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Rapid Responses to:
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Electronic letters published:
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Aspirin and NSAIDs for the primary prevention of colorectal cancer - weighting the evidence
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Til Stürmer, M.D., M.P.H. Brigham and Women's Hospital, Harvard Medical School, Julie E. Buring, and Robert J. Glynn
Send rapid response to journal:
til.sturmer{at}post.harvard.edu Til Stürmer, et al.
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The authors of the review papers on aspirin (1) and nonsteroidal anti -inflammatory drugs (NSAIDs) (2) for the primary prevention of colorectal cancer (CRC) ignore important limitations of observational studies, raise concerns unlikely to be valid (1), and fail to include the analysis on NSAIDs from the Physicians' Health Study (PHS) that was published in the time period covered (3). The authors correctly discuss shortcomings of randomized trials showing no protection in men and women, i.e. low dose and short duration (1). They fail, however, to address shortcomings of observational studies on regular long-term drug use, i.e. unmeasured confounding, as an alternative explanation for the reduced risk of CRC observed in most of these studies. Specifically, regular long-term drug use is associated with difficult to measure healthy characteristics. These healthy characteristics of long- term adherers may be associated with reduced risks independent of drug effects as evinced by reduced risks for many adverse outcomes in adherers to placebo. This can lead to paradoxical relations in observational studies (4). To reduce the magnitude of this problem, we excluded regular users of aspirin and NSAIDs from the PHS, thus studying only new regular users, and observed no reduction of CRC risk with aspirin (5) and NSAIDs (3). Unfortunately, the referenced detailed assessment of the quality of each of the studies (1,2) was not available from AHRQ or the authors. However, the authors mentioned concerns about our aspirin analysis in the PHS because of contamination by intervention and a reduced standardized mortality ratio for CRC compared with the U.S. population (1). Randomized aspirin treatment does not threaten the validity of our post-trial study of self-selected aspirin use. Any carry-over of putative aspirin effects would bias the results towards observing a reduced CRC risk in post-trial aspirin users. Reduced standardized morbidity ratios (5) are ubiquitous in volunteer studies and generally do not bias measures of relative risk. Finally, since only three cohort studies of NSAIDs and CRC are included in their analysis (2), the failure to include our observational study on NSAIDs and CRC in the PHS (3) largely reduces the value of the summary estimates. Taken together, we believe that the authors overstate the overall benefits from aspirin (1) and NSAIDs (2) on CRC. Putting greater weight on randomized evidence and observational studies with new- user designs would tip the harm to benefit balance even more towards harm for individuals at average risk for CRC. 1. Dube C, Rostom A, Lewin G, Tsertsvadze A, Barrowman N, Code C, Sampson M, Moher D. The use of aspirin for primary prevention of colorectal cancer: a systematic review prepared for the u.s. Preventive services task force. Ann Intern Med 2007;146:365-75. 2. Rostom A, Dube C, Lewin G, Tsertsvadze A, Barrowman N, Code C, Sampson M, Moher D. Nonsteroidal Anti-inflammatory Drugs and Cyclooxygenase-2 Inhibitors for Primary Prevention of Colorectal Cancer: A Systematic Review Prepared for the U.S. Preventive Services Task Force. Ann Intern Med 2007;146:376-89. 3. Stürmer T, Buring JE, Lee IM, Kurth T, Gaziano JM, Glynn RJ. Colorectal cancer after start of nonsteroidal anti-inflammatory drug use. Am J Med 2006;119:494-502. 4. Glynn RJ, Knight EL, Levin R, Avorn J. Paradoxical relations of drug treatment with mortality in older persons. Epidemiology 2001;12:682- 9. 5. Stürmer T, Glynn RJ, Lee IM, Manson JE, Buring JE, Hennekens CH. Aspirin use and colorectal cancer: post-trial follow-up data from the Physicians' Health Study. Ann Intern Med 1998;128:713-20. Conflict of Interest:None declared |
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