Measures and predictors of varenicline adherence in the treatment of nicotine dependence

Abstract

Introduction While adherence to medication in smoking cessation clinical trials is strongly associated with clinical outcome, very few studies have evaluated the validity of pill count as a measure of adherence relative to a biological assay, and evaluated a broad range of correlates of adherence. Methods In a smoking cessation clinical trial of varenicline, we compared pill counts collected over 4 different time periods to varenicline salivary levels taken after 2 weeks of treatment, as well as evaluated predictors of adherence to varenicline. Results Using a binary measure of adherence based on salivary varenicline levels, adherence was higher among older, white, and more educated participants. Relative to 3, 7, and 14-day pill count, 12-week pill count was the only significant measure able to discriminate adherence as defined by salivary varenicline levels (assessed by area under the receiver operating characteristic curve; AUC = .59, p =.004). Seventy-two percent of participants who indicated adherence on 12-week pill count were classified as adherent based on varenicline saliva levels (sensitivity=.80; specificity=.40). There was modest variability in the relationship between 12-week pill count and varenicline levels across race and rate of nicotine metabolism. Lastly, General Estimating Equation models demonstrated that longitudinal changes in withdrawal, craving, negative and positive affect, and side effect count and severity were not related to adherence based on salivary varenicline levels. Conclusions These results indicate that 12-week pill count was the best, albeit a relatively weak, measure of varenicline adherence; additional factors associated with treatment adherence need to be identified.

The association between self-reported varenicline adherence and varenicline blood levels in a sample of cancer patients receiving treatment for tobacco dependence

“…Varenicline is one of the most effective medications for tobacco dependence ( Cahill, Stevens, Perera, & Lancaster, 2013 ) even among smokers with psychiatric ( Anthenelli et al, 2016 ) and medical ( Price et al, 2017 ) comorbidities. However, in general population clinical trials, adherence to varenicline rarely exceeds 60% (e.g., Peng et al, 2017 ), with little known about adherence rates in populations with comorbidities ( Pacek, McClernon, & Bosworth, 2017 ). Across numerous studies, suboptimal adherence significantly reduces the likelihood of successful quitting ( Pacek et al, 2017 ; Peng et al, 2018 ).…”

“…Despite numerous clinical studies of varenicline, the literature has relied upon self-reported pill count data to determine varenicline adherence with only two exceptions ( Buchanan et al, 2012 ; Peng et al, 2017 ). Unfortunately, self-reported pill count data are susceptible to response bias and misreporting, which can overestimate adherence ( Dunbar-Jacob & Rohay, 2016 ).…”

A randomized controlled trial of 24 weeks of varenicline for tobacco use among cancer patients: Efficacy, safety, and adherence

“…However, this is one of the largest smoking cessation trials conducted with cancer patients. Lastly, adherence to varenicline was low, even vs the general population where it is typically 50% to 60% . With more than half the sample taking less than 80% of the prescribed medication, the therapeutic effect of varenicline was limited, which may have diminished long‐term cessation.…”

“…Lastly, adherence to varenicline was low, even vs the general population where it is typically 50% to 60%. 39,40 With more than half the sample taking less than 80% of the prescribed medication, the therapeutic effect of varenicline was limited, which may have diminished long-term cessation. The complexity and intensity of ongoing medical care for patients may have posed particular challenges for treatment engagement and future studies are needed to develop and test novel approaches for increasing treatment adherence.…”

Impact of early nausea on varenicline adherence and smoking cessation

“…Nausea severity data were collected through self-report at multiple time-points in the Quit2Live (weeks 1, 4 and 8) and PNAT (weeks 1 and 2) trials; nausea was examined on a 4-point scale (0-3), as previously described in varenicline randomized clinical trials [17][18][19][20][21][22][23][24][25][26]. Adherence was biologically assessed at weeks 4 (Quit2Live, plasma sample) and 2 (PNAT, saliva sample) using varenicline concentrations analyzed by LC-MS/MS (limit of quantification = 0.05 ng/ml for plasma, 1 ng/ml for saliva) [6,27,28]. Adherence was determined based on varenicline concentrations instead of self-report pill counts, as the varenicline concentrations were more predictive of cessation outcomes, while self-report pill counts tended to over-estimate adherence and were less predictive of cessation outcomes [6,7,29].…”