remove covariates from the forward model using backward deletion
final_model <- emax_scm_backward(
  mod = forward_model,
  candidates = covariate_list, 
  threshold = .001
) 
final_model

# show the history of all models tested, including which criterion was used
emax_scm_history(final_model)

# AIC-based forward addition
forward_aic <- emax_scm_forward(
  mod = base_model,
  candidates = covariate_list,
  criterion = "aic"
)

# BIC-based backward elimination
final_bic <- emax_scm_backward(
  mod = forward_aic,
  candidates = covariate_list,
  criterion = "bic"
)

emax_scm_history(final_bic)

# example using binary outcomes
base_model_logistic <- emax_logistic(
  structural_model = rsp_2 ~ exp_1,
  data = emax_df,
  opts = emax_logistic_options(max_time = 10)
)
forward_model_logistic <- emax_scm_forward(
  mod = base_model_logistic,
  candidates = covariate_list, 
  threshold = .01
)
final_model_logistic <- emax_scm_backward(
  mod = forward_model_logistic,
  candidates = covariate_list, 
  threshold = .001
)

final_model_logistic

emax_scm_history(final_model_logistic)

---

Add or remove a covariate term from an Emax regression

Description

Add or remove a single covariate term from an existing Emax regression model, returning a new fitted model object.

Usage

emax_add_term(mod, formula)

emax_remove_term(mod, formula)

Arguments

mod	An emaxnls object
formula	A formula such as E0 ~ AGE

Details

These functions are not typically called directly; they underpin the stepwise covariate modelling procedures that are very commonly used when building Emax regressions.

Value

An object of class emaxnls

See Also

emax_nls(), emax_scm

Examples

opts <- emax_nls_options(max_time = 10)
mod_0 <- emax_nls(rsp_1 ~ exp_1, list(E0 ~ 1, Emax ~ 1, logEC50 ~ 1), emax_df, opts = opts)
mod_1 <- emax_nls(rsp_1 ~ exp_1, list(E0 ~ cnt_a, Emax ~ 1, logEC50 ~ 1), emax_df, opts = opts)

if (emax_converged(mod_0)) emax_add_term(mod_0, E0 ~ cnt_a)

if (emax_converged(mod_1)) emax_remove_term(mod_1, E0 ~ cnt_a)

---

Fitted values for an Emax regression model

Description

Returns the model predictions at the original data points. For emaxlogistic objects, the type argument controls whether fitted probabilities or the linear predictor on the logit scale are returned.

Usage

## S3 method for class 'emaxlogistic'
fitted(object, type = c("response", "link"), ...)

## S3 method for class 'emaxnls'
fitted(object, ...)

Arguments

object	An emaxnls or emaxlogistic object
type	For emaxlogistic objects: "response" (default) returns fitted probabilities; "link" returns the linear predictor on the logit scale. Ignored for emaxnls objects.
...	Ignored

Details

For emaxnls objects, these are the predicted values from the Emax curve evaluated at each observation's exposure and covariate values.

Value

A numeric vector of fitted values, with length equal to the number of observations in the original data

Examples

mod_c <- emax_nls(
  structural_model = rsp_1 ~ exp_1,
  covariate_model = list(E0 ~ cnt_a, Emax ~ 1, logEC50 ~ 1),
  data = emax_df,
  opts = emax_nls_options(max_time = 10)
)
fitted(mod_c)[1:20]

mod_b <- emax_logistic(
  structural_model = rsp_2 ~ exp_1,
  covariate_model = list(E0 ~ cnt_a, Emax ~ 1, logEC50 ~ 1),
  data = emax_df,
  opts = emax_logistic_options(max_time = 10)
)
fitted(mod_b)[1:20]
fitted(mod_b, type = "link")[1:20]

---

Log-likelihood for an Emax regression model

Description

Evaluates the log-likelihood of a fitted Emax model at the maximum likelihood estimates. The returned object is compatible with AIC(), BIC(), and likelihood ratio tests via anova().

