- Fecal Incontinence
|Are They Side Effects? Extra-intestinal Symptoms Reported During Clinical Trials of IBS May Be More Severe at Baseline
Clin Gastroenterol Hepatol. 2022 Mar 23;S1542-3565(22)00293-2.doi: 10.1016/j.cgh.2022.03.018. Online ahead of print.
1Department of Medicine, Division of Gastroenterology, Beth Israel Deaconess Medical Center, Boston, Massachusetts; Program in Placebo Studies, Beth Israel Deaconess Medical Center/Harvard Medical School, Boston, Massachusetts. Electronic address: firstname.lastname@example.org.
2Department of Medicine, Division of Gastroenterology, Beth Israel Deaconess Medical Center, Boston, Massachusetts.
3Program in Placebo Studies, Beth Israel Deaconess Medical Center/Harvard Medical School, Boston, Massachusetts.
4Program in Placebo Studies, Beth Israel Deaconess Medical Center/Harvard Medical School, Boston, Massachusetts; Department of Psychology, Endicott College, Beverly, Massachusetts.
Background & aims: Many of the reported adverse events in clinical trials of irritable bowel syndrome are extraintestinal symptoms, which typically are assessed by open-ended questions during the trial and not at baseline. This may lead to misattribution of some pre-existing symptoms as side effects to the treatment.
Methods: The current study analyzed data from a 6-week clinical trial of irritable bowel syndrome. Participants were randomized to receive double-blind peppermint oil, double-blind placebo, or treatment as usual. Extraintestinal symptoms were assessed at baseline and at the end of the study.
Results: This analysis included 173 participants (30 received double-blind peppermint oil, 72 received treatment as usual, and 71 received double-blind placebo). At baseline, each group reported approximately 5 extraintestinal symptoms per participant. The number of symptoms per participant decreased to an average of 3 by the end-of-study visit, and this change was statistically significant in all groups (P < .001 for each group). When evaluating individual extraintestinal symptoms, the majority of participants did not report new/worse symptoms. In fact, between the baseline assessment and the final assessment, the average symptom severity decreased significantly in all 3 groups (P < .001).
Conclusions: Our study suggests that participants with irritable bowel syndrome often experience extraintestinal symptoms at baseline and that these symptoms generally improve in severity over the course of a clinical trial, regardless of the treatment arm. Systematic assessment of extraintestinal symptoms at the beginning of a clinical trial is necessary to determine more definitively whether these symptoms may be considered an adverse event attributable to a study medication.