Channelling of patients taking NSAIDs or cyclooxygenase-2-specific inhibitors and its effect on interpretation of outcomes.
When new drugs with improved safety or efficacy are introduced, they may be preferentially prescribed to specific populations of patients. Safety and efficacy may be underestimated if such channelling effects are not recognized. Meloxicam and cyclooxygenase (COX)-2-specific inhibitors were developed as safer alternatives to non-steroidal anti-inflammatory drugs (NSAIDs) for the treatment of osteoarthritis and rheumatoid arthritis. Studies of the use of meloxicam and COX-2-specific inhibitors demonstrate that both of these drugs are being prescribed to patients at increased risk of gastrointestinal adverse drug events. In the case of COX-2-specific inhibitors, this channelling appears to represent a prescribing pattern consistent with current recommendations. Subsequent analysis of the data, after adjusting for channelling bias, showed that the risk of gastrointestinal toxicity for meloxicam was similar to that for other NSAIDs, while COX-2-specific inhibitors reduced the risk of developing gastrointestinal adverse drug events by approximately 60%. These studies serve as examples of observed channelling bias and highlight the need for adjusting for channelling in order to provide a valid assessment of relevant outcomes for drugs likely to be preferentially prescribed to specific populations.
Department of Clinical Pharmacology and Therapeuitcs, Ninewells Hospital and Medical School, Dundee, UK. t.m.macdonald@dundee.ac.uk
T M
TM
MacDonald
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D
Pettitt
F H
FH
Lee
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JS
Schwartz
D000368:Aged; D000369:Aged, 80 and over; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000009:adverse effects*; D001172:Arthritis, Rheumatoid / Q000188:drug therapy; D051546:Cyclooxygenase 2; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors / Q000009:adverse effects*; D004363:Drug Utilization; D005260:Female; D005767:Gastrointestinal Diseases / Q000139:chemically induced*; D006801:Humans; D007527:Isoenzymes / Q000037:antagonists & inhibitors*; D008297:Male; D000077239:Meloxicam; D008565:Membrane Proteins; D010003:Osteoarthritis / Q000188:drug therapy; D011379:Prognosis; D011451:Prostaglandin-Endoperoxide Synthases; D012307:Risk Factors; D015983:Selection Bias; D013843:Thiazines / Q000009:adverse effects*; D013844:Thiazoles / Q000009:adverse effects*
D000894:Anti-Inflammatory Agents, Non-Steroidal; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors; D007527:Isoenzymes; D008565:Membrane Proteins; D013843:Thiazines; D013844:Thiazoles; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D011451:Prostaglandin-Endoperoxide Synthases; D000077239:Meloxicam