presents the importance scores for the combined mono and combination therapies for the Effectiveness and Efficacy trials. These plots rank order the variables in terms of their importance in the prediction of outcomes (i.e., smoking vs. abstinence at 8-week post-TQD) for each treatment; this is reflected by the length of its value along the horizontal axis. The plots were very similar when individual treatments were examined within the monotherapies and within the combination pharmacotherapies. However, different variables assumed predictive importance across the monotherapy and combination therapy conditions. For instance, for all monotherapy conditions in the Effectiveness trial, the important predictors (statistically significant, indicated by gray bars) included FTND6 and the FTND TOTAL SCORE. In the Efficacy Trial, the important predictors for the monotherapy conditions included FTND1, FTND TOTAL SCORE, CIGARETTES/DAY, FTND4, FTND2, FTND6, and MOST CIGARETTES/DAY (see for item definitions). Similar results were obtained for the NRT monotherapy conditions (i.e., lozenge alone, patch alone) in both the Effectiveness and Efficacy trials (). This led to the prediction that smokers who were low versus high in dependence might be better aided by monotherapy.
Figure 1. Importance scores for the all monotherapies and all combination treatment groups in the Effectiveness and Efficacy trials. Gray bars indicate that the importance scores of the variables are statistically significant in predicting follow-up smoking 8 weeks (more ...)
Figure 2. Importance scores for mono NRT and combination nicotine replacement therapy (NRT) in the Efficacy and Effectiveness trials. Gray bars indicate that the importance scores of the variables are statistically significant in predicting follow-up smoking 8 (more ...)
For the combination therapy conditions, the dependence variables were less predictive of outcomes than they were for the monotherapy conditions. In neither the Effectiveness nor the Efficacy Trial did any dependence variable significantly predict outcomes in the combination conditions (). Instead, in these conditions, outcomes were most consistently predicted by life context and demographic factors such as smokers in the person’s life, marital status, income, and smoking restrictions. A similar pattern was seen in both trials when only combination NRT was examined (). However, life context and demographic variables were not as consistently predictive of outcomes in the combination NRT condition in the Effectiveness trial as in the Efficacy trial. This whole pattern of findings led to a prediction that people, low in dependence but with significant life context risk (i.e., a spouse who smokes) would not benefit greatly from combination pharmacotherapy.
Inspection of the importance scores suggested several variables that might be effective for identifying who is and who is not helped by combination therapy relative to monotherapy (FTND TOTAL SCORE, FTND1, FTND2, and MOST CIGARETTES/DAY as measures of nicotine dependence, and SPOUSE SMOKES and LONGEST PRIOR QUIT ATTEMPT as measures of other risk). Comparisons of the leading candidate predictors over the two trials implicated two variables as the strongest predictors: FTND1 and SPOUSE SMOKES. and show how these variables predict smoking at 8-week post-TQD for the different treatment conditions in both trials.
Sample Sizes, Follow-up Smoking Rates (SEs in parentheses), and Relative Risks for Monotherapy and Combination Pharmacotherapy Conditions in the Effectiveness Trial
shows sample sizes, 8-week smoking outcomes, and the relative risks of smoking at 8 weeks in the Effectiveness trial when using FTND1 and the SPOUSE SMOKES (context exposure) variables to categorize relapse risk. The relative risk of smoking is the smoking rate observed in the combination therapy cell divided by the smoking rate in the corresponding monotherapy cell. The dichotomous measurement of the SPOUSE SMOKES item makes its scoring straightforward. FTND1 has four response options (); the decision tree analytic strategy identified a cutscore of smoking within the first 5 min of waking versus a longer smoking latency, as providing the most efficient prediction of 8-week smoking outcomes. Therefore, all analyses involving FTND1 used this cutscore (i.e., response option 1 vs. 2–4). shows that risk of 8-week smoking generally is lower among all individuals receiving combination therapy: ranging from 68% to 80% in the monotherapy conditions and between 50% and 60% in the combination pharmacotherapy conditions, across the four cells yielded by crossing FTND1 and SPOUSE SMOKES. The rate of smoking was significantly lower in the combination pharmacotherapy condition than in the monotherapy conditions in three of the four cells. In fact, smoking rates were about 20 percentage points higher in the monotherapy cells with one exception—the cell constituted by smokers with low-dependence (low FTND1 score) and high-context exposure (a spouse who smokes), which produced a nonsignificant difference between the smoking rates for the monotherapy condition (71%) and the combination conditions (60%).
also displays relative risk of 8-week smoking between the monotherapy and combination therapy conditions for the four cells constituted by the crossing of SPOUSE SMOKES and FTND1. shows that in the Effectiveness trial, 8-week smoking rates among those using combination therapy were only about 72%–75% of what they were among those getting monotherapy, except for individuals with low FTND1 scores and high-context exposure: the combination therapy smoking rates were 85% of those produced by monotherapy. Thus, there was some benefit to receiving combination therapy in all cells, but the effect was smaller and nonsignificant among individuals with low FTND1 scores and high-context exposure.
The same analyses were conducted using only the NRT treatments and produced results essentially the same as when all treatment conditions were used in analyses (i.e., ). Again, combination therapy produced generally lower 8-week smoking rates than monotherapy. Further, as is the case in the All Mono and All Combo comparisons, the discrepancy in smoking rates between monotherapy and combination NRT conditions is significant in all cells except that of the combination of high-context exposure and low FTND1 scores. The relative 8-week smoking risk was 86% in individuals receiving combination NRT versus monotherapy NRT in this cell and ranged from 72% to 77% in the other three cells.
The Effectiveness Trial data showed that combination pharmacotherapy produced significantly better results in most smokers, except those who were low in nicotine dependence and who lived with a spouse who smokes.
For the Efficacy Trial, shows the sample sizes, 8-week smoking rates, and relative risks of smoking when using dependence (FTND1) and the context exposure (SPOUSE SMOKES) variables to categorize smoking risk. shows that, as in the Effectiveness analyses, the rate of smoking was significantly lower in the All Combo condition versus the All Mono condition in only three of the four cells constituted by the crossing of the FTND1 and context exposure variables. For instance, when subjects had a low FTND1 score and low-context exposure, 53% were smoking by 8 weeks among those receiving one of the monotherapies compared with only 42% in comparable cells in the combination therapy condition. However, among subjects who had low FTND1 scores and high-context exposure, 58% were smoking if given monotherapy and 56% were smoking if given combination therapy. Relative risk data also showed that combination pharmacotherapy benefitted all groups except those with low FTND1 scores and high-context exposure. The Efficacy trial also comprised a placebo control group. This group was smaller in size than the pharmacotherapy conditions by design (n = 188), conferring little power for statistical comparisons. However, this group showed a risk pattern similar to that of the monotherapy participants, with high FTND1 scores predicting a greater risk of 8-week smoking than was found in the low-dependence group (78% vs. 66%).
The same analyses were conducted in the Efficacy sample using only the NRT treatments. These analyses showed that combination therapy generally produced lower 8-week smoking rates than did monotherapy. However, in the Efficacy trial, the smoking rate was higher in individuals with low FTND1 scores and high-context exposure who received combination NRT versus monotherapy NRT (i.e., 61% vs. 55%); thus, the relative risk of smoking was 111% in the combination NRT subjects versus the monotherapy NRT subjects in the low-dependence/high-context exposure cell.
The decision utility of the dependence (FTND1) and life context (SPOUSE SMOKES) variables for treatment assignment involved comparing 8-week smoking rates in the Effectiveness trial (where prediction effects were weaker than in the Efficacy trial) under conditions of equal selection ratios (equal assignment rates to the monotherapy and combination therapy conditions) with the rates of 8-week smoking obtained when smokers high in context and low in dependence were assigned to monotherapy. The smoking rate under a condition of random assignment would be about 54% across the total sample; the rate would be about 49% using the algorithm. Finally, the pattern of data in the two studies implies an interaction between combination therapy responder group (nonresponders being those low in dependence and having a smoking spouse) and combination versus monotherapy condition. This interaction was significant via logistic regression when the trials were merged (Wald = 4.13; p = .04) and in the Efficacy trial (Wald = 4.3; p = .03) but not in the Effectiveness trial (Wald = .98; p = .30).