standardize_parfrailty: Regression standardization in shared frailty gamma-Weibull...

In stdReg2: Regression Standardization for Causal Inference

Regression standardization in shared frailty gamma-Weibull models

Description

standardize_parfrailty performs regression standardization in shared frailty gamma-Weibull models, at specified values of the exposure, over the sample covariate distribution. Let T, X, and Z be the survival outcome, the exposure, and a vector of covariates, respectively. standardize_parfrailty fits a parametric frailty model to estimate the standardized survival function \theta(t,x)=E\{S(t|X=x,Z)\}, where t is a specific value of T, x is a specific value of X, and the expectation is over the marginal distribution of Z.

Usage

standardize_parfrailty(
  formula,
  data,
  values,
  times,
  clusterid,
  ci_level = 0.95,
  ci_type = "plain",
  contrasts = NULL,
  family = "gaussian",
  reference = NULL,
  transforms = NULL
)

Arguments

formula	The formula which is used to fit the model for the outcome.
data	The data.
values	A named list or data.frame specifying the variables and values at which marginal means of the outcome will be estimated.
times	A vector containing the specific values of T at which to estimate the standardized survival function.
clusterid	An optional string containing the name of a cluster identification variable when data are clustered.
ci_level	Coverage probability of confidence intervals.
ci_type	A string, indicating the type of confidence intervals. Either "plain", which gives untransformed intervals, or "log", which gives log-transformed intervals.
contrasts	A vector of contrasts in the following format: If set to "difference" or "ratio", then \psi(x)-\psi(x_0) or \psi(x) / \psi(x_0) are constructed, where x_0 is a reference level specified by the reference argument. Has to be NULL if no references are specified.
family	The family argument which is used to fit the glm model for the outcome.
reference	A vector of reference levels in the following format: If contrasts is not NULL, the desired reference level(s). This must be a vector or list the same length as contrasts, and if not named, it is assumed that the order is as specified in contrasts.
transforms	A vector of transforms in the following format: If set to "log", "logit", or "odds", the standardized mean \theta(x) is transformed into \psi(x)=\log\{\theta(x)\}, \psi(x)=\log[\theta(x)/\{1-\theta(x)\}], or \psi(x)=\theta(x)/\{1-\theta(x)\}, respectively. If the vector is NULL, then \psi(x)=\theta(x).

Details

standardize_parfrailty fits a shared frailty gamma-Weibull model

\lambda(t_{ij}|X_{ij},Z_{ij})=\lambda(t_{ij};\alpha,\eta)U_iexp\{h(X_{ij},Z_{ij};\beta)\}

, with parameterization as described in the help section for parfrailty. Integrating out the gamma frailty gives the survival function

S(t|X,Z)=[1+\phi\Lambda_0(t;\alpha,\eta)\exp\{h(X,Z;\beta)\}]^{-1/\phi},

where \Lambda_0(t;\alpha,\eta) is the cumulative baseline hazard

(t/\alpha)^{\eta}.

The ML estimates of (\alpha,\eta,\phi,\beta) are used to obtain estimates of the survival function S(t|X=x,Z):

\hat{S}(t|X=x,Z)=[1+\hat{\phi}\Lambda_0(t;\hat{\alpha},\hat{\eta})\exp\{h(X,Z;\hat{\beta})\}]^{-1/\hat{\phi}}.

For each t in the t argument and for each x in the x argument, these estimates are averaged across all subjects (i.e. all observed values of Z) to produce estimates

\hat{\theta}(t,x)=\sum_{i=1}^n \hat{S}(t|X=x,Z_i)/n.

The variance for \hat{\theta}(t,x) is obtained by the sandwich formula.

