Entry criteria for drug trials of irritable bowel syndrome

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This review explores a broad range of patient characteristics that might be considered when selecting patients for inclusion into drug trials for irritable bowel syndrome (IBS). These characteristics have been chosen according to the author’s perspective and a review of the literature based on a Medline search encompassing references to IBS (clinical, pharmacologic, and drug trials) from 1966 to 1998. The focus is to improve patient selection, which until now has concentrated predominantly on physical symptoms. Irritable bowel symptoms involve both physical and psychological domains in an inseparable way, the interaction profoundly affecting the physical manifestations of the condition, the patient’s interpretation of these physical changes, the ability of the patient to cope with these symptoms, the extent to which the patient feels the need to seek treatment, and the response to different types of treatment. Selection criteria need to take both physical and psychological domains into account. When defining the disorder for purposes of patient selection, a simple definition of long-standing abdominal pain and bloating associated with alternating diarrhea and constipation (after the exclusion of organic disease) may still be the most practical. The Manning and Rome criteria have been reasonably well validated, especially when the constellation of symptoms is used as a unit; however, their applicability to men and the elderly is not as well validated and deserves further attention. Other patient characteristics that may be useful in the future in deciding suitability for a trial, or predicting response, include symptom pattern, length of symptom history, whether the condition was triggered by enteric infection, whether a patient is in primary, secondary, or tertiary care, psychological characteristics, a history of physical or sexual abuse, and possibly visceral sensitivity testing or autonomic dysfunction. Different studies may be required for primary care and tertiary care patients, who may differ in their psychological characteristics. Studies should also include patients across the demographic spectrum who are likely to require treatment for this condition, including adolescents and the elderly. The type of drug being tested will also influence patient selection, depending on whether it is fast or slow acting, and its predominant pharmacologic effects and side effects. This has particular relevance in relation to the presence of diarrhea or constipation, how prominent the symptom of pain is, and whether the drug has psychotropic or anxiolytic effects. Because of the recognition that IBS patients compose a heterogeneous population, precise characterization of patients, and targeted drug therapies are likely to lead to better therapeutic results. Further attention also needs to be paid to the type of drug under investigation, in relation to these different patient characteristics.