Causal inference methods to study gastric tube use in amyotrophic lateral sclerosis

Abstract

Objective: To estimate effects of gastric tube (G-tube) on survival and quality of life (QOL) in people with amyotrophic lateral sclerosis (ALS) correcting for confounding by indication inherent in nonrandomized observational data.

Methods: To complement a recent causal inference analysis, which concluded that G-tube placement increases the hazard of death, permanent assisted ventilation, or tracheostomy by 28%, we fit causal inference models on a different sample of 481 patients with ALS enrolled in a recent clinical trial of ceftriaxone. Forward selection identified predictors of G-tube placement. Effects of G-tube on survival and QOL were estimated using structural nested models and marginal structural models, accounting for predictors of G-tube treatment.

Results: Forced vital capacity and the total score and bulbar subscale of the revised ALS Functional Rating Scale best predicted G-tube placement. Correcting for these confounders, G-tube placement decreased survival time by 46% (p < 0.001) and had no effect on QOL (p = 0.078). Sensitivity survival analyses varied in significance, but none revealed a survival benefit.

Conclusions: In the absence of randomization, causal inference methods are necessary to correct for time-varying confounding. G-tube placement may have a negative effect on survival with no QOL-related benefit for people with ALS. A randomized controlled trial is warranted to further evaluate the efficacy of this widely used intervention.

Clinicaltrialsgov identifier: NCT00349622.

Classification of evidence: This study provides Class III evidence that for patients with ALS, G-tube placement decreases survival time and does not affect QOL.

Figure 1. Counterfactual survival times among gastric tube (G-tube) recipients

Kaplan-Meier curves compare observed survival times in G-tube recipients vs their estimated survival times had they never received a G-tube. Receipt of a G-tube results in 46% shorter survival times (p < 0.001).

Figure 2. Survival after gastric tube (G-tube) placement by American Academy of Neurology guidelines

Kaplan-Meier curves compare survival times among G-tube recipients with forced vital capacity (FVC) <30%, FVC 30%–50%, and FVC >50% at the time of G-tube placement. Lower FVC is associated with poorer survival free of permanent assisted ventilation or tracheostomy after G-tube placement (p < 0.001).

Figure 3. Survival after gastric tube (G-tube) placement by body mass index (BMI) loss from baseline to G-tube placement

Kaplan-Meier curves compare survival times among G-tube recipients with ≥15% loss in BMI from baseline vs stable BMI at the time of G-time placement. Survival free of permanent assisted ventilation or tracheostomy after G-tube placement is not associated with BMI loss (p = 0.464).