Centers of Excellence


Center for Causal Inference

New paper on 2-stage instrumental variables estimation

New paper on 2-stage instrumental variables estimation

Mar 26, 2018

A general approach to evaluating the bias of 2‐stage instrumental variable estimators

Fei Wan, Dylan Small, and Nandita Mitra

Unmeasured confounding is a common concern when researchers attempt to estimate a treatment effect using observational data or randomized studies with nonperfect compliance. To address this concern, instrumental variable methods, such as 2‐stage predictor substitution (2SPS) and 2‐stage residual inclusion (2SRI), have been widely adopted. In many clinical studies of binary and survival outcomes, 2SRI has been accepted as the method of choice over 2SPS, but a compelling theoretical rationale has not been postulated. We evaluate the bias and consistency in estimating the conditional treatment effect for both 2SPS and 2SRI when the outcome is binary, count, or time to event. We demonstrate analytically that the bias in 2SPS and 2SRI estimators can be reframed to mirror the problem of omitted variables in nonlinear models and that there is a direct relationship with the collapsibility of effect measures. In contrast to conclusions made by previous studies (Terza et al, 2008), we demonstrate that the consistency of 2SRI estimators only holds under the following conditions: (1) when the null hypothesis is true; (2) when the outcome model is collapsible; or (3) when estimating the nonnull causal effect from Cox or logistic regression models, the strong and unrealistic assumption that the effect of the unmeasured covariates on the treatment is proportional to their effect on the outcome needs to hold. We propose a novel dissimilarity metric to provide an intuitive explanation of the bias of 2SRI estimators in noncollapsible models and demonstrate that with increasing dissimilarity between the effects of the unmeasured covariates on the treatment versus outcome, the bias of 2SRI increases in magnitude.

Share this Content

About CCI

The Center for Causal Inference (CCI) is a research center that is operating under a partnership between Penn’s Center for Clinical Epidemiology and Biostatistics (CCEB), the Department of Biostatistics and Epidemiology, Rutgers School of Public Health, and Penn’s Wharton School. The mission of the CCI is to be a leading center for research and training in the development and application of causal inference theory and methods.

Contact Us

6th Floor Blockley Hall 
423 Guardian Drive 
Philadelphia, PA 19104 

Email us with general inquiries