drda: Fit non-linear growth curves

In drda: Dose-Response Data Analysis

Fit non-linear growth curves

Description

Use the Newton's with a trust-region method to fit non-linear growth curves to observed data.

Usage

drda(
  formula,
  data,
  subset,
  weights,
  na.action,
  mean_function = "logistic4",
  lower_bound = NULL,
  upper_bound = NULL,
  start = NULL,
  max_iter = 1000
)

Arguments

formula	an object of class formula (or one that can be coerced to that class): a symbolic description of the model to be fitted. Currently supports only formulas of the type y ~ x.
data	an optional data frame, list or environment (or object coercible by as.data.frame to a data frame) containing the variables in the model. If not found in data, the variables are taken from environment(formula), typically the environment from which drda is called.
subset	an optional vector specifying a subset of observations to be used in the fitting process.
weights	an optional vector of weights to be used in the fitting process. If provided, weighted least squares is used with weights weights (that is, minimizing sum(weights * residuals^2)), otherwise ordinary least squares is used.
na.action	a function which indicates what should happen when the data contain NAs. The default is set by the na.action setting of options, and is na.fail if that is unset. The 'factory-fresh' default is na.omit. Another possible value is NULL, no action. Value na.exclude can be useful.
mean_function	the model to be fitted. See details for available models.
lower_bound	numeric vector with the minimum admissible values of the parameters. Use -Inf to specify an unbounded parameter.
upper_bound	numeric vector with the maximum admissible values of the parameters. Use Inf to specify an unbounded parameter.
start	starting values for the parameters.
max_iter	maximum number of iterations in the optimization algorithm.

Details

Available models

Generalized (5-parameter) logistic function

The 5-parameter logistic function can be selected by choosing mean_function = "logistic5" or mean_function = "l5". The function is defined here as

alpha + delta / (1 + nu * exp(-eta * (x - phi)))^(1 / nu)

where eta > 0 and nu > 0. When delta is positive (negative) the curve is monotonically increasing (decreasing).

Parameter alpha is the value of the function when x -> -Inf. Parameter delta is the (signed) height of the curve. Parameter eta represents the steepness (growth rate) of the curve. Parameter phi is related to the mid-value of the function. Parameter nu affects near which asymptote maximum growth occurs.

The value of the function when x -> Inf is alpha + delta. In dose-response studies delta can be interpreted as the maximum theoretical achievable effect.

4-parameter logistic function

The 4-parameter logistic function is the default model of drda. It can be explicitly selected by choosing mean_function = "logistic4" or mean_function = "l4". The function is obtained by setting nu = 1 in the generalized logistic function, that is

alpha + delta / (1 + exp(-eta * (x - phi)))

where eta > 0. When delta is positive (negative) the curve is monotonically increasing (decreasing).

Parameter alpha is the value of the function when x -> -Inf. Parameter delta is the (signed) height of the curve. Parameter eta represents the steepness (growth rate) of the curve. Parameter phi represents the x value at which the curve is equal to its mid-point, i.e. ⁠f(phi; alpha, delta, eta, phi) = alpha + delta / 2⁠.

The value of the function when x -> Inf is alpha + delta. In dose-response studies delta can be interpreted as the maximum theoretical achievable effect.

2-parameter logistic function

The 2-parameter logistic function can be selected by choosing mean_function = "logistic2" or mean_function = "l2". For a monotonically increasing curve set nu = 1, alpha = 0, and delta = 1:

1 / (1 + exp(-eta * (x - phi)))

For a monotonically decreasing curve set nu = 1, alpha = 1, and delta = -1:

1 - 1 / (1 + exp(-eta * (x - phi)))

where eta > 0. The lower bound of the curve is zero while the upper bound of the curve is one.

Parameter eta represents the steepness (growth rate) of the curve. Parameter phi represents the x value at which the curve is equal to its mid-point, i.e. ⁠f(phi; eta, phi) = 1 / 2⁠.

Gompertz function

The Gompertz function is the limit for nu -> 0 of the 5-parameter logistic function. It can be selected by choosing mean_function = "gompertz" or mean_function = "gz". The function is defined in this package as

alpha + delta * exp(-exp(-eta * (x - phi)))

where eta > 0.

Parameter alpha is the value of the function when x -> -Inf. Parameter delta is the (signed) height of the curve. Parameter eta represents the steepness (growth rate) of the curve. Parameter phi sets the displacement along the x-axis.

The value of the function when x -> Inf is alpha + delta. In dose-response studies delta can be interpreted as the maximum theoretical achievable effect.

The mid-point of the function, that is alpha + delta / 2, is achieved at x = phi - log(log(2)) / eta.

Generalized (5-parameter) log-logistic function

The 5-parameter log-logistic function is selected by setting mean_function = "loglogistic5" or mean_function = "ll5". The function is defined here as

alpha + delta * (x^eta / (x^eta + nu * phi^eta))^(1 / nu)

where x >= 0, eta > 0, phi > 0, and nu > 0. When delta is positive (negative) the curve is monotonically increasing (decreasing). The function is defined only for positive values of the predictor variable x.

Parameter alpha is the value of the function at x = 0. Parameter delta is the (signed) height of the curve. Parameter eta represents the steepness (growth rate) of the curve. Parameter phi is related to the mid-value of the function. Parameter nu affects near which asymptote maximum growth occurs.