Usage

## S3 method for class 'emaxlogistic'
logLik(object, REML = FALSE, ...)

## S3 method for class 'emaxnls'
logLik(object, REML = FALSE, ...)

Arguments

object	An emaxnls or emaxlogistic object
REML	For emaxnls objects only REML = FALSE is supported. Ignored for emaxlogistic objects.
...	Ignored

Details

For emaxnls objects, the log-likelihood is computed under the assumption of normally distributed errors, as returned by stats::logLik.nls(). For emaxlogistic objects, it is the binomial log-likelihood evaluated at the fitted probabilities. The logLik object carries df (number of parameters) and nobs attributes.

Value

An object of class logLik with at least one attribute, "df" (degrees of freedom), giving the number of estimated parameters in the model.

Examples

mod_c <- emax_nls(
  structural_model = rsp_1 ~ exp_1,
  covariate_model = list(E0 ~ cnt_a, Emax ~ 1, logEC50 ~ 1),
  data = emax_df,
  opts = emax_nls_options(max_time = 10)
)
logLik(mod_c)

mod_b <- emax_logistic(
  structural_model = rsp_2 ~ exp_1,
  covariate_model = list(E0 ~ cnt_a, Emax ~ 1, logEC50 ~ 1),
  data = emax_df,
  opts = emax_logistic_options(max_time = 10)
)
logLik(mod_b)

---

Number of observations for an Emax regression model

Description

Returns the number of observations used when fitting the model.

Usage

## S3 method for class 'emaxnls'
nobs(object, ...)

Arguments

object	An emaxnls or emaxlogistic object
...	Ignored

Details

This reflects the actual number of rows passed to the fitting algorithm after any missing-value handling specified via the na.action option in emax_nls_options() or emax_logistic_options(). The value is used internally by BIC() and df.residual().

Value

A numeric scalar

Examples

mod_c <- emax_nls(
  structural_model = rsp_1 ~ exp_1,
  covariate_model = list(E0 ~ cnt_a, Emax ~ 1, logEC50 ~ 1),
  data = emax_df,
  opts = emax_nls_options(max_time = 10)
)
nobs(mod_c)

mod_b <- emax_logistic(
  structural_model = rsp_2 ~ exp_1,
  covariate_model = list(E0 ~ cnt_a, Emax ~ 1, logEC50 ~ 1),
  data = emax_df,
  opts = emax_logistic_options(max_time = 10)
)
nobs(mod_b)

---

Predicting from Emax regression models

Description

Generates predictions from a fitted Emax model, either at the original data points or at new covariate and exposure values supplied via newdata. Standard errors and confidence or prediction intervals can be requested.

Usage

## S3 method for class 'emaxlogistic'
predict(
  object,
  newdata = NULL,
  type = c("response", "link"),
  se.fit = FALSE,
  interval = "none",
  level = 0.95,
  ...
)

## S3 method for class 'emaxnls'
predict(
  object,
  newdata = NULL,
  se.fit = FALSE,
  interval = "none",
  level = 0.95,
  ...
)

Arguments

object	An emaxnls or emaxlogistic object
newdata	A named list or data frame in which to look for variables with which to predict. If newdata is missing the fitted values at the original data points are returned.
type	For emaxlogistic objects: "response" (default) returns predicted probabilities; "link" returns the linear predictor on the logit scale. Ignored for emaxnls objects.
se.fit	A switch indicating if standard errors are required. The default is se.fit = FALSE.
interval	A character string indicating if prediction intervals or a confidence interval on the mean responses are to be calculated. Can be "none" (the default), "confidence", or "prediction".
level	A numeric scalar between 0 and 1 giving the confidence level for the intervals (if any) to be calculated. The default is level = 0.95.
...	Ignored

Details

For emaxlogistic objects, when interval is set, the bounds are first computed on the link scale and then passed through the inverse logit transformation, ensuring they remain in the unit interval on the probability scale.

