This Article
Right arrow Full Text (PDF)
Right arrow Submit a response
Right arrow Alert me when this article is cited
Right arrow Alert me when eLetters are posted
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Pijak, M. R.
Right arrow Articles by Gazdik, F.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Pijak, M. R.
Right arrow Articles by Gazdik, F.
Related Collections
Right arrow Drugs: gastrointestinal system
Right arrow Competing interests, conflicts of interest
CMAJ • August 5, 2003; 169 (3)
© 2003 Canadian Medical Association or its licensors

Letters
Correspondance

COX-2 inhibitors and type 4 error

Michal R. Pijak{dagger} and Frantisek Gazdik{ddagger}

{dagger}Consultant Rheumatologist, Department of Clinical Immunology, Institute of Preventive and Clinical Medicine, Bratislava, Slovakia; {ddagger}Research Fellow, Department of Clinical Immunology, Institute of Preventive and Clinical Medicine, Bratislava, Slovakia

Further to Walter Maksymowych's letter1 about James Wright's article on cyclooxygenase-2 (COX-2) inhibitors,2 we would like to add that disclosure of competing interests and presentation of contrary viewpoints tend to reduce the likelihood of bias contributing to the "tomato effect," also known as type 4 error. This type of error is an overestimation of risks, which leads to rejection of an efficacious therapy.3

Concerns about the possibility of type 4 error in this case are reinforced by a summary of the Wright article published recently in BMJ,4 which states that "This is an excellent (although non-systematic) review of the benefits and harms of COX-2 inhibitors." It has been overlooked that Wright, in disregarding systematic reviews and meta-analyses on COX-2 inhibitors, has missed a large body of relevant evidence, including differences between individual NSAIDs.5,6,7,8

Before the publication of Wrights article, several other authors presented critical views regarding the cardiovascular safety of COX-2 inhibitors under the guise of scientific objectivity.9,10,11 Some argued that use of acetylsalicylic acid (ASA) might change the cost-effectiveness of COX-2 inhibition by reducing gastrointestinal benefit; hence, there would be no justification for prescribing a more expensive therapy.11 However, these authors overlooked the benefits of the combination of ASA and COX-2 inhibition relative to less-expensive options such as ASA combined with a non-ASA NSAID or a non-ASA NSAID alone. These benefits include better gastrointestinal tolerability, sustained inhibition of platelet aggregation and freedom in the dosing regimen.12

Michal R. Pijak Consultant Rheumatologist Frantisek Gazdik Research Fellow Department of Clinical Immunology Institute of Preventive and Clinical Medicine Bratislava, Slovakia

References

  1. Maksymowych WP. Seeking disclosure [letter]. CMAJ 2003;168(8):960,962. [Free Full Text]
  2. Wright JM. The double-edged sword of COX-2 selective NSAIDs. CMAJ 2002;167(10):1131-7. [Abstract/Free Full Text]
  3. Robin ED, Lewiston NJ. Type 3 and type 4 errors in the statistical evaluation of clinical trials. Chest 1990;98:463-5.[Free Full Text]
  4. Harms outweigh benefits of COX 2 for many patients [filler]. BMJ 2003;326(7389):0. Available: www.bmj.com/cgi/content/full/326/7389/0/f (accessed 2003 May 15).
  5. Reicin AS, Shapiro D, Sperling RS, Barr E, Yu Q. Comparison of cardiovascular thrombotic events in patients with osteoarthritis treated with rofecoxib versus nonselective nonsteroidal anti-inflammatory drugs (ibuprofen, diclofenac, and nabumetone). Am J Cardiol 2002;89:204-9.[Medline]
  6. White WB, Faich G, Whelton A, Maurath C, Ridge NJ, Verbug KM, et al. Comparison of thromboembolic events in patients treated with celecoxib, a cyclooxygenase-2 specific inhibitor, versus ibuprofen or diclofenac. Am J Cardiol 2002; 89:425-30.[Medline]
  7. Zhao SZ, Reynolds MW, Lejkowith J, Whelton A, Arellano FM. A comparison of renal-related adverse drug reactions between rofecoxib and celecoxib, based on the World Health Organization/Uppsala Monitoring Centre safety database. Clin Ther 2001;23:1478-91.[Medline]
  8. Whelton A, Fort JG, Puma JA, Normandin D, Bello AE, Verburg KM. Cyclooxygenase-2-specific inhibitors and cardiorenal function: a randomized controlled trial of celecoxib and rofecoxib in older hypertensive osteoarthritis patients. Am J Ther 2001;8:85-95.[Medline]
  9. Mukherjee D, Nissen SE, Topol EJ. Risk of cardiovascular events associated with selective COX-2 inhibitors. JAMA 2001;286:954-9.[Abstract/Free Full Text]
  10. Wooltorton E. What's all the fuss? Safety concerns about COX-2 inhibitors rofecoxib (Vioxx) and celecoxib (Celebrex). CMAJ 2002;166 (13): 1692-3. [Free Full Text]
  11. Pickard AS, Schumock GT. Aspirin use may change cost-effectiveness of COX-2 inhibitors. Arch Intern Med 2002;162:2637-8. [Free Full Text]
  12. Pijak MR, Gazdik F. The overlooked benefits of aspirin-COX-2 inhibitor combination for patients with cardiovascular risk [electronic letter]. Available: www.bmj.com/cgi/eletters/326/7384/334#30000 (posted 27 Feb 2003; accessed 2003 May 15).



This article has been cited by other articles:


Home page
 CMAJHome page
M. R. Pijak, I. Huzicka, and F. Gazdik
Coxibs and cardiovascular risk
Can. Med. Assoc. J., October 11, 2005; 173(8): 852 - 852.
[Full Text] [PDF]

This Article
Right arrow Full Text (PDF)
Right arrow Submit a response
Right arrow Alert me when this article is cited
Right arrow Alert me when eLetters are posted
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Pijak, M. R.
Right arrow Articles by Gazdik, F.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Pijak, M. R.
Right arrow Articles by Gazdik, F.
Related Collections
Right arrow Drugs: gastrointestinal system
Right arrow Competing interests, conflicts of interest