Estimating inverse probability weights using super learner when weight‐model specification is unknown in a marginal structural Cox model context

Correct specification of the inverse probability weighting (IPW) model is necessary for consistent inference from a marginal structural Cox model (MSCM). In practical applications, researchers are typically unaware of the true specification of the weight model. Nonetheless, IPWs are commonly estimated using parametric models, such as the main-effects logistic regression model. In practice, assumptions underlying such models may not hold and data-adaptive statistical learning methods may provide an alternative. Many candidate statistical learning approaches are available in the literature. However, the optimal approach for a given dataset is impossible to predict. Super learner (SL) has been proposed as a tool for selecting an optimal learner from a set of candidates using cross-validation. In this study, we evaluate the usefulness of a SL in estimating IPW in four different MSCM simulation scenarios, in which we varied the specification of the true weight model specification (linear and/or additive). Our simulations show that, in the presence of weight model misspecification, with a rich and diverse set of candidate algorithms, SL can generally offer a better alternative to the commonly used statistical learning approaches in terms of MSE as well as the coverage probabilities of the estimated effect in an MSCM. The findings from the simulation studies guided the application of the MSCM in a multiple sclerosis cohort from British Columbia, Canada (1995-2008), to estimate the impact of beta-interferon treatment in delaying disability progression. Copyright © 2017 John Wiley & Sons, Ltd.

[1]  P. Gustafson,et al.  Investigation of heterogeneity in the association between interferon beta and disability progression in multiple sclerosis: an observational study , 2014, European journal of neurology.

[2]  E. Moodie,et al.  Flexible Marginal Structural Models for Estimating the Cumulative Effect of a Time-Dependent Treatment on the Hazard: Reassessing the Cardiovascular Risks of Didanosine Treatment in the Swiss HIV Cohort Study , 2014 .

[3]  P. Gustafson,et al.  Association between use of interferon beta and progression of disability in patients with relapsing-remitting multiple sclerosis. , 2012, JAMA.

[4]  Til Stürmer,et al.  The role of the c‐statistic in variable selection for propensity score models , 2011, Pharmacoepidemiology and drug safety.

[5]  Jessica A. Myers,et al.  Myers et al. Respond to “Understanding Bias Amplification” , 2011 .

[6]  J. Myers,et al.  Effects of adjusting for instrumental variables on bias and precision of effect estimates. , 2011, American journal of epidemiology.

[7]  Chih-Jen Lin,et al.  LIBSVM: A library for support vector machines , 2011, TIST.

[8]  L. J. Wei,et al.  The Robust Inference for the Cox Proportional Hazards Model , 1989 .

[9]  X. Basagaña,et al.  Differences Between Marginal Structural Models and Conventional Models in Their Exposure Effect Estimates: A Systematic Review , 2011, Epidemiology.

[10]  J. Pearl Invited commentary: understanding bias amplification. , 2011, American journal of epidemiology.

[11]  Brian K. Lee,et al.  Weight Trimming and Propensity Score Weighting , 2011, PloS one.

[12]  P. Gustafson,et al.  Practice of Epidemiology Marginal Structural Cox Models for Estimating the Association Between β-Interferon Exposure and Disease Progression in a Multiple Sclerosis Cohort , 2014 .

[13]  Donald Rubin,et al.  Estimating Causal Effects from Large Data Sets Using Propensity Scores , 1997, Annals of Internal Medicine.

[14]  D. Lio,et al.  Are Endothelial Progenitor Cells the Real Solution for Cardiovascular Diseases? Focus on Controversies and Perspectives , 2015, BioMed research international.

[15]  M. Chandra,et al.  A Marginal Structural Modeling Approach with Super Learning for a Study on Oral Bisphosphonate Therapy and Atrial Fibrillation , 2013 .

[16]  Michal Abrahamowicz,et al.  Comparison of Approaches to Weight Truncation for Marginal Structural Cox Models , 2013 .

[17]  S. Schneeweiss,et al.  Practice of Epidemiology Implications of M Bias in Epidemiologic Studies: a Simulation Study , 2022 .

[18]  P. Gustafson,et al.  Beta‐interferon exposure and onset of secondary progressive multiple sclerosis , 2015, European journal of neurology.

[19]  Cheng Ju,et al.  Using Super Learner Prediction Modeling to Improve High-dimensional Propensity Score Estimation , 2018, Epidemiology.

[20]  Performance of the marginal structural models under various scenarios of incomplete marker's values: A simulation study , 2015, Biometrical journal. Biometrische Zeitschrift.

[21]  Stephen R Cole,et al.  An information criterion for marginal structural models , 2013, Statistics in medicine.

[22]  M. J. van der Laan,et al.  Practice of Epidemiology Improving Propensity Score Estimators ’ Robustness to Model Misspecification Using Super Learner , 2015 .

[23]  Leo Breiman,et al.  Random Forests , 2001, Machine Learning.

[24]  The Impact of Sparse Follow-up on Marginal Structural Models for Time-to-Event Data. , 2015, American journal of epidemiology.

[25]  Romain Neugebauer,et al.  High‐dimensional propensity score algorithm in comparative effectiveness research with time‐varying interventions , 2015, Statistics in medicine.

[26]  P. Gustafson,et al.  Comparison of statistical approaches dealing with time-dependent confounding in drug effectiveness studies , 2018, Statistical methods in medical research.

