RE: Effectiveness of Pharmaceutical Smoking Cessation Aids in a Nationally Representative Cohort of American Smokers.

We read with interest Leas et al.’s analysis of the Current Population Survey data (1) relating the use of pharmacotherapy to outcome in attempts to quit smoking, particularly as a decade ago we published a similar analysis on some of the same data (2), not cited by Leas et al. We strongly agree with the editorial by Tindle and Greevy that a major issue in the analysis is serious confounding when treatment is assigned clinically or self-selected (3). This is a classic case of the well-known “confounding by indication” (4,5) (or by “severity”) problem, in which treatment is primarily used by those who already have the most severe conditions and are the most prone to poor outcomes. Leas et al. undertook heroic efforts to overcome confounding by propensity score matching, but this is insufficient to remove this bias. Those who are convinced they cannot succeed without treatment (and perhaps whose doctors are also so convinced) are most likely to use it. The limited data available in the survey cannot account for all the factors that may enter into smokers’ assessment of their own prognosis (eg, how motivated they are to quit, how difficult they found quitting last time they tried, what impediments to quitting they expect, etc.). When treatment is actively “assigned” by assessed of risk of failure, the resulting bias is near impossible to correct (5).

Indeed, such bias also affects the relationship between behavioral treatment and outcome. Our 2008 analysis (2), which analyzed some of the same smokers as Leas et al., found that smokers who used behavioral treatment were statistically and clinically significantly less likely to quit than those who did not. And those who used both medication and behavioral treatment did worst of all—worse than those who used only medication. In other words, confounding by indication produces perverse and invalid “findings”—the more treatment, the worse the outcomes. Leas et al. argue that what is needed for medication to succeed is behavioral treatment. Yet they forego examining this premise directly in their analyses, where biasing by indication would likely produce contrary findings. To be clear, we believe that behavioral treatment is effective, including in combination with medication, and have long advocated its use (6). But Leas et al.’s conclusion that medications that have been repeatedly tested and found effective in randomized clinical trials do not work without behavioral treatment is based on fatally confounded data.

Notes

Affiliations of authors: Pinney Associates, Pittsburgh, PA (SS); University of Pittsburgh, Pittsburgh, PA (SS); Pinney Associates, Bethesda, MD (JGG).

PinneyAssociates provides consulting services on tobacco harm minimization (including nicotine replacement therapy and vapor products) to Niconovum USA, RJ Reynolds Vapor Company, and RAI Services Company, all subsidiaries of Reynolds American Inc. SS and JGG also hold a patent for a novel nicotine medication that has not been developed or commercialized.