Clin Nutr. 2024 May;43(5):1079-1086. doi: 10.1016/j.clnu.2024.03.017.Epub 2024 Mar 27.

Thomas Edward Conley ¹, Miles Parkes ², Stephen Moss ², Chris Probert ³

Author information

¹University of Liverpool Institute of Integrative Biology, Liverpool, UK; Liverpool University Hospitals NHS Foundation Trust, Department of Gastroenterology, Liverpool, UK. Electronic address: Tconley@liverpool.ac.uk.

²University of Cambridge Department of Medicine, Gastroenterology and Hepatology, Cambridge, Cambridgeshire, UK; Cambridge University Hospitals NHS Foundation Trust, Department of Gastroenterology, Cambridge, UK.

³University of Liverpool Institute of Integrative Biology, Liverpool, UK; Liverpool University Hospitals NHS Foundation Trust, Department of Gastroenterology, Liverpool, UK.

Abstract

Background & aims: The low-FODMAP diet (LFD) has become almost synonymous with IBS care, yet the challenges associated with this rigorous therapeutic approach are often underacknowledged. Despite positive outcomes in RCTs, comparator groups frequently exhibit substantial response rates, raising questions about the definition of 'response'. Whilst the assessment of response in drug trials has evolved to utilize the more stringent FDA/EMA primary clinical endpoints, trials of the LFD have not yet followed. The aim of this article is to opine whether the current approach to the measurement of clinical response to the LFD in clinical trials should be reconsidered.

Methods: A comprehensive literature review of LFD clinical trials from the past decade was conducted, focusing on recorded response metrics for primary clinical endpoints.

Results: While response definitions vary, the 50-point IBS-SSS delta emerged as the predominant metric. Notably, no trials to date have adopted the more stringent primary clinical endpoints used in drug trials. Other response measures included binary response metrics (such as 'adequate clinical response'), changes in visual analogue scales or stool form/output, reductions in abdominal pain, as well as changes the magnitude of the IBS-SSS delta. Whether these metrics correspond to a clinically meaningful improvement for the patient is less clear, and as such aligning patient-clinician expectations can be challenging.

Conclusions: A paradigm shift in the conceptualization of 'response' coupled with an emphasis on harder clinical endpoints in the context of clinical trials may serve to better justify the trade-off between symptom-improvement and the inherent challenges associated with this burdensome therapeutic approach.