Due to a high placebo response rate in pharmacological trials in irritable bowel syndrome (IBS), researchers should incorporate a run-in period of at least 2 weeks and a dosing schedule of once or twice a day in future trials, according to a study published in The Lancet Gastroenterology & Hepatology.
Clinical trials for IBS have high placebo response rates. Therefore, researchers sought to determine the magnitude of these rates and their contributing factors. Investigators conducted a systematic review and meta-analysis of all randomized controlled trials that compared an active pharmacotherapeutic agent with placebo and had a dichotomous outcome of response to therapy in adults with IBS between April 1, 1959, and April 30, 2020.
They identified 6863 publications, with 70 articles describing 73 randomized controlled trials. The pooled placebo response rate was determined to be 27.3% using a global improvement end point, 34.4% using an abdominal pain end point, and 17.9% using a composite Food and Drug Administration end point responder definition, all with substantial heterogeneity between the trials.
Studies were significantly associated with an increased pooled placebo response rate if they were published before 2006, took place in Europe, had a parallel design, a run-in period of 2 weeks or less, a dosing schedule of three times a day or more, or a smaller sample size of the control group.
“On the basis of our findings, we suggest future pharmacological trials in IBS should use a run-in period of at least 2 weeks (preferably without a placebo therapy pending further research on this topic) and a daily dose of one or two times a day to minimise the pooled placebo response rate,” concluded the authors.
Disclosure: Several study authors declared affiliations with the pharmaceutical industry. Please see the original reference for a full list of authors’ disclosures.
Bosman M, Elsenbruch S, Corsetti M, et al. The placebo response rate in pharmacological trials in patients with irritable bowel syndrome: a systematic review and meta-analysis. Lancet Gastroenterol Hepatol. Published online March 22, 2021. doi: 10.1016/S2468-1253(21)00023-6