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Previous Volume 341:610-611 August 19, 1999 Number 8 Next

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To the Editor: In their trial of sustained-release bupropion, a nicotine patch, or both for smoking cessation (March 4 issue),¹ Jorenby et al. reach three conclusions. Their first conclusion — that bupropion is an effective treatment for nicotine dependence — is warranted, since previous studies have also found bupropion to be effective.² Their second conclusion is that bupropion plus the nicotine patch produces higher rates of abstinence than the nicotine patch alone, and their third is that bupropion alone produces higher rates of abstinence than the nicotine patch alone. These conclusions are based on the one-year point-prevalence rates of abstinence (i.e., the percentage of subjects who were abstinent at the one-year follow-up assessment). My concern with the last two conclusions is that the one-year point-prevalence rates for the nicotine-patch group and the placebo group were essentially identical (odds ratio=1.1); in other words, although typically efficacious, the nicotine patch was not efficacious with the use of this particular measure in this particular study. Adding any type of therapy that was not efficacious to bupropion therapy would produce the pattern of results reported: treatment with bupropion plus the ineffective therapy would be more effective than bupropion alone, and bupropion alone would be better than the ineffective therapy alone.

Jorenby et al. state that the odds ratios for the comparison between the nicotine patch and placebo were "similar to values reported in previous work" and cite the guidelines of the Agency for Health Care Policy and Research (AHCPR); however, Table 16 of these guidelines lists odds ratios of 2.1 to 2.8 for the nicotine patch.³ In addition, meta-analyses of the use of the nicotine patch under conditions identical to those in the study by Jorenby et al. (minimal intervention or treatment as a part of a family practice) report odds ratios of 2.1⁴ and 3.5.⁵

For some unknown reason, treatments known to be active often perform poorly when used as controls in studies of new treatments.⁶ Unfortunately, the results of neither a study of new and old treatments combined nor a comparison of old and new treatments can be unambiguously interpreted when the old treatment is not efficacious in the study.⁶

In summary, I am not questioning the efficacy of bupropion, but I do believe that we should be cautious in accepting the conclusions of Jorenby et al. with respect to the superiority of combined treatment and the superiority of bupropion over the nicotine patch until replicate studies are conducted in which the nicotine patch is found to be efficacious.

John R. Hughes, M.D.
University of Vermont
Burlington, VT 05401-1419

Editor's note: Dr. Hughes has received consulting fees and grants from many pharmaceutical firms, including Glaxo Wellcome, McNeil, Pharmacia & Upjohn, and SmithKline Beecham.

References

1. Jorenby DE, Leischow SJ, Nides MA, et al. A controlled trial of sustained-release bupropion, a nicotine patch, or both for smoking cessation. N Engl J Med 1999;340:685-691. [Free Full Text]
2. Goldstein MG. Bupropion sustained release and smoking cessation. J Clin Psychiatry 1998;59:Suppl 4:66-72.
3. The Agency for Health Care Policy and Research Smoking Cessation Clinical Practice Guideline. JAMA 1996;275:1270-1280. [Free Full Text]
4. Silagy C, Mant D, Fowler G, Lodge M. Meta-analysis on efficacy of nicotine replacement therapies in smoking cessation. Lancet 1994;343:139-142. [CrossRef][Medline]
5. Fiore MC, Smith SS, Jorenby DE, Baker TB. The effectiveness of the nicotine patch for smoking cessation: a meta-analysis. JAMA 1994;271:1940-1947. [Free Full Text]
6. Clark PI, Leaverton PE. Scientific and ethical issues in the use of placebo controls in clinical trials. Annu Rev Public Health 1994;15:19-38. [CrossRef][Medline]

To the Editor: Dr. Hughes argues that our study does not constitute a good test of the relative efficacy of bupropion and the nicotine patch because the patch produced disappointing results. He argues, in essence, that any interpretation of our results should be deferred because the patch produced atypical effects. Analyses of both the point-prevalence rate and the rate of continuous abstinence indicated the superiority of bupropion. The correct odds ratio for the comparison of the nicotine patch with placebo among subjects with continuous abstinence was 1.8, not 1.1 as reported on page 691 of our paper. According to the AHCPR smoking-cessation guidelines, the size of this effect is typical of that reported in other nicotine-patch studies.¹ Despite the fact that the patch had a fairly typical and significant beneficial effect on the rates of continuous abstinence, bupropion was associated with even better outcomes. The results with respect to point-prevalence outcomes paralleled this differential.

We agree with Dr. Hughes that replication of results is vital. However, we would support this principle just as strongly if the nicotine patch had had better outcomes in our study. Although it is highly tempting to interpret or weight studies according to whether treatments perform in an expected manner, surely this approach would bias science in undesirable ways. We prefer the strategy of accepting our results as they are — recognizing that in the context of this study, bupropion resulted in higher long-term abstinence rates than did placebo or the nicotine patch.

Douglas E. Jorenby, Ph.D.
Michael C. Fiore, M.D., M.P.H.
Timothy B. Baker, Ph.D.
University of Wisconsin Medical School
Madison, WI 53706

References

1. Fiore MC, Bailey WC, Cohen SC, et al. Smoking cessation. Clinical practice guideline no. 18. Rockville, Md.: Agency for Health Care Policy and Research, April 1996. (AHCPR publication no. 96-0692.)

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This article has been cited by other articles:

• Lancaster, T., Stead, L., Silagy, C., Sowden, A. (2000). Regular review: Effectiveness of interventions to help people stop smoking: findings from the Cochrane Library. BMJ 321: 355-358 [Full Text]