November 3rd, 2025

Clinical Trial Design Strategies for IBS and IBD

Though the two disorders may present similar symptoms, significant differences require distinct approaches to clinical trial design.

Anne Barnett, senior project oversight director, GI IBS indication champion

Anne Saene, senior oversight director, GI IBD indication champion

For those who suffer from irritable bowel syndrome (IBS) or inflammatory bowel disease (IBD), the two ailments can appear to be very similar — both are gastrointestinal (GI) disorders that can greatly impair a person’s quality of life, and both are currently only manageable, not curable. The two even share many symptoms, including abdominal pain and cramping, bloating and gassiness, constipation, diarrhea, and urgent bowel movements. And they often share a big challenge: The need to maintain a daily diary of symptoms and behaviors in order to aid diagnosis and care. On top of that, many patients also have the difficult task of trying to consistently self-assess and record nebulous and ever-changing levels of pain.

Conversely, for the biotech, biopharma and other specialist companies working to create drugs and other treatments, IBS and IBD are two distinct disorders that mostly require different approaches to drug development and clinical study conduct. In fact, differences can be seen in the competitive landscape itself:

IBD is an intensely competitive landscape with multiple ongoing trials underway, including pediatric trials. (To accommodate this volume, many investigator sites have overlapping trials.) Combined with the abundance of IBD drugs on the market, high trial volume can have the effect of driving down patient interest — though typically such declines are less prevalent among the un- or under-insured.
Fewer IBS studies currently underway, and existing trials are generally more focused on probiotics than on developing new treatments.

IBS and IBD from the patient’s perspