# Standard analyses with one dose realization

    library(ameras)

# Introduction

The main purpose of `ameras` is to fit association models when multiple realizations of an exposure are available. The same interface can also be used for a standard analysis with a single observed dose variable.

By default, `ameras()` fits regression calibration (`RC`). With a single dose realization, the regression-calibrated dose is just the supplied dose column, so the examples below omit the `methods` argument and use the default `RC` fit.

For non-Gaussian families, `ameras()` defaults to a linear excess relative risk model (`model = "ERR"`). To compare with ordinary `glm()` fits, use the exponential relative risk model (`model = "EXP"`), which puts the dose coefficient on the usual logit or log-link scale.

    data(data, package = "ameras")

    ## Use one exposure realization as the single observed dose.
    data$D <- data$V1
    head(data[c("D", "Y.gaussian", "Y.binomial", "Y.poisson", "X1", "X2")])
    #>            D  Y.gaussian Y.binomial Y.poisson X1 X2
    #> 1 0.42868043 -0.32647093          0         0  0  0
    #> 2 0.73321154 -0.18734036          1         0  1  0
    #> 3 0.70369712  0.08404044          0         2  0  0
    #> 4 0.01845324  0.22432504          0         0  0  0
    #> 5 0.39389441 -0.46317255          0         0  1  0
    #> 6 0.01493158 -1.41036573          0         0  1  1

This small helper prints matching coefficients from an `ameras` fit and a standard R model. The dose coefficient is named `dose` by `ameras` and `D` by the standard model.

    compare_coefficients <- function(ameras_fit, standard_fit) {
      ameras_terms <- c("(Intercept)", "X1", "X2", "dose")
      standard_terms <- c("(Intercept)", "X1", "X2", "D")

      out <- data.frame(
        term = ameras_terms,
        ameras = unname(ameras_fit$RC$coefficients[ameras_terms]),
        standard = unname(stats::coef(standard_fit)[standard_terms])
      )

      out$ameras <- round(out$ameras, 4)
      out$standard <- round(out$standard, 4)
      out
    }

# Gaussian outcome

For a Gaussian outcome, a single-dose `ameras()` fit gives the same regression coefficients as `lm()`, with only a small numerical difference. The `ameras` fit also estimates `sigma`, so the comparison below only shows the regression coefficients.

    fit_ameras_gaussian <- ameras(Y.gaussian ~ dose(D) + X1 + X2,
                                  data = data,
                                  family = "gaussian")

    fit_lm <- lm(Y.gaussian ~ D + X1 + X2, data = data)

    compare_coefficients(fit_ameras_gaussian, fit_lm)
    #>          term  ameras standard
    #> 1 (Intercept) -1.2903  -1.2902
    #> 2          X1  0.4938   0.4937
    #> 3          X2 -0.5152  -0.5152
    #> 4        dose  1.0920   1.0920

The usual `amerasfit` methods are available, including `summary()`, `coef()`, `vcov()`, and `confint()`.

    fit_ameras_gaussian <- confint(fit_ameras_gaussian,
                                   type = "wald.orig",
                                   print = FALSE)
    summary(fit_ameras_gaussian)
    #> Call:
    #> ameras(formula = Y.gaussian ~ dose(D) + X1 + X2, data = data,
    #>     family = "gaussian")
    #>
    #> Rows: 3000
    #>
    #> Total CPU runtime: 0.1 seconds
    #>
    #> CPU runtime in seconds by method:
    #>
    #>  Method   Fit  CI Total
    #>      RC 0.063 0.0 0.063
    #>
    #> Summary of coefficients by method:
    #>
    #>  Method        Term Estimate      SE CI.lower CI.upper
    #>      RC (Intercept)  -1.2903 0.03818  -1.3651  -1.2154
    #>      RC          X1   0.4938 0.04236   0.4107   0.5768
    #>      RC          X2  -0.5152 0.05206  -0.6172  -0.4131
    #>      RC        dose   1.0920 0.02095   1.0509   1.1330
    #>      RC       sigma   1.1597 0.01497   1.1304   1.1891