[27]  Helen Tremlett,et al.  On the application of statistical learning approaches to construct inverse probability weights in marginal structural Cox models: Hedging against weight-model misspecification , 2017, Commun. Stat. Simul. Comput..

[28]  J. Avorn,et al.  Variable selection for propensity score models. , 2006, American journal of epidemiology.

[29]  M. Hernán Invited commentary: hypothetical interventions to define causal effects--afterthought or prerequisite? , 2005, American journal of epidemiology.

[30]  R. Ali,et al.  On computing standard errors for marginal structural Cox models , 2014, Lifetime data analysis.

[31]  Jessica G. Young,et al.  Simulation from a known Cox MSM using standard parametric models for the g‐formula , 2014, Statistics in medicine.

[32]  Trevor Hastie,et al.  Regularization Paths for Generalized Linear Models via Coordinate Descent. , 2010, Journal of statistical software.

[33]  Til Stürmer,et al.  Balancing Automated Procedures for Confounding Control with Background Knowledge , 2014 .

[34]  Patrick J O'Connor,et al.  Super learning to hedge against incorrect inference from arbitrary parametric assumptions in marginal structural modeling. , 2013, Journal of clinical epidemiology.

[35]  P. Gustafson,et al.  Comparison of Statistical Approaches for Dealing With Immortal Time Bias in Drug Effectiveness Studies. , 2016, American journal of epidemiology.

[36]  Karsten M. Borgwardt,et al.  ccSVM: correcting Support Vector Machines for confounding factors in biological data classification , 2011, Bioinform..

[37]  M. E. Karim Causal inference approaches for dealing with time-dependent confounding in longitudinal studies, with applications to multiple sclerosis research , 2015 .

[38]  J Elith,et al.  A working guide to boosted regression trees. , 2008, The Journal of animal ecology.

[39]  J. Robins,et al.  Marginal structural models to estimate the causal effect of zidovudine on the survival of HIV-positive men. , 2000, Epidemiology.

[40]  Michal Abrahamowicz,et al.  Accuracy of Conventional and Marginal Structural Cox Model Estimators: A Simulation Study , 2010, The international journal of biostatistics.

[41]  Jessica G. Young,et al.  Relation between three classes of structural models for the effect of a time-varying exposure on survival , 2010, Lifetime data analysis.

[42]  K. Lapane,et al.  Application of marginal structural models in pharmacoepidemiologic studies: a systematic review , 2014, Pharmacoepidemiology and drug safety.

[43]  David A. Binder,et al.  Fitting Cox's proportional hazards models from survey data , 1992 .

[44]  W G Havercroft,et al.  Simulating from marginal structural models with time‐dependent confounding , 2012, Statistics in medicine.

[45]  Sunduz Keles,et al.  Statistical Applications in Genetics and Molecular Biology Supervised Detection of Conserved Motifs in DNA Sequences with Cosmo , 2011 .

[46]  M. J. van der Laan,et al.  Analysis of longitudinal marginal structural models. , 2004, Biostatistics.

[47]  M. G. Pittau,et al.  A weakly informative default prior distribution for logistic and other regression models , 2008, 0901.4011.

[48]  Peter C. Austin,et al.  Variance estimation when using inverse probability of treatment weighting (IPTW) with survival analysis , 2016, Statistics in medicine.

[49]  S. Cole,et al.  A simulation study of finite‐sample properties of marginal structural Cox proportional hazards models , 2012, Statistics in medicine.

[50]  J. Robins,et al.  Marginal Structural Models to Estimate the Joint Causal Effect of Nonrandomized Treatments , 2001 .

[51]  Stephen R Cole,et al.  Constructing inverse probability weights for marginal structural models. , 2008, American journal of epidemiology.

[52]  S. Cole,et al.  Using marginal structural measurement-error models to estimate the long-term effect of antiretroviral therapy on incident AIDS or death. , 2010, American journal of epidemiology.

[53]  P. Gustafson,et al.  Multiple Sclerosis in Older Adults: The Clinical Profile and Impact of Interferon Beta Treatment , 2015, BioMed research international.

[54]  Peter C Austin,et al.  A comparison of the ability of different propensity score models to balance measured variables between treated and untreated subjects: a Monte Carlo study , 2007, Statistics in medicine.

[55]  Corinna Cortes,et al.  Support-Vector Networks , 1995, Machine Learning.

[56]  Romain Neugebauer,et al.  An application of model-fitting procedures for marginal structural models. , 2005, American journal of epidemiology.

[57]  Geneviève Lefebvre,et al.  Impact of mis‐specification of the treatment model on estimates from a marginal structural model , 2008, Statistics in medicine.

[58]  James M Robins,et al.  Marginal structural models for estimating the effect of highly active antiretroviral therapy initiation on CD4 cell count. , 2005, American journal of epidemiology.

[59]  Susan Gruber,et al.  Ensemble learning of inverse probability weights for marginal structural modeling in large observational datasets , 2015, Statistics in medicine.

[60]  S. Rose Mortality risk score prediction in an elderly population using machine learning. , 2013, American journal of epidemiology.

[61]  James M. Robins,et al.  Marginal Structural Models versus Structural nested Models as Tools for Causal inference , 2000 .

[62]  David A Stephens,et al.  A marginal structural model for multiple‐outcome survival data:assessing the impact of injection drug use on several causes of death in the Canadian Co‐infection Cohort , 2014, Statistics in medicine.