Value

An object of class std_surv. Obtain numeric results by using tidy.std_surv. This is a list with the following components:

res_contrast

An unnamed list with one element for each of the requested contrasts. Each element is itself a list with the elements:

call

The function call

input

A list with components used in the estimation

measure

Either "survival" or "rmean"

est

Estimated counterfactual means and standard errors for each exposure level

vcov

Estimated covariance matrix of counterfactual means for each time

est_table

Data.frame of the estimates of the contrast with inference

times

The vector of times used in the calculation

transform

The transform argument used for this contrast

contrast

The requested contrast type

reference

The reference level of the exposure

ci_type

Confidence interval type

ci_level

Confidence interval level

res

A named list with the elements:

call

The function call

input

A list with components used in the estimation

measure

Either "survival" or "rmean"

est

Estimated counterfactual means and standard errors for each exposure level

vcov

Estimated covariance matrix of counterfactual means for each time

Note

Standardized survival functions are sometimes referred to as (direct) adjusted survival functions in the literature.

standardize_coxph/standardize_parfrailty does not currently handle time-varying exposures or covariates.

standardize_coxph/standardize_parfrailty internally loops over all values in the t argument. Therefore, the function will usually be considerably faster if length(t) is small.

The variance calculation performed by standardize_coxph does not condition on the observed covariates \bar{Z}=(Z_1,...,Z_n). To see how this matters, note that

var\{\hat{\theta}(t,x)\}=E[var\{\hat{\theta}(t,x)|\bar{Z}\}]+var[E\{\hat{\theta}(t,x)|\bar{Z}\}].

The usual parameter \beta in a Cox proportional hazards model does not depend on \bar{Z}. Thus, E(\hat{\beta}|\bar{Z}) is independent of \bar{Z} as well (since E(\hat{\beta}|\bar{Z})=\beta), so that the term var[E\{\hat{\beta}|\bar{Z}\}] in the corresponding variance decomposition for var(\hat{\beta}) becomes equal to 0. However, \theta(t,x) depends on \bar{Z} through the average over the sample distribution for Z, and thus the term var[E\{\hat{\theta}(t,x)|\bar{Z}\}] is not 0, unless one conditions on \bar{Z}. The variance calculation by Gail and Byar (1986) ignores this term, and thus effectively conditions on \bar{Z}.

Author(s)

Arvid Sjölander

References

Chang I.M., Gelman G., Pagano M. (1982). Corrected group prognostic curves and summary statistics. Journal of Chronic Diseases 35, 669-674.

Dahlqwist E., Pawitan Y., Sjölander A. (2019). Regression standardization and attributable fraction estimation with between-within frailty models for clustered survival data. Statistical Methods in Medical Research 28(2), 462-485.

Gail M.H. and Byar D.P. (1986). Variance calculations for direct adjusted survival curves, with applications to testing for no treatment effect. Biometrical Journal 28(5), 587-599.

Makuch R.W. (1982). Adjusted survival curve estimation using covariates. Journal of Chronic Diseases 35, 437-443.

Examples

require(survival)

# simulate data
set.seed(6)
n <- 300
m <- 3
alpha <- 1.5
eta <- 1
phi <- 0.5
beta <- 1
id <- rep(1:n, each = m)
U <- rep(rgamma(n, shape = 1 / phi, scale = phi), each = m)
X <- rnorm(n * m)
# reparameterize scale as in rweibull function
weibull.scale <- alpha / (U * exp(beta * X))^(1 / eta)
T <- rweibull(n * m, shape = eta, scale = weibull.scale)

# right censoring
C <- runif(n * m, 0, 10)
D <- as.numeric(T < C)
T <- pmin(T, C)

# strong left-truncation
L <- runif(n * m, 0, 2)
incl <- T > L
incl <- ave(x = incl, id, FUN = sum) == m
dd <- data.frame(L, T, D, X, id)
dd <- dd[incl, ]

fit.std <- standardize_parfrailty(
  formula = Surv(L, T, D) ~ X,
  data = dd,
  values = list(X = seq(-1, 1, 0.5)),
  times = 1:5,
  clusterid = "id"
)
print(fit.std)
plot(fit.std)

stdReg2 documentation built on April 13, 2025, 5:12 p.m.