# Binary outcome

For a binary outcome, specify `model = "EXP"` to match the usual logistic regression parameterization used by `glm(..., family = binomial())`.

    fit_ameras_binomial <- ameras(Y.binomial ~ dose(D, model = "EXP") + X1 + X2,
                                  data = data,
                                  family = "binomial")

    fit_glm_binomial <- glm(Y.binomial ~ D + X1 + X2,
                            data = data,
                            family = binomial())

    compare_coefficients(fit_ameras_binomial, fit_glm_binomial)
    #>          term  ameras standard
    #> 1 (Intercept) -0.9661  -0.9661
    #> 2          X1  0.4513   0.4513
    #> 3          X2 -0.3356  -0.3355
    #> 4        dose  0.4374   0.4374

# Count outcome

The same idea applies to Poisson regression. Again, `model = "EXP"` makes the `ameras` dose term directly comparable to the coefficient for `D` in `glm(..., family = poisson())`.

    fit_ameras_poisson <- ameras(Y.poisson ~ dose(D, model = "EXP") + X1 + X2,
                                 data = data,
                                 family = "poisson")

    fit_glm_poisson <- glm(Y.poisson ~ D + X1 + X2,
                           data = data,
                           family = poisson())

    compare_coefficients(fit_ameras_poisson, fit_glm_poisson)
    #>          term  ameras standard
    #> 1 (Intercept) -0.9178  -0.9178
    #> 2          X1  0.5140   0.5140
    #> 3          X2 -0.3569  -0.3570
    #> 4        dose  0.3821   0.3821

# A note on comparison with other software

For a single dose realization, or for `RC` with multiple realizations after replacing the dose by its realization-specific mean, point estimates should generally agree with other software when the same likelihood, dose-response model, covariates, and parameterization are used.

Standard errors and Wald confidence intervals may nevertheless differ. For `RC`, `ERC`, and `MCML`, `ameras` computes variance-covariance matrices from the observed information, using a numerical Hessian of the negative log-likelihood at the optimum. Other software may use expected Fisher information, a scoring-based approximation, a different treatment of parameter constraints, or a different internal parameter scale. These choices can lead to different standard errors even when coefficient estimates agree closely.

# Moving to multiple realizations

Once multiple exposure realizations are available, the formula changes only in the `dose()` term. For example, replacing `D` by `V1:V10` fits the default `RC` analysis using all 10 realizations:

    fit_ameras_rc <- ameras(Y.binomial ~ dose(V1:V10, model = "EXP") + X1 + X2,
                            data = data,
                            family = "binomial")
    summary(fit_ameras_rc)
    #> Call:
    #> ameras(formula = Y.binomial ~ dose(V1:V10, model = "EXP") + X1 +
    #>     X2, data = data, family = "binomial")
    #>
    #> Rows: 3000
    #>
    #> Total CPU runtime: 0.1 seconds
    #>
    #> CPU runtime in seconds by method:
    #>
    #>  Method   Fit  CI Total
    #>      RC 0.078 0.0 0.078
    #>
    #> Summary of coefficients by method:
    #>
    #>  Method        Term Estimate      SE
    #>      RC (Intercept)  -0.9760 0.07190
    #>      RC          X1   0.4460 0.07667
    #>      RC          X2  -0.3359 0.09596
    #>      RC        dose   0.4471 0.04101
    #>
    #> Note: confidence intervals not yet computed. Use confint() to add them.

Other methods can then be added through the `methods` argument:

    fit_ameras_all <- ameras(Y.binomial ~ dose(V1:V10, model = "EXP") + X1 + X2,
                             data = data,
                             family = "binomial",
                             methods = c("RC", "ERC", "MCML", "FMA", "BMA"))