title: Advanced statistical methods to study the effects of gastric tube and non-invasive ventilation on functional decline and survival in amyotrophic lateral sclerosis.
abstract: A few studies suggest that non-invasive ventilation (1) and gastric tube (G-tube) may have a positive impact on survival but the effect on functional decline is unclear. Confounding by indication may have produced biased estimates of the benefit seen in some of these retrospective studies. The objective of this study was to evaluate the effects of G-tube and NIV on survival and functional decline using advanced statistical models that adjust for confounding by indications. A database of 331 subjects enrolled in previous clinical trials in ALS was available for analysis. Marginal structural models (MSM) were used to compare the mortality hazards and ALSFRS-R slopes between treatment and non-treatment groups, after adjusting for confounding by indication. Results showed that the placement of a G-tube was associated with an additional 1.42 units/month decline in the ALSFRS-R slope (p < 0.0001) and increased mortality hazard of 0.28 (p = 0.02). The use of NIV had no significant effect on ALSFRS-R decline or mortality. In conclusion, marginal structural models can be used to adjust for confounding by indication in retrospective ALS studies. G-tube placement could be followed by a faster rate of functional decline and increased mortality. Our results may suffer from some of the limitations of retrospective analyses.
authors.affiliation: Massachusetts General Hospital, Harvard Medical School, USA. NATASSI@PARTNERS.ORG
authors.forename: Nazem
authors.initials: N
authors.lastname: Atassi
authors.forename: Merit E
authors.initials: ME
authors.lastname: Cudkowicz
authors.forename: David A
authors.initials: DA
authors.lastname: Schoenfeld
mesh_terms: D000690:Amyotrophic Lateral Sclerosis / Q000503:physiopathology* / Q000628:therapy*; D002986:Clinical Trials as Topic; D003627:Data Interpretation, Statistical; D016208:Databases, Factual; D018450:Disease Progression; D004750:Enteral Nutrition; D006801:Humans; D011175:Positive-Pressure Respiration; D012189:Retrospective Studies; D016019:Survival Analysis