Further investigation of gateway effects using the PATH study

Background: Interest exists in whether youth e-cigarette use ("vaping") increases risk of initiating cigarette smoking. Using Waves 1 and 2 of the US PATH study we previously reported adjustment for vaping propensity using Wave 1 variables explained about 80% of the unadjusted relationship. Here data from Waves 1 to 3 are used to avoid over-adjustment if Wave 1 vaping affected variables recorded then. Methods: Main analyses M1 and M2 concerned Wave 2 never smokers who never vaped by Wave 1, linking Wave 2 vaping to Wave 3 smoking initiation, adjusting for predictors of vaping based on Wave 1 data using differing  propensity indices.  M3 was similar but derived the index from Wave 2 data.  Sensitivity analyses excluded Wave 1 other tobacco product users, included other product use as another predictor, or considered propensity for smoking or any tobacco use, not vaping. Alternative analyses used exact age (not previously available) as a confounder not grouped age, attempted residual confounding adjustment by modifying predictor values using data recorded later, or considered interactions with age. Results: In M1, adjustment removed about half the excess OR (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 the variables making up the propensity score. Many factors had little effect: using grouped or exact age; considering other products; including interactions; or using predictors of smoking or tobacco use rather than vaping. The clearest conclusion was that analyses avoiding over-adjustment explained about half the excess OR, whereas analyses subject to over-adjustment explained about 80%. Conclusions: Although much of the unadjusted gateway effect results from confounding, we provide stronger evidence than previously of some causal effect of vaping, though doubts still remain about the completeness of adjustment.