Channelling of patients taking NSAIDs or cyclooxygenase-2-specific inhibitors and its effect on interpretation of outcomes

Abstract

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.

Channeling and prevalence of cardiovascular contraindications in users of cyclooxygenase 2 selective nonsteroidal antiinflammatory drugs

“…Our data on channeling of coxibs are in line with group differences in observational studies that compared GI or cardiovascular safety between coxibs and NSAIDs (13)(14)(15)(16)(17)(18). MacDonald et al (18) and Schneeweiss et al (21) demon- * Values are the number (percentage) unless otherwise indicated.…”

“…A UK study of GI outcomes demonstrated that coxibs are prescribed to patients with a greater disease severity, more comorbid conditions, and higher prevalence of GI risk factors (18). The concurrent existence of cardiovascular disease risk and GI disease risk was not described.…”

Do proton‐pump inhibitors confer additional gastrointestinal protection in patients given celecoxib?

“…First, differences may exist between patients prescribed celecoxib and those prescribed celecoxib plus PPI, NSNSAIDs, or NS-NSAIDs plus PPI on variables that were not available in the database, such as diet, obesity, and alcohol consumption. Patients with these conditions are expected to be channeled to the celecoxib plus PPI group as opposed to the celecoxib, NS-NSAIDs plus PPI, or NS-NSAID groups (23). Although our models adjusted for measurable GI risk factors, available statistical models are limited in their ability to fully adjust for channeling bias.…”

Sensory and vascular changes in a rat monoarthritis model: prophylactic and therapeutic effects of meloxicam

“…COX-2 selective anti-inflammatory agents such as meloxicam have a better safety profile than conventional COX-1 and COX-2 nonselective anti-inflammatory agents. Meloxicam is a potent antiinflammatory agent that is commonly prescribed to treat arthritic conditions [29,30]. Moreover, inhibition of COX-2 has beneficial effects on nociceptive scores in animal models of inflammatory joint disease [31][32][33].…”