Semiparametric Sensitivity Analysis: Unmeasured Confounding In Observational Studies

Establishing cause-effect relationships from observational data often relies on untestable assumptions. It is crucial to know whether, and to what extent, the conclusions drawn from nonexperimental studies are robust to potential unmeasured confounding. In this paper, we focus on the average causal effect (ACE) as our target of inference. We build on the work of Franks et al. [2019] and Robins et al. [2000] by specifying non-identified sensitivity parameters that govern a contrast between the conditional (on measured covariates) distributions of the outcome under treatment (control) between treated and untreated individuals. We use semiparametric theory to derive the non-parametric efficient influence function of the ACE, for fixed sensitivity parameters. We use this influence function to construct a one-step bias-corrected estimator of the ACE. Our estimator depends on semiparametric models for the distribution of the observed data; importantly, these models do not impose any restrictions on the values of sensitivity analysis parameters. We establish sufficient conditions ensuring that our estimator has √ n asymptotics. We use our methodology to evaluate the causal effect of smoking during pregnancy on birth weight. We also evaluate the performance of estimation procedure in a simulation study.

[1]  John Duchi,et al.  BOUNDS ON THE CONDITIONAL AND AVERAGE TREATMENT EFFECT WITH UNOBSERVED CONFOUNDING FACTORS. , 2018, Annals of statistics.

[2]  James M. Robins,et al.  Unified Methods for Censored Longitudinal Data and Causality , 2003 .

[3]  James M. Robins,et al.  Association, Causation, And Marginal Structural Models , 1999, Synthese.

[4]  M. J. van der Laan,et al.  The International Journal of Biostatistics Targeted Maximum Likelihood Learning , 2011 .

[5]  J. Robins A new approach to causal inference in mortality studies with a sustained exposure period—application to control of the healthy worker survivor effect , 1986 .

[6]  Judea Pearl,et al.  Identification of Joint Interventional Distributions in Recursive Semi-Markovian Causal Models , 2006, AAAI.

[7]  Carlos Cinelli,et al.  Making sense of sensitivity: extending omitted variable bias , 2019, Journal of the Royal Statistical Society: Series B (Statistical Methodology).

[8]  J. Robins,et al.  Estimation of Regression Coefficients When Some Regressors are not Always Observed , 1994 .

[9]  Sivaraman Balakrishnan,et al.  Sharp instruments for classifying compliers and generalizing causal effects , 2018, The Annals of Statistics.

[10]  L. Larsen,et al.  Stereologic examination of placentas from mothers who smoke during pregnancy. , 2002, American journal of obstetrics and gynecology.

[11]  Edward H. Kennedy,et al.  Sensitivity Analysis via the Proportion of Unmeasured Confounding , 2019, 1912.02793.

[12]  Masataka Harada,et al.  A flexible, interpretable framework for assessing sensitivity to unmeasured confounding , 2016, Statistics in medicine.

[13]  Joel L. Horowitz,et al.  Nonparametric estimation of an additive model with a link function , 2002, math/0508595.

[14]  M. Chavance [Jackknife and bootstrap]. , 1992, Revue d'epidemiologie et de sante publique.

[15]  R. Beran Prepivoting to reduce level error of confidence sets , 1987 .

[16]  J. Robins,et al.  Sensitivity Analyses for Unmeasured Confounding Assuming a Marginal Structural Model for Repeated Measures , 2022 .

[17]  D. Rubin,et al.  Principal Stratification in Causal Inference , 2002, Biometrics.

[18]  P. Lehtovirta,et al.  THE ACUTE EFFECT OF SMOKING ON INTERVILLOUS BLOOD FLOW OF THE PLACENTA , 1978, British journal of obstetrics and gynaecology.

[19]  Victor Veitch,et al.  Sense and Sensitivity Analysis: Simple Post-Hoc Analysis of Bias Due to Unobserved Confounding , 2020, NeurIPS.

[20]  James M. Robins,et al.  MINIMAX ESTIMATION OF A FUNCTIONAL ON A STRUCTURED , 2016 .

[21]  Jennifer L. Hill,et al.  Assessing Sensitivity to Unmeasured Confounding Using a Simulated Potential Confounder , 2016 .

[22]  D. Scharfstein,et al.  Causal inference for non-mortality outcomes in the presence of death. , 2007, Biostatistics.

[23]  Aad van der Vaart,et al.  Higher order influence functions and minimax estimation of nonlinear functionals , 2008, 0805.3040.

[24]  Dylan S. Small,et al.  Sensitivity analysis for inverse probability weighting estimators via the percentile bootstrap , 2017, Journal of the Royal Statistical Society: Series B (Statistical Methodology).

[25]  P. Hall,et al.  On bootstrap resampling and iteration , 1988 .

[26]  Liping Zhu,et al.  A Semiparametric Approach to Dimension Reduction , 2012, Journal of the American Statistical Association.

[27]  D. Rubin,et al.  Assessing Sensitivity to an Unobserved Binary Covariate in an Observational Study with Binary Outcome , 1983 .