Value

The return value differs slightly depending on inputs. When se.fit = FALSE, it produces a vector or matrix of predictions with column names fit, lwr and upr if the interval argument is set. When se.fit = TRUE, it returns a list with the following components:

• fit: vector or matrix as above

• se.fit: standard error of the predicted means

• residual.scale: residual standard deviation

• df: residual degrees of freedom

Examples

mod_c <- emax_nls(
  structural_model = rsp_1 ~ exp_1,
  covariate_model = list(E0 ~ cnt_a, Emax ~ 1, logEC50 ~ 1),
  data = emax_df,
  opts = emax_nls_options(max_time = 10)
)

# return a vector of predictions
predict(mod_c)[1:20]

# return a matrix with confidence intervals
predict(mod_c, interval = "confidence", se.fit = FALSE)

# emaxlogistic predicted probabilities
mod_b <- emax_logistic(
  structural_model = rsp_2 ~ exp_1,
  covariate_model = list(E0 ~ cnt_a, Emax ~ 1, logEC50 ~ 1),
  data = emax_df,
  opts = emax_logistic_options(max_time = 10)
)
predict(mod_b)[1:20]
predict(mod_b, type = "link")[1:20]

---

Print an Emax regression model object

Description

The print() method for emaxnls and emaxlogistic objects provides a concise model overview: the structural and covariate formulas, key fit statistics, and a coefficient table showing estimates and confidence intervals. Hypothesis tests are deliberately omitted from the printed output; use summary() for inferential results.

Usage

## S3 method for class 'emaxlogistic'
print(x, conf_level = 0.95, ...)

## S3 method for class 'emaxnls'
print(x, conf_level = 0.95, ...)

Arguments

x	An emaxnls or emaxlogistic object
conf_level	Confidence level for the coefficient intervals shown in the printed table. Defaults to 0.95.
...	Ignored

Value

Invisibly returns the original object

Examples

mod_c <- emax_nls(
  structural_model = rsp_1 ~ exp_1,
  covariate_model = list(E0 ~ cnt_a, Emax ~ 1, logEC50 ~ 1),
  data = emax_df,
  opts = emax_nls_options(max_time = 10)
)
print(mod_c)

mod_b <- emax_logistic(
  structural_model = rsp_2 ~ exp_1,
  covariate_model = list(E0 ~ cnt_a, Emax ~ 1, logEC50 ~ 1),
  data = emax_df,
  opts = emax_logistic_options(max_time = 10)
)
print(mod_b)

---

Residuals for an Emax regression model

Description

For emaxnls objects, returns raw residuals on the response scale. For emaxlogistic objects, Pearson or deviance residuals are available via the type argument.

Usage

## S3 method for class 'emaxlogistic'
residuals(object, type = c("pearson", "deviance"), ...)

## S3 method for class 'emaxnls'
residuals(object, ...)

Arguments

object	An emaxnls or emaxlogistic object
type	For emaxlogistic objects: the type of residuals to return. "pearson" (default) returns Pearson residuals; "deviance" returns deviance residuals. Ignored for emaxnls objects.
...	Ignored

Details

Pearson residuals are the raw residuals divided by sqrt(mu * (1 - mu)), the estimated standard deviation of a Bernoulli observation, giving a standardised measure of discrepancy. Deviance residuals are the signed square root of each observation's contribution to the total binomial deviance; their sum of squares equals the model deviance returned by deviance().

