title: Direct estimation for adaptive treatment length policies: Methods and application to evaluating the effect of delayed PEG insertion.
abstract: Dysphagia is a primary cause of death among patients diagnosed with amyotrophic lateral sclerosis (ALS), and percutaneous endoscopic gastrostomy (PEG) is a procedure to insert a tube into the stomach to assist or replace oral feeding. It is believed that PEG is beneficial and, generally, earlier insertion is preferable to later. However, gathering clinical evidence to support these beliefs on the use and timing of PEG is challenging because controlled clinical trials are not feasible and clinical endpoints are confounded with PEG in observational data. Moreover, the confounders are time-varying and time to PEG insertion may be only partially observed. We show how one can view this problem as an adaptive treatment length policy and propose a new estimator via g-computation. We show that our estimator is consistent and asymptotically normal for the causal estimand and explore its finite sample properties in simulation studies. Finally, using more than 10 years of data from Emory ALS clinic registry, we found no evidence to suggest that earlier PEG reduced 4-year mortality; thus, our results do not support the hypothesis and belief that initiating palliative care earlier extends life, on average. At the same, we cannot be certain that all important confounding variables are collected and observed to ensure our modeling assumptions are correct, so more work is needed to address these important end-of-life questions for ALS patients.
authors.affiliation: Department of Biostatistics and Programming, Sanofi, Bridgewater, New Jersey 08807, U.S.A.
authors.forename: Xin
authors.initials: X
authors.lastname: Lu
authors.affiliation: Department of Biostatistics and Computational Biology, University of Rochester, Rochester, New York 14642, U.S.A.
authors.forename: Brent A
authors.initials: BA
authors.lastname: Johnson
mesh_terms: D000690:Amyotrophic Lateral Sclerosis; D003680:Deglutition Disorders; D005774:Gastrostomy; D006801:Humans; D011092:Polyethylene Glycols; D012042:Registries
chemical_list: D011092:Polyethylene Glycols
keywords: Competing risks; Dynamic regime; Informative censoring; Structural nested models; g-computation