Assessment of a Modified Sandwich Estimator for Generalized Estimating Equations with Application to Opioid Poisoning in MIMIC-IV ICU Patients

Longitudinal data is encountered frequently in many healthcare research areas to include the critical care environment. Repeated measures from the same subject are expected to correlate with each other. Models with binary outcomes are commonly used in this setting. Regression models for correlated binary outcomes are frequently fit using generalized estimating equations (GEE). The Liang and Zeger sandwich estimator is often used in GEE to produce unbiased standard error estimation for regression coefficients in large sample settings, even when the covariance structure is misspecified. The sandwich estimator performs optimally in balanced designs when the number of participants is large with few repeated measurements. The sandwich estimator’s asymptotic properties do not hold in small sample and rare-event settings. Under these conditions, the sandwich estimator underestimates the variances and is biased downwards. Here, the performance of a modified sandwich estimator is compared to the traditional Liang-Zeger estimator and alternative forms proposed by authors Morel, Pan, and Mancl-DeRouen. Each estimator’s performance was assessed with 95% coverage probabilities for the regression coefficients using simulated data under various combinations of sample sizes and outcome prevalence values with independence and autoregressive correlation structures. This research was motivated by investigations involving rare-event outcomes in intensive care unit settings.

General regression model for the subdistribution of a competing risk under left-truncation and right-censoring

Summary Left-truncation poses extra challenges for the analysis of complex time-to-event data. We propose a general semiparametric regression model for left-truncated and right-censored competing risks data that is based on a novel weighted conditional likelihood function. Targeting the subdistribution hazard, our parameter estimates are directly interpretable with regard to the cumulative incidence function. We compare different weights from recent literature and develop a heuristic interpretation from a cure model perspective that is based on pseudo risk sets. Our approach accommodates external time-dependent covariate effects on the subdistribution hazard. We establish consistency and asymptotic normality of the estimators and propose a sandwich estimator of the variance. In comprehensive simulation studies we demonstrate solid performance of the proposed method. Comparing the sandwich estimator with the inverse Fisher information matrix, we observe a bias for the inverse Fisher information matrix and diminished coverage probabilities in settings with a higher percentage of left-truncation. To illustrate the practical utility of the proposed method, we study its application to a large HIV vaccine efficacy trial dataset.

Modelling Extreme Rainfall Using Adjusted Sandwich Estimator

The Generalized Extreme Value (GEV) distribution is often used to describe the frequency of occurrence of extreme rainfall. Modelling the extreme event using the independent Generalized Extreme Value to spatial data fails to account the behaviour of dependency data. However, the wrong statistical assumption by this marginal approach can be adjusted using sandwich estimator. In this paper, we used the conventional method of the marginal fitting of generalized extreme value distribution to the extreme rainfall then corrected the standard error to account for inter-site dependence. We also applied the penalized maximum likelihood to improve the generalized parameter estimations. A case study of annual maximum rainfall from several stations at western Sabah is studied, and the results suggest that the variances were found to be greater than the standard error in the marginal estimation as the inter-site dependence being considered. Key words: Generalized Extreme Value theory, sandwich estimator, penalized maximum likelihood, annual maximum rainfall

The Robust Variance Estimator for Two-stage Models

This article discusses estimates of variance for two-stage models. We present the sandwich estimate of variance as an alternative to the Murphy–Topel estimate. The sandwich estimator has a simple formula that is similar to the formula for the Murphy–Topel estimator, and the two estimators are asymptotically equal when the assumed model distributions are true. The advantages of the sandwich estimate of variance are that it may be calculated for the complete parameter vector, and that it requires estimating equations instead of fully specified log likelihoods.