Value

A numeric vector of residuals

Examples

mod_c <- emax_nls(
  structural_model = rsp_1 ~ exp_1,
  covariate_model = list(E0 ~ cnt_a, Emax ~ 1, logEC50 ~ 1),
  data = emax_df,
  opts = emax_nls_options(max_time = 10)
)
residuals(mod_c)[1:20]

mod_b <- emax_logistic(
  structural_model = rsp_2 ~ exp_1,
  covariate_model = list(E0 ~ cnt_a, Emax ~ 1, logEC50 ~ 1),
  data = emax_df,
  opts = emax_logistic_options(max_time = 10)
)
residuals(mod_b)[1:20]
residuals(mod_b, type = "deviance")[1:20]

---

Residual standard deviation for an Emax regression model

Description

Returns the estimated residual standard deviation from the NLS fit. This method is only available for emaxnls objects; there is no analogous quantity for emaxlogistic models.

Usage

## S3 method for class 'emaxnls'
sigma(object, ...)

Arguments

object	An emaxnls object
...	Ignored

Details

Under the assumption of normally distributed errors, sigma estimates the standard deviation of the error term in the Emax model. It is computed as the square root of the residual sum of squares divided by the residual degrees of freedom.

Value

A numeric scalar

Examples

mod <- emax_nls(
  structural_model = rsp_1 ~ exp_1, 
  covariate_model = list(E0 ~ cnt_a, Emax ~ 1, logEC50 ~ 1), 
  data = emax_df,
  opts = emax_nls_options(max_time = 10)
)
sigma(mod)

---

Simulate responses from an Emax regression model

Description

Generates simulated response datasets from a fitted Emax model, propagating uncertainty in the parameter estimates. This is useful for constructing simulation-based confidence bands, for predictive checks, or for bootstrapping downstream analyses.

Usage

## S3 method for class 'emaxlogistic'
simulate(object, nsim = 1, seed = NULL, ...)

## S3 method for class 'emaxnls'
simulate(object, nsim = 1, seed = NULL, ...)

Arguments

object	An emaxnls or emaxlogistic object
nsim	Number of replicates. The default is nsim = 1.
seed	Used to set RNG seed. The default is seed = NULL, which does not set the seed.
...	Ignored

Details

The simulate() method samples new parameter values from the multivariate normal distribution implied by the estimated covariance matrix, then simulates responses at those parameter values using mvtnorm::rmvnorm(). For emaxlogistic objects, predicted probabilities are computed from each parameter draw and binary outcomes are drawn from Bernoulli(p) for each observation.

Value

A data frame with nsim columns named sim_1, sim_2, etc.

Examples

mod_c <- emax_nls(
  structural_model = rsp_1 ~ exp_1,
  covariate_model = list(E0 ~ cnt_a, Emax ~ 1, logEC50 ~ 1),
  data = emax_df,
  opts = emax_nls_options(max_time = 10)
)
simulate(mod_c)

mod_b <- emax_logistic(
  structural_model = rsp_2 ~ exp_1,
  covariate_model = list(E0 ~ cnt_a, Emax ~ 1, logEC50 ~ 1),
  data = emax_df,
  opts = emax_logistic_options(max_time = 10)
)
simulate(mod_b)

---

Summary of an Emax regression model

Description

Returns a tidy coefficient table for a fitted emaxnls or emaxlogistic model, combining parameter estimates, standard errors, test statistics, p-values, and confidence intervals.

Usage

## S3 method for class 'emaxlogistic'
summary(
  object,
  conf_level = 0.95,
  back_transform = FALSE,
  p_adjust = "none",
  simultaneous = FALSE,
  suppress_nonsensical = TRUE,
  ...
)

## S3 method for class 'emaxnls'
summary(
  object,
  conf_level = 0.95,
  back_transform = FALSE,
  p_adjust = "none",
  simultaneous = FALSE,
  suppress_nonsensical = TRUE,
  ...
)

