Irritable bowel syndrome (IBS) is the most common gastroenterology referral and is defined by abdominal pain associated with altered bowel habits. In the absence of objective biomarkers, patient perception of symptoms means everything. Evaluating IBS treatment response in practice relies on the physician to ask their patient if they feel better. A simple question, yet one that is greatly influenced by preconceived expectations of treatment outcomes, frequency of care received, and even side-effects of treatment, which can predispose a patient toward perceiving that a treatment is working. 1 Kaptchuk TJ Kelley JM Conboy LA et al. Components of placebo effect: randomised controlled trial in patients with irritable bowel syndrome. BMJ. 2008; 336: 999-1003 Crossref PubMed Scopus (814) Google Scholar , 2 Ballou S Beath A Kaptchuk TJ et al. Factors associated with response to placebo in patients with irritable bowel syndrome and constipation. Clin Gastroenterol Hepatol. 2018; 16: 1738-1744.e1 Summary Full Text Full Text PDF PubMed Scopus (18) Google Scholar , 3 Shah E Triantafyllou K Hana AA Pimentel M Adverse events appear to unblind clinical trials in irritable bowel syndrome. Neurogastroenterol Motil. 2014; 26: 482-488 Crossref PubMed Scopus (18) Google Scholar As recently as 10 years ago, the basic question of whether a patient achieved adequate or global relief of symptoms was the most common (and most sensible) endpoint for clinical trials. Yet this endpoint yielded placebo response rates reaching around 40%. Taken even further, active placebo (with informed consent) has even shown promise as an IBS treatment. 4 Kaptchuk TJ Friedlander E Kelley JM et al. Placebos without deception: a randomized controlled trial in irritable bowel syndrome. PLoS One. 2010; 5e15591 Crossref PubMed Scopus (532) Google Scholar These realities allude to the challenges in evaluating investigational IBS treatments in randomised, placebo-controlled trials. The placebo response rate in pharmacological trials in patients with irritable bowel syndrome: a systematic review and meta-analysisMore than a quarter of patients with irritable bowel syndrome had a placebo response in terms of global improvement, with multiple associated moderators. We recommend future trials apply a run-in period of at least 2 weeks and dose once or twice a day to minimise the placebo response rate. Full-Text PDF