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Documentation: https://qihuangzhang.github.io/aftsplex/

Accelerated-failure-time (AFT) models with a natural-cubic-spline dose-response, corrected for additive measurement error in a multivariate surrogate via a generalised-least-squares (GLS) combiner and SIMEX, with a two-stage nonparametric bootstrap that propagates uncertainty from both the validation (Phase-1) and main-study (Phase-2) samples.

Installation

# install.packages("remotes")
remotes::install_github("QihuangZhang/aftsplex")

Quick start

library(aftsplex)

sim <- generate_aft_data(n = 2000, n_val = 500, seed = 1)

boot <- two_stage_bootstrap(
  survival   = sim$survival,
  validation = sim$validation,
  x_var      = "X_true",
  covariates = c("V1", "V2", "V3", "V4"),
  v_ref      = c(V1 = 30, V2 = 30, V3 = 0, V4 = 0),
  df         = 4,
  lambda     = seq(0.5, 2, 0.5),
  B          = 20,
  R          = 50
)

plot(boot$x_grid, boot$f_hat, type = "l",
     ylim = range(boot$lower, boot$upper),
     xlab = "X", ylab = "Centred linear predictor")
lines(boot$x_grid, boot$lower, lty = 2)
lines(boot$x_grid, boot$upper, lty = 2)

See vignette("quickstart", package = "aftsplex") for a fuller walk-through, vignette("simulation-study") for the Monte Carlo bias and ISE comparison across estimators, and vignette("sensitivity-df") for guidance on choosing the spline degrees of freedom.

Method

aftsplex implements a two-phase estimator:

  1. Phase 1. Multivariate linear measurement-error calibration on an external validation sample with paired (truth, surrogate) observations: log W*_ij = alpha_0j + alpha_1j * log W_i + e_ij. A GLS combiner weights the back-transformed surrogates into a single calibrated exposure with conditional variance.
  2. Phase 2. Natural-cubic-spline AFT model on the calibrated exposure, corrected for residual attenuation via SIMEX (Cook and Stefanski, 1994).

Inference uses a nested two-stage nonparametric bootstrap that resamples the validation and main-study samples jointly, addressing the plug-in-variance critique that applies whenever the validation sample is small relative to the main study.

References

  • Carroll, R. J., Kuchenhoff, H., Lombard, F., & Stefanski, L. A. (1996). Asymptotics for the SIMEX estimator in nonlinear measurement-error models. Journal of the American Statistical Association, 91, 242-250.
  • Cook, J. R., & Stefanski, L. A. (1994). Simulation-extrapolation estimation in parametric measurement-error models. Journal of the American Statistical Association, 89, 1314-1328.

License

MIT (c) 2026 Qihuang Zhang.