Arguments

object	An emaxnls or emaxlogistic object
conf_level	Confidence level for interval estimates. Defaults to 0.95.
back_transform	Should logEC50 and logHill parameters be back-transformed to the concentration scale? If TRUE, these parameters are exponentiated and renamed to EC50 and Hill respectively, and their confidence intervals are transformed accordingly. Standard errors and test statistics on the back-transformed scale are not available and are set to NA.
p_adjust	Method for adjusting p-values for multiple comparisons, passed to stats::p.adjust(). Defaults to "none". Parameters with suppressed p-values (see suppress_nonsensical) are excluded from the adjustment set. This affects only the p_value column and is independent of simultaneous; see the "Multiplicity: p-value adjustment versus simultaneous intervals" section below.
simultaneous	If TRUE, compute simultaneous (joint) confidence intervals using the multivariate normal distribution via mvtnorm::qmvnorm(). This gives wider intervals that provide joint coverage at conf_level across all parameters simultaneously. Defaults to FALSE. This affects only the confidence-interval columns and is independent of p_adjust; see the "Multiplicity: p-value adjustment versus simultaneous intervals" section below.
suppress_nonsensical	If TRUE (the default), suppress the test statistic and p-value for logEC50_Intercept. The logEC50 intercept is estimated on the log-concentration scale, and testing H0: logEC50 = 0 is equivalent to testing whether EC50 equals 1 on the concentration scale — a threshold with no general pharmacometric meaning. The confidence interval for logEC50 is always reported regardless of this setting. Pass suppress_nonsensical = FALSE to restore the raw test results.
...	Ignored

Details

Which tests are reported by default

Most parameters have a meaningful point null at zero:

• Emax_Intercept: tests whether any exposure-response relationship exists.

• logHill_Intercept: tests whether logHill = 0, i.e., whether the Hill parameter equals 1 on the concentration scale, which would mean the sigmoidal model reduces to a hyperbolic one.

• E0_Intercept: tests whether the baseline response is zero. This is informative when the outcome is expressed as change from baseline, a common convention in pharmacometrics.

• Covariate beta terms: test whether a given covariate has any effect on the corresponding structural parameter.

The one exception is logEC50_Intercept. The model is parameterized in terms of logEC50 (on the log-concentration scale), not EC50 directly, so the null H0: logEC50 = 0 corresponds to testing EC50 = 1 on the concentration scale — a value with no intrinsic pharmacometric meaning. By default, the test statistic and p-value for logEC50_Intercept are suppressed (set to NA), while the confidence interval for logEC50 is retained. To work with the EC50 on the concentration scale, use back_transform = TRUE.

Simultaneous intervals

When simultaneous = TRUE, a single critical value is derived from the joint multivariate normal distribution of the standardised parameter estimates. The resulting intervals have simultaneous coverage at conf_level and will be wider than the individual (pointwise) intervals.

Multiplicity: p-value adjustment versus simultaneous intervals

A model with several parameters raises a multiple-comparisons problem: the more quantities you inspect, the more likely at least one spurious result appears by chance. summary() offers two, deliberately separate, tools for this, and it is worth being clear about how they differ because they are easy to conflate.

• p_adjust acts on the hypothesis tests. It takes the marginal (per-parameter) p-values and feeds them through stats::p.adjust(), which applies a sequential rule such as Holm or a Bonferroni scaling. These rules look only at the set of p-values; they do not use the estimated correlations between the parameters. Only the p_value column changes. The estimates, standard errors, test statistics, and confidence intervals are untouched.

• simultaneous acts on the interval estimates. It replaces the per-parameter critical value with a single, larger critical value taken from the joint multivariate normal distribution of the estimates (via mvtnorm::qmvnorm()), which does use the correlation structure from vcov(). Only the ci_lower and ci_upper columns change. The p-values and test statistics are untouched.

The two arguments are fully independent: you may set either, both, or neither, and each does exactly the one thing described above. Neither argument modifies the other's output.