[28]  Chin-Tsang Chiang,et al.  New estimation and inference procedures for a single-index conditional distribution model , 2012, J. Multivar. Anal..

[29]  Onyebuchi A Arah,et al.  Bias Formulas for Sensitivity Analysis of Unmeasured Confounding for General Outcomes, Treatments, and Confounders , 2011, Epidemiology.

[30]  S. Joyce,et al.  Fetal toxicity associated with maternal carbon monoxide poisoning. , 1988, Annals of emergency medicine.

[31]  P. Rosenbaum,et al.  Dual and simultaneous sensitivity analysis for matched pairs , 1998 .

[32]  C. Manski Nonparametric Bounds on Treatment Effects , 1989 .

[33]  J. Samet,et al.  Systematic review and meta-analysis of miscarriage and maternal exposure to tobacco smoke during pregnancy. , 2014, American journal of epidemiology.

[34]  C. Shen,et al.  Sensitivity analysis for causal inference using inverse probability weighting , 2011, Biometrical journal. Biometrische Zeitschrift.

[35]  Elizabeth A. Stuart,et al.  An Introduction to Sensitivity Analysis for Unobserved Confounding in Nonexperimental Prevention Research , 2013, Prevention Science.

[36]  Wen-Xin Zhou,et al.  A New Principle for Tuning-Free Huber Regression , 2021, Statistica Sinica.

[37]  Alexander D'Amour,et al.  Flexible Sensitivity Analysis for Observational Studies Without Observable Implications , 2018, Journal of the American Statistical Association.

[38]  Semiparametric Inference For Causal Effects In Graphical Models With Hidden Variables , 2020, ArXiv.

[39]  Chin‐Tsang Chiang,et al.  An Effective Semiparametric Estimation Approach for the Sufficient Dimension Reduction Model , 2017 .

[40]  J. van der Laan,et al.  Sensitivity Analysis for Causal Inference Under Unmeasured Confounding and Measurement Error Problems , 2016 .

[41]  P. Hall On the Bootstrap and Confidence Intervals , 1986 .

[42]  Eric J. Tchetgen Tchetgen,et al.  A Semiparametric Approach to Model-based Sensitivity Analysis in Observational Studies , 2019 .

[43]  V. Arıca,et al.  Epidemiology, pathophysiology, clinical evaluation, and treatment of carbon monoxide poisoning in child, infant, and fetus , 2017, Northern clinics of Istanbul.

[44]  K J Dalton,et al.  Morphometric differences between the placental vasculature of non‐smokers, smokers and ex‐smokers , 1989, British journal of obstetrics and gynaecology.

[45]  R. Harding,et al.  Influence of maternal tobacco smoking during pregnancy on uterine, umbilical and fetal cerebral artery blood flows. , 2004, Early human development.

[46]  Joseph A. C. Delaney Sensitivity analysis , 2018, The African Continental Free Trade Area: Economic and Distributional Effects.

[47]  Matias D. Cattaneo,et al.  Efficient semiparametric estimation of multi-valued treatment effects under ignorability , 2010 .

[48]  Liping Zhu,et al.  EFFICIENT ESTIMATION IN SUFFICIENT DIMENSION REDUCTION. , 2013, Annals of statistics.

[49]  G. W. Imbens Sensitivity to Exogeneity Assumptions in Program Evaluation , 2003 .

[50]  T. Mayhew,et al.  A quantitative study on the effects of maternal smoking on placental morphology and cadmium concentration. , 2000, Placenta.

[51]  A. Tsiatis Semiparametric Theory and Missing Data , 2006 .

[52]  E. C. Hammond,et al.  Smoking and lung cancer: recent evidence and a discussion of some questions. , 1959, Journal of the National Cancer Institute.

[53]  T. Shakespeare,et al.  Observational Studies , 2003 .

[54]  D. Almond,et al.  The Costs of Low Birth Weight , 2004 .

[55]  D. Rubin,et al.  The central role of the propensity score in observational studies for causal effects , 1983 .

[56]  Jason P Fine,et al.  Nonparametric Bounds and Sensitivity Analysis of Treatment Effects. , 2014, Statistical science : a review journal of the Institute of Mathematical Statistics.

[57]  M. Kenward,et al.  An Introduction to the Bootstrap , 2007 .

[58]  P. Bickel Efficient and Adaptive Estimation for Semiparametric Models , 1993 .

[59]  J. Robins,et al.  Estimating causal effects from epidemiological data , 2006, Journal of Epidemiology and Community Health.

[60]  Sivaraman Balakrishnan,et al.  Semiparametric Counterfactual Density Estimation , 2021, Biometrika.

[61]  Tyler J. VanderWeele,et al.  Sensitivity Analysis Without Assumptions , 2015, Epidemiology.

[62]  J. Robins,et al.  Sensitivity Analysis for Selection bias and unmeasured Confounding in missing Data and Causal inference models , 2000 .

[63]  J. Pearl Causality: Models, Reasoning and Inference , 2000 .