Paul James Fortun

Background: Information sheets for clinical research are becoming increasingly complex but the extent to which they are understood is uncertain. Aims: To assess, as our primary outcome, recall by healthy volunteers of key facts in a patient information sheet in a phase 3 clinical trial. As secondary outcomes, we examined whether there was a difference between medical student and non-medically trained volunteers. Design: Questionnaire to determine recall by healthy volunteers of informed consent information. Methods: Eighty-two healthy volunteers participating in a capsule endoscopy study were given a 13 page written information sheet and allowed to asked questions. After indicating they were ready to give consent they were asked to complete a 6-item questionnaire covering the identity and adverse effects of trial treatments and of the procedure, the duration of the trial and value of the inconvenience allowance. Results: All 82 healthy volunteers were questioned. Of the volunteers, 74 (90%) had university level education and 49 (60%) were clinical medical students. However, only 10 subjects (12%) could name the three trial drugs. The maximum number of risks remembered was 6 (n = 2) of 23. Only 14 (17%) could name three or more potential risks of the medication they might be exposed to, whilst 17 (20%) could identify none. Most subjects (77/82, 90%) identified capsule endoscopy as the trial procedure and impaction/obstruction as its main risk (52/82, 64%). All but one subject (98.8%) could recall the exact value of the inconvenience payment. Conclusion: A comprehensive information sheet resulted in limited recall of trial risks. Shorter information sheets with a test and feedback session should be trialled so that informed consent becomes valid informed consent.

The small intestine may be a more common site for nonsteroidal antiinflammatory drug toxicity than the gastroduodenal mucosa. Two-thirds of regular nonsteroidal antiinflammatory drug users develop subclinical small bowel enteropathy. This review highlights this emerging issue in patients requiring antiinflammatory drugs. Nonsteroidal antiinflammatory drug enteropathy is a stepwise process involving direct mucosal toxicity, mitochondrial damage, breakdown of intercellular integrity, enterohepatic recirculation and neutrophil activation by luminal contents including bacteria. Unlike upper gastrointestinal toxicity, cyclooxygenase-mediated mechanisms are probably less important. Newer imaging modalities such as capsule endoscopy studies demonstrate nonsteroidal antiinflammatory drug-induced small bowel erosions, but the clinical implications are unclear. Nonsteroidal antiinflammatory drug toxicity to the small intestine is common. Useful research tools have been developed to indirectly measure intestinal inflammation and permeability, but these are not generally available to the clinician, although enteroscopy and capsule endoscopy can be illuminating. Anaemia or hypoalbuminaemia are useful indications of nonsteroidal antiinflammatory drug enteropathy. Cessation of the drug would be the preferred option, alternatively there are experimental data to support the use of sulphasalazine and metronidazole. Animal models are unravelling new mechanisms for mucosal toxicity beyond the cyclooxygenase model, including mucosal oxidative injury and nitric oxide mediated pathways.

The small intestine is a more common site for nonsteroidal antiinflammatory drug (NSAID) toxicity than the well-recognized effects on the stomach and duodenum. Although NSAID strictures and perforation are rare, two thirds of regular NSAID users may be prone to small bowel enteropathy. This review highlights this emerging issue in patients requiring antiinflammatory drugs. NSAID enteropathy is a stepwise process involving direct mucosal toxicity, mitochondrial damage, breakdown of intercellular integrity, enterohepatic recirculation, and neutrophil activation by luminal contents, including bacteria. Unlike upper gastrointestinal toxicity, cyclooxygenase-mediated mechanisms are probably less important. Newer imaging modalities such as capsule endoscopy studies suggest that small bowel erosions may be common in nonselective NSAID users. Sulfasalazine and metronidazole may prove to be useful, therapeutic options for patients who cannot cease their NSAIDs. NSAID toxicity to the small intestine is common. Useful research tools have been developed to measure intestinal inflammation and permeability indirectly, but these are not generally available to the clinician, although enteroscopy and capsule endoscopy may be helpful. Anemia or hypoalbuminemia are useful clues to NSAID enteropathy. Cessation of the drug is ideal; otherwise, there is experimental data to support the use of sulfasalazine and metronidazole. Animal models are unraveling new mechanisms for mucosal toxicity beyond the yclooxygenase model.