Why the adjusted p-values and the intervals may disagree

Because the two corrections use different machinery, they will not, in general, agree on which parameters are "significant". A parameter can have a Holm-adjusted p-value below 1 - conf_level while its simultaneous confidence interval still contains zero, or the reverse. This is not a bug. The familiar duality — "the 95% interval excludes zero if and only if the two-sided test rejects at the 5% level" — holds only for a single, unadjusted Wald comparison. It breaks as soon as a multiplicity correction enters, for two reasons:

• the corrections answer different questions (a step-down rule on the p-values versus a joint critical region for the intervals), and

• they use different information (p.adjust() ignores the parameter correlations that the simultaneous interval is built from).

A further, smaller source of discrepancy: unless the profile-likelihood computation falls back to Wald intervals, the default (pointwise) intervals are profile-likelihood based, whereas the reported test statistics and p-values are Wald quantities, so even without any adjustment the two need not correspond exactly in nonlinear models.

Which one to use

Pick the tool that matches the claim you want to make, and interpret its output on its own terms rather than cross-checking one against the other:

• To report interval estimates that are jointly valid across all parameters, use simultaneous = TRUE.

• To control the family-wise (or false-discovery) error rate of a set of hypothesis tests, choose a p_adjust method.

Setting both is legitimate, but the adjusted p-values and the simultaneous intervals are then two separate summaries of multiplicity, not two views of the same one, and should be read as such.

Value

A tibble with one row per model parameter and columns for the estimate, standard error, test statistic, p-value, and confidence interval bounds. The column for the test statistic is named t_statistic for emaxnls models and z_statistic for emaxlogistic models. The return format is experimental and may change in future releases.

Examples

mod_c <- emax_nls(
  structural_model = rsp_1 ~ exp_1,
  covariate_model = list(E0 ~ cnt_a, Emax ~ 1, logEC50 ~ 1),
  data = emax_df,
  opts = emax_nls_options(max_time = 10)
)

# standard summary (logEC50_Intercept p-value suppressed by default)
summary(mod_c)

# show all tests, including the logEC50 intercept
summary(mod_c, suppress_nonsensical = FALSE)

# Bonferroni-adjusted p-values
summary(mod_c, p_adjust = "bonferroni")

# simultaneous confidence intervals
summary(mod_c, simultaneous = TRUE)

# adjusted confidence level
summary(mod_c, conf_level = 0.99)

# back-transform logEC50 and logHill to concentration scale
summary(mod_c, back_transform = TRUE)

# logistic emax equivalent
mod_b <- emax_logistic(
  structural_model = rsp_2 ~ exp_1,
  covariate_model = list(E0 ~ cnt_a, Emax ~ 1, logEC50 ~ 1),
  data = emax_df,
  opts = emax_logistic_options(max_time = 10)
)
summary(mod_b)

---

Variance-covariance matrix for an Emax regression

Description

Returns the estimated variance-covariance matrix of the model parameters. The square roots of the diagonal entries are the parameter standard errors.

Usage

## S3 method for class 'emaxnls'
vcov(object, ...)

Arguments

object	An emaxnls or emaxlogistic object
...	Ignored

Details

For emaxnls objects, the matrix is derived from the Hessian of the NLS objective at the parameter estimates (via stats::vcov.nls()). For emaxlogistic objects, it is derived from the Jacobian of the IRLS algorithm at convergence, which provides the correct asymptotic covariance matrix under binomial sampling.

Value

A square numeric matrix with rows and columns named by the model parameters

Examples

mod_c <- emax_nls(
  structural_model = rsp_1 ~ exp_1, 
  covariate_model = list(E0 ~ cnt_a, Emax ~ 1, logEC50 ~ 1), 
  data = emax_df,
  opts = emax_nls_options(max_time = 10)
)
vcov(mod_c)

mod_b <- emax_logistic(
  structural_model = rsp_2 ~ exp_1,
  covariate_model = list(E0 ~ cnt_a, Emax ~ 1, logEC50 ~ 1),
  data = emax_df,
  opts = emax_logistic_options(max_time = 10)
)
vcov(mod_b)

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