title: Collaborative targeted maximum likelihood estimation for variable importance measure: Illustration for functional outcome prediction in mild traumatic brain injuries.
abstract: Standard statistical practice used for determining the relative importance of competing causes of disease typically relies on ad hoc methods, often byproducts of machine learning procedures (stepwise regression, random forest, etc.). Causal inference framework and data-adaptive methods may help to tailor parameters to match the clinical question and free one from arbitrary modeling assumptions. Our focus is on implementations of such semiparametric methods for a variable importance measure (VIM). We propose a fully automated procedure for VIM based on collaborative targeted maximum likelihood estimation (cTMLE), a method that optimizes the estimate of an association in the presence of potentially numerous competing causes. We applied the approach to data collected from traumatic brain injury patients, specifically a prospective, observational study including three US Level-1 trauma centers. The primary outcome was a disability score (Glasgow Outcome Scale - Extended (GOSE)) collected three months post-injury. We identified clinically important predictors among a set of risk factors using a variable importance analysis based on targeted maximum likelihood estimators (TMLE) and on cTMLE. Via a parametric bootstrap, we demonstrate that the latter procedure has the potential for robust automated estimation of variable importance measures based upon machine-learning algorithms. The cTMLE estimator was associated with substantially less positivity bias as compared to TMLE and larger coverage of the 95% CI. This study confirms the power of an automated cTMLE procedure that can target model selection via machine learning to estimate VIMs in complicated, high-dimensional data.
authors.affiliation: 1 Department of Anesthesia and Perioperative Care, UCSF, San Francisco General Hospital, San Francisco, CA, USA.
authors.forename: Romain
authors.initials: R
authors.lastname: Pirracchio
authors.affiliation: 2 Brain and Spinal Injury Center, San Francisco, CA, USA.|3 Department of Neurosurgery, University of California San Francisco, San Francisco, CA, USA.
authors.forename: John K
authors.initials: JK
authors.lastname: Yue
authors.affiliation: 2 Brain and Spinal Injury Center, San Francisco, CA, USA.|3 Department of Neurosurgery, University of California San Francisco, San Francisco, CA, USA.
authors.forename: Geoffrey T
authors.initials: GT
authors.lastname: Manley
authors.affiliation: 4 Division of Biostatistics, School of Public Health, University of California Berkeley, Berkeley, CA, USA.
authors.forename: Mark J
authors.initials: MJ
authors.lastname: van der Laan
authors.affiliation: 4 Division of Biostatistics, School of Public Health, University of California Berkeley, Berkeley, CA, USA.
authors.forename: Alan E
authors.initials: AE
authors.lastname: Hubbard
mesh_terms: D000070642:Brain Injuries, Traumatic / Q000503:physiopathology*; D003299:Cooperative Behavior; D005544:Forecasting; D023261:Glasgow Outcome Scale; D006801:Humans; D016013:Likelihood Functions; D000069550:Machine Learning; D017063:Outcome Assessment, Health Care / Q000379:methods; D020127:Recovery of Function
keywords: Variable importance measure; causal inference; collaborative targeted maximum likelihood; high-dimensional data; positivity; semi-parametric