From: Endoscopic ulcers as a surrogate marker of NSAID-induced mucosal damage
Hill criterion | Supportive evidence |
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Strength of association | There is a strong association between use of aspirin or NSAIDs and the development of both endoscopic ulcers and clinical bleeding events. Protective strategies have a large effect in preventing both events |
Consistency | There is a consistent effect across a range of different risk factors and interventions |
Specificity | Exposure to aspirin or NSAIDs causes a spectrum of gastrointestinal harm, but these are found without exposure. The link between aspirin and NSAIDs is specific only because of the elevation of the incidence rates |
Temporal relationship | Exposure to aspirin or NSAIDs precedes harm |
Biological gradient | There is a consistent dose response with aspirin and NSAIDs, with higher doses and longer use increasing the incidence rates of the harms |
Plausibility | There is a biological underpinning for upper gastrointestinal harm with aspirin and NSAIDs |
Coherence | The consistent effect of aspirin or NSAIDs on a broad spectrum of upper gastrointestinal harms, from symptoms, to endoscopic findings, to serious bleeding events, is evidence of coherence |
Experiment | A broad range of preventative therapies (misoprostol, histamine antagonists, proton pump inhibitors, coxibs) with different mechanisms of action all demonstrate significant reduction of harm with aspirin or NSAIDs |
Analogy | Detection of ulcers endoscopically in circumstances where aspirin or NSAIDs are not causative (for example where there may be infection with Helicobacter pylori) would be regarded as a marker of high risk for developing more serious ulcer disease with bleeding |