The value of the function when x -> Inf is alpha + delta. In dose-response studies delta can be interpreted as the maximum theoretical achievable effect.

4-parameter log-logistic function

The 4-parameter log-logistic function is selected by setting mean_function = "loglogistic4" or mean_function = "ll4". The function is obtained by setting nu = 1 in the generalized log-logistic function, that is

alpha + delta * x^eta / (x^eta + phi^eta)

where x >= 0 and eta > 0. When delta is positive (negative) the curve is monotonically increasing (decreasing). The function is defined only for positive values of the predictor variable x.

Parameter alpha is the value of the function at x = 0. Parameter delta is the (signed) height of the curve. Parameter eta represents the steepness (growth rate) of the curve. Parameter phi represents the x value at which the curve is equal to its mid-point, i.e. ⁠f(phi; alpha, delta, eta, phi) = alpha + delta / 2⁠.

The value of the function when x -> Inf is alpha + delta. In dose-response studies delta can be interpreted as the maximum theoretical achievable effect.

2-parameter log-logistic function

The 2-parameter log-logistic function is selected by setting mean_function = "loglogistic2" or mean_function = "ll2". For a monotonically increasing curve set nu = 1, alpha = 0, and delta = 1:

x^eta / (x^eta + phi^eta)

For a monotonically decreasing curve set nu = 1, alpha = 1, and delta = -1:

1 - x^eta / (x^eta + phi^eta)

where x >= 0, eta > 0, and phi > 0. The lower bound of the curve is zero while the upper bound of the curve is one.

Parameter eta represents the steepness (growth rate) of the curve. Parameter phi represents the x value at which the curve is equal to its mid-point, i.e. ⁠f(phi; eta, phi) = 1 / 2⁠.

log-Gompertz function

The log-Gompertz function is the limit for nu -> 0 of the 5-parameter log-logistic function. It can be selected by choosing mean_function = "loggompertz" or mean_function = "lgz". The function is defined in this package as

alpha + delta * exp(-(phi / x)^eta)

where x > 0, eta > 0, and phi > 0. Note that the limit for x -> 0 is alpha. When delta is positive (negative) the curve is monotonically increasing (decreasing). The function is defined only for positive values of the predictor variable x.

Parameter alpha is the value of the function at x = 0. Parameter delta is the (signed) height of the curve. Parameter eta represents the steepness (growth rate) of the curve. Parameter phi sets the displacement along the x-axis.

The value of the function when x -> Inf is alpha + delta. In dose-response studies delta can be interpreted as the maximum theoretical achievable effect.

Constrained optimization

It is possible to search for the maximum likelihood estimates within pre-specified interval regions.

Note: Hypothesis testing is not available for constrained estimates because asymptotic approximations might not be valid.

Value

An object of class drda and model_fit, where model is the chosen mean function. It is a list containing the following components:

converged

boolean value assessing if the optimization algorithm converged or not.

iterations

total number of iterations performed by the optimization algorithm

constrained

boolean value set to TRUE if optimization was constrained.

estimated

boolean vector indicating which parameters were estimated from the data.

coefficients

maximum likelihood estimates of the model parameters.

rss

minimum value (found) of the residual sum of squares.

df.residuals

residual degrees of freedom.

fitted.values

fitted mean values.

residuals

residuals, that is response minus fitted values.

weights

(only for weighted fits) the specified weights.

mean_function

model that was used for fitting.

n

effective sample size.

sigma

corrected maximum likelihood estimate of the standard deviation.

loglik

maximum value (found) of the log-likelihood function.

fisher.info

observed Fisher information matrix evaluated at the maximum likelihood estimator.

vcov

approximate variance-covariance matrix of the model parameters.

call

the matched call.

terms

the terms object used.

model

the model frame used.

na.action

(where relevant) information returned by model.frame on the special handling of NAs.

Examples

# by default `drda` uses a 4-parameter logistic function for model fitting
fit_l4 <- drda(response ~ log_dose, data = voropm2)

# get a general overview of the results
summary(fit_l4)

# compare the model against a flat horizontal line and the full model
anova(fit_l4)

# 5-parameter logistic curve appears to be a better model
fit_l5 <- drda(response ~ log_dose, data = voropm2, mean_function = "l5")
plot(fit_l4, fit_l5)

# fit a 2-parameter logistic function
fit_l2 <- drda(response ~ log_dose, data = voropm2, mean_function = "l2")

# compare our models
anova(fit_l2, fit_l4)

# use log-logistic functions when utilizing doses (instead of log-doses)
# here we show the use of other arguments as well
fit_ll5 <- drda(
  response ~ dose, weights = weight, data = voropm2,
  mean_function = "loglogistic5", lower_bound = c(0.5, -1.5, 0, -Inf, 0.25),
  upper_bound = c(1.5, 0.5, 5, Inf, 3), start = c(1, -1, 3, 100, 1),
  max_iter = 10000
)

# note that the maximum likelihood estimate is outside the region of
# optimization: not only the variance-covariance matrix is now singular but
# asymptotic assumptions do not hold anymore.

drda documentation built on April 3, 2025, 6 p.m.