COX-2 inhibitors and type 4 error
=================================

* Michal R. Pijak
* Frantisek Gazdik

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 Wright´s 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

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    [FREE Full Text](http://www.cmaj.ca/lookup/ijlink/YTozOntzOjQ6InBhdGgiO3M6MTQ6Ii9sb29rdXAvaWpsaW5rIjtzOjU6InF1ZXJ5IjthOjQ6e3M6ODoibGlua1R5cGUiO3M6NDoiRlVMTCI7czoxMToiam91cm5hbENvZGUiO3M6NDoiY21haiI7czo1OiJyZXNpZCI7czo5OiIxNjgvOC85NjAiO3M6NDoiYXRvbSI7czoyMDoiL2NtYWovMTY5LzMvMTkwLmF0b20iO31zOjg6ImZyYWdtZW50IjtzOjA6IiI7fQ==) 

2.  2. Wright JM. The double-edged sword of COX-2 selective NSAIDs. CMAJ 2002;167(10):1131-7. 
    
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8.  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.
    
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9.  9. Mukherjee D, Nissen SE, Topol EJ. Risk of cardiovascular events associated with selective COX-2 inhibitors. JAMA 2001;286:954-9.
    
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12. 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](http://www.bmj.com/cgi/eletters/326/7384/334#30000) (posted 27 Feb 2003; accessed 2003 May 15).