Further investigations of gateway effects using the PATH study

Abstract Background: Considerable interest exists in whether e-cigarette use (“vaping”) by youths increases the risk of initiating cigarette smoking. Based on Waves 1 and 2 of the Population Assessment of Tobacco and Health study we reported that adjustment for propensity for vaping using Wave 1 variables explained about 80% of the unadjusted relationship. This analysis may be over-adjusted had vaping at Wave 1 affected some variables recorded then. Here we present analyses using Waves 1 to 3 to avoid this possibility. Methods: Our main analysis M1 concerned those who had never smoked by Wave 2 and never vaped by Wave 1. Wave 2 vaping was linked to smoking initiation by Wave 3, adjusting for Wave 1 predictors. Sensitivity analyses excluded other tobacco product users at Wave 1, included other tobacco product use as an additional predictor, or were based on propensity for ever smoking or ever any tobacco use, rather than ever vaping. Other analyses adjusted for propensity as derived originally, or ignored Wave 1 data. Other analyses used grouped age (only available originally) or exact age (available now) as a confounder variable, attempted residual confounding adjustment by modifying values of predictor variables using data later recorded, or considered interactions with age. Results: In M1, propensity adjustment removed about 50% of the excess odds ratio (i.e. OR–1), the unadjusted OR, 5.60 (95% CI 4.52-6.93) becoming 3.37 (2.65-4.28), 3.11 (2.47-3.92) or 3.27 (2.57-4.16) depending whether adjustment was for propensity as a continuous variable, as quintiles, or for the 16 variables making up the propensity score. Many factors studied hardly affected the results, including using grouped or exact age, consideration of other tobacco products, including interactions, or using predictors of smoking or tobacco use rather than vaping. The clearest conclusion was that analyses avoiding over-adjustment only explained about 50% of the excess OR whereas analyses subject to over-adjustment explained about 80%. Conclusions: Although much of the unadjusted gateway effect results from uncontrolled confounding, our current analysis provides stronger evidence of a causal effect of vaping than did our earlier analysis. However, some doubts remain about the completeness of confounder adjustment.