skip to main content
US FlagAn official website of the United States government
dot gov icon
Official websites use .gov
A .gov website belongs to an official government organization in the United States.
https lock icon
Secure .gov websites use HTTPS
A lock ( lock ) or https:// means you've safely connected to the .gov website. Share sensitive information only on official, secure websites.

Attention:

The DOI auto-population feature in the Public Access Repository (PAR) will be unavailable from 4:00 PM ET on Tuesday, July 8 until 4:00 PM ET on Wednesday, July 9 due to scheduled maintenance. We apologize for the inconvenience caused.

Explore Research Products in the PAR
It may take a few hours for recently added research products to appear in PAR search results.


Title: Sensitivity analysis for unmeasured confounding in coarse Structural Nested Mean Models
Coarse Structural Nested Mean Models (SNMMs, Robins (2000)) and G-estimation can be used to estimate the causal effect of a time-varying treatment from longitudinal observational studies. However, they rely on an untestable assumption of no unmeasured confounding. In the presence of unmeasured confounders, the unobserved potential outcomes are not missing at random, and standard G-estimation leads to biased effect estimates. To remedy this, we investigate the sensitivity of G-estimators of coarse SNMMs to unmeasured confounding, assuming a nonidentifiable bias function which quantifies the impact of unmeasured confounding on the average potential outcome. We present adjusted G-estimators of coarse SNMM parameters and prove their consistency, under the bias modeling for unmeasured confounding. We apply this to a sensitivity analysis for the effect of the ART initiation time on the mean CD4 count at year 2 after infection in HIV-positive patients, based on the prospective Acute and Early Disease Research Program.  more » « less
Award ID(s):
1854934
PAR ID:
10357268
Author(s) / Creator(s):
;
Date Published:
Journal Name:
Statistica sinica
Volume:
28
ISSN:
1996-8507
Page Range / eLocation ID:
1703–1723
Format(s):
Medium: X
Sponsoring Org:
National Science Foundation
More Like this
  1. ; ; (, Biometrika)
    Summary Structural failure time models are causal models for estimating the effect of time-varying treatments on a survival outcome. G-estimation and artificial censoring have been proposed for estimating the model parameters in the presence of time-dependent confounding and administrative censoring. However, most existing methods require manually pre-processing data into regularly spaced data, which may invalidate the subsequent causal analysis. Moreover, the computation and inference are challenging due to the nonsmoothness of artificial censoring. We propose a class of continuous-time structural failure time models that respects the continuous-time nature of the underlying data processes. Under a martingale condition of no unmeasured confounding, we show that the model parameters are identifiable from a potentially infinite number of estimating equations. Using the semiparametric efficiency theory, we derive the first semiparametric doubly robust estimators, which are consistent if the model for the treatment process or the failure time model, but not necessarily both, is correctly specified. Moreover, we propose using inverse probability of censoring weighting to deal with dependent censoring. In contrast to artificial censoring, our weighting strategy does not introduce nonsmoothness in estimation and ensures that resampling methods can be used for inference. 
    more » « less
  2. ; ; (, Journal of Causal Inference)
    Abstract Investigating the causal relationship between exposure and time-to-event outcome is an important topic in biomedical research. Previous literature has discussed the potential issues of using hazard ratio (HR) as the marginal causal effect measure due to noncollapsibility. In this article, we advocate using restricted mean survival time (RMST) difference as a marginal causal effect measure, which is collapsible and has a simple interpretation as the difference of area under survival curves over a certain time horizon. To address both measured and unmeasured confounding, a matched design with sensitivity analysis is proposed. Matching is used to pair similar treated and untreated subjects together, which is generally more robust than outcome modeling due to potential misspecifications. Our propensity score matched RMST difference estimator is shown to be asymptotically unbiased, and the corresponding variance estimator is calculated by accounting for the correlation due to matching. Simulation studies also demonstrate that our method has adequate empirical performance and outperforms several competing methods used in practice. To assess the impact of unmeasured confounding, we develop a sensitivity analysis strategy by adapting the E -value approach to matched data. We apply the proposed method to the Atherosclerosis Risk in Communities Study (ARIC) to examine the causal effect of smoking on stroke-free survival. 
    more » « less
  3. ; ; ; ; (, Journal of the Royal Statistical Society Series A: Statistics in Society)
    Abstract Assessing sensitivity to unmeasured confounding is an important step in observational studies, which typically estimate effects under the assumption that all confounders are measured. In this paper, we develop a sensitivity analysis framework for balancing weights estimators, an increasingly popular approach that solves an optimization problem to obtain weights that directly minimizes covariate imbalance. In particular, we adapt a sensitivity analysis framework using the percentile bootstrap for a broad class of balancing weights estimators. We prove that the percentile bootstrap procedure can, with only minor modifications, yield valid confidence intervals for causal effects under restrictions on the level of unmeasured confounding. We also propose an amplification—a mapping from a one-dimensional sensitivity analysis to a higher dimensional sensitivity analysis—to allow for interpretable sensitivity parameters in the balancing weights framework. We illustrate our method through extensive real data examples. 
    more » « less
  4. ; ; ; (, Statistics in Medicine)
    ABSTRACT Disparities in health or well‐being experienced by minority groups can be difficult to study using the traditional exposure‐outcome paradigm in causal inference, since potential outcomes in variables such as race or sexual minority status are challenging to interpret. Causal decomposition analysis addresses this gap by positing causal effects on disparities under interventions to other intervenable exposures that may play a mediating role in the disparity. While invoking weaker assumptions than causal mediation approaches, decomposition analyses are often conducted in observational settings and require uncheckable assumptions that eliminate unmeasured confounders. Leveraging the marginal sensitivity model, we develop a sensitivity analysis for weighted causal decomposition estimators and use the percentile bootstrap to construct valid confidence intervals for causal effects on disparities. We also propose a two‐parameter reformulation that enhances interpretability and facilitates an intuitive understanding of the plausibility of unmeasured confounders and their effects. We illustrate our framework on a study examining the effect of parental support on disparities in suicidal ideation among sexual minority youth. We find that the effect is small and sensitive to unmeasured confounding, suggesting that further screening studies are needed to identify mitigating interventions in this vulnerable population. 
    more » « less
  5. ; ; ; (, Lifetime Data Analysis)
    Abstract In this study, we focus on estimating the heterogeneous treatment effect (HTE) for survival outcome. The outcome is subject to censoring and the number of covariates is high-dimensional. We utilize data from both the randomized controlled trial (RCT), considered as the gold standard, and real-world data (RWD), possibly affected by hidden confounding factors. To achieve a more efficient HTE estimate, such integrative analysis requires great insight into the data generation mechanism, particularly the accurate characterization of unmeasured confounding effects/bias. With this aim, we propose a penalized-regression-based integrative approach that allows for the simultaneous estimation of parameters, selection of variables, and identification of the existence of unmeasured confounding effects. The consistency, asymptotic normality, and efficiency gains are rigorously established for the proposed estimate. Finally, we apply the proposed method to estimate the HTE of lobar/sublobar resection on the survival of lung cancer patients. The RCT is a multicenter non-inferiority randomized phase 3 trial, and the RWD comes from a clinical oncology cancer registry in the United States. The analysis reveals that the unmeasured confounding exists and the integrative approach does enhance the efficiency for the HTE estimation. 
    more » « less
  • Citation Formats
  • MLA
  • APA
  • Chicago
  • BibTeX
  • Save / Share this Record
  • Send to Email