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Nicotine replacement therapy (NRT) revisited

Systematic review

One of the interesting aspects of looking at evidence is the effect of time. Initial results for new interventions or observations often look good, but then look less good as more evidence comes in. That is why a degree of caution is sensible. Time can also affect results in the sense that those results may look better or worse as duration of treatment or observation lengthens. Clinical trials have time limits, while clinical practice may have different time horizons.

It behoves us, then, occasionally to revisit the evidence, especially when time is a feature. This has been done with nicotine replacement therapy [1], reminding us that our judgements on efficacy and effectiveness can change with time.

Systematic review

This systematic review of nicotine replacement therapy (NRT) for smoking cessation looked for randomised trials with endpoints beyond 12 months after the start of treatment. It had a terrific search strategy. The aim of trials was permanent cessation of smoking, and required that active and control arms differed only by use of NRT, so allowing supportive advice or counselling at various intensities. Use of any NRT product for any duration was allowed. Information on cessation rates at 12 months and at the longest time afterwards was abstracted.


There were 12 trials with 4,792 patients reporting cessation results at 2-8 years, with a weighted mean of 4.3 years. Trials used nicotine patch, gum, or spray for 3 to 52 weeks, with most using NRT for 12 weeks or longer (weighted mean 22 weeks). All but one of the trials assessed smoking cessation by breath carbon monoxide or urine cotinine measurement. Trials predominantly excluded light smokers of fewer than 10-15 cigarettes daily. Support and advice on cessation was of varying intensity.

Figure 1 shows smoking cessation results of the individual trials at the longest time. Most of the trials were small, with two contributing over 2,600 patients, and having low quit rates with both NRT and placebo.

Figure 1: Smoking cessation rates at longest study duration with NRT and placebo

Table 1 shows quit rates and derived statistics for the trials both at 12 months and at the longest duration. The proportion of patients who were non-smokers fell between 12 months and the longest duration, as previous quitters began smoking again. A third of quitters had begun to smoke again (Figure 2) after both NRT and placebo. Figure 3 shows the results for 24 individual treatment arms of the 12 trials.

Table 1: Results of trials at 12 months and at longest duration

Percent stopped smoking
Duration of observation
Relative risk
(95% CI)
(95% CI)
12 months
1.8 (1.6 to 2.1)
12 (10 to 16)
1.7 (1.5 to 2.1)
19 (15 to 28)

Figure 2: Smoking cessation rates at 12 months and at longest study duration

Figure 3: Percentage of quitters at 12 months smoking again at longest duration

This adversely affected the efficacy of NRT as measured by the number needed to treat (Table 1). NRT rather than placebo would have to be used in 12 patients to induce one more patient to quit smoking at 12 months. But NRT would have to be used in 19 patients for one more to be a non-smoker after an average of 4.3 years.


NRT has clear efficacy in helping some patients stop smoking over the short term. The effectiveness of NRT is eroded by the propensity of former smokers to begin smoking again. This study showed that at least a third of quitters began to smoke again after NRT or placebo.

In the case of NRT the argument of cost effectiveness is governed by how many people stop smoking because of NRT. At 12 months, after an average of 22 weeks of NRT treatment, the answer is 1 patient in 12. But at longer follow up, it is more like 1 in 19.

The real importance of this study is not, however, about smoking cessation, but about how duration of observation can effect how we perceive a result. In this case, there is an argument that an intervention that looks just about useful after one year, is tipping towards irrelevance by four.

What this does is to open something of a Pandora's box of cost effectiveness. If the effect of NRT in smoking cessation continues to diminish as recidivist quitters begin to smoke again, does the cost of the effort outweigh the health gains? It may just be easier to ban smoking in public places. In California, where bans began, smoking rates have halved.


  1. J Etter, JA Stapleton. Nicotine replacement therapy for long-term smoking cessation: a meta-analysis. Tobacco Control 2006 15: 280-285.

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