The purpose of this review is to investigate whether over-the-counter (OTC) nicotine replacement therapy (NRT) is “effective.” Effectiveness is usually defined as showing a treatment effect in a study with high external validity, that is, a study that uses a relatively unselected sample and employs treatment under the conditions in which a treatment is intended to be used (Gartlehner, Hansen, Nissman, Lohr, & Carey, 2006
; Nash, McCrory, Nicholson, & Andrasik, 2005
; Prochaska, Evers, Prochaska, Van Marter, & Johnson, 2007
). In contrast, efficacy is usually defined as showing a treatment effect in a study with high internal validity, that is, a study that uses highly motivated participants, standardized treatment protocols, and under an ideal highly controlled research environment (Gartlehner et al., 2006
; Nash et al., 2005
; Prochaska et al., 2007
Based on over 100 randomized controlled trials (RCTs) of over 40,000 participants, all meta-analyses in the last five years have concluded that all NRTs are efficacious; typically, odds ratios (OR
s) for NRT in these meta-analyses are 1.5–2.0 (Hughes, 2009
). Most of the NRTs (nicotine gum, inhaler, nasal spray, lozenge, microtab, and patch) were initially marketed as prescription (Rx) medications; however, when it became clear that having to see a physician was a barrier to access to NRT (Shiffman & Sweeney, 2007
), almost all were approved for OTC sale. Currently, OTC NRT is, by far, the most widely used treatment for smoking cessation. In the United States, one third of those who try to stop smoking use OTC NRT (Shiffman, Brockwell, Pillitteri, & Gitchell, 2008b
Several medications that were efficacious in RCTs appear to not be effective when used in real-world settings (Walsh, 2008
). With NRT, the absence of professional advice, the inclusion of less-motivated smokers or poor compliance, might undermine NRT effectiveness (Walsh, 2008
). The optimal way to test effectiveness is via prospective controlled trials in effectiveness settings. Several controlled trials examined NRT in OTC-like settings (e.g., store-front settings with no advice given). Our meta-analysis of these trials concluded that OTC NRT was effective (Hughes, Shiffman, Callas, & Zhang, 2003
); however, the number of OTC trials in our analysis was small (n
= 7) and some used nonrandomized designs.
Although RCTs in real-world situations are the most valid measure of effectiveness, volunteer bias may still occur (Amori & Lenox, 1989
) plus the monitoring and structure of a RCT could influence results. Several nonrandomized studies have been reported, and their results could provide a different test of the effectiveness of OTC NRT. The two designs used have been retrospective cohort, and pre- versus post-studies. Retrospective cohort studies have compared the abstinence rates of those who chose to use OTC NRT on a quit attempt with those who chose not to do so with the null hypothesis of no difference in successful cessation in the two groups. These studies have been done with convenience and population-based samples. In this review, we have also included retrospective cohort studies that used samples from quitlines and in-person treatments that provided free OTC NRT. These are less-valid tests of effectiveness because, although not documented, it is likely the treatments gave advice about use of NRT and thus have some Rx features to them. Nevertheless, for completeness, we include their results.
One asset of retrospective cohort studies is that their samples usually are more externally valid than those of the RCTs, that is, most retrospective cohort samples have few inclusion criteria and most are of smokers not enrolled in a formal treatment program. The major liability to retrospective cohort studies is that smokers self-select into these groups. Several lines of evidence indicate smokers who choose to use NRT are different than those who choose not to use NRT (Shiffman, Brockwell, Pillitteri, & Gitchell, 2008a
). It is an almost universal finding that those with more severe illnesses are more likely to seek treatment; these phenomena have been labeled “indication bias” (Shiffman et al., 2008a
). In fact, NRT users are heavier and more dependent smokers and have had more difficulty quitting in the past (Shiffman, Di Marino, & Sweeney, 2005
). Retrospective cohort studies attempt to correct for such “confounds” by using post-hoc covariates, but most of these studies come from surveys in which there is limited information on the relevant confounds. Another problem is that most retrospective cohort studies use retrospective recall to assess quit attempts, which can be biased. For example, smokers forget many quit attempts (Berg et al., 2010
; Gilpin & Pierce, 1994
), and they may be more likely to recall treatments in which NRT was used than in those in which it was not used.
Other studies have compared abstinence rates between Rx NRT and OTC NRT periods, which we will label “pre- versus post-studies” (Campbell & Stanley, 1966
). These studies are typically population surveys that test whether quit rates were similar in the OTC and Rx periods. Like the retrospective cohort studies, the pre- versus post-studies should have more externally valid samples than efficacy trials. Their major liabilities are the self-selection bias described above plus historical confounds (Shiffman et al., 2008a
). For example, if the population of smokers is “hardening” over time, that is, as prevalence of smoking falls, remaining smokers are those who are more dependent, have more problems of living, etc (Warner & Burns, 2003
), this could falsely lower OTC quit rates compared with Rx NRT quit rates.
We have included studies of quitlines in pre- versus post-studies. Even though these studies did not directly test OTC NRT, they do report quit rates when the quitlines did not provide free NRT and then after they did so (the latter always occurred during the OTC period). Thus, if OTC NRT is not effective, then the quit rates before and after free NRT should be identical. This is probably the weakest test of OTC NRT for two reasons. First, as mentioned above, quitlines may have given advice on use of NRT and thus did not differ substantially from prescription (Rx) NRT. Second, it is likely highly dependent smokers were not willing to call a quitline when no NRT was offered but decided to attend when they heard free NRT was available.
Importantly, a few of the studies also reported not only just on the effectiveness of OTC NRT but also on the effectiveness of Rx medications and counseling (Fiore et al., 2000
) and, thus, can be used to assess the specificity of any negative results. For example, assume OTC NRT users have quit rates similar to that in nonusers. If, in that same study, counseling was found effective, this would suggest a true negative result for OTC NRT. If, on the other hand, counseling was also not found effective, then (if one believes quitlines are truly effective treatments) this result would suggest the study methods were insensitive to detect changes in quit rates due to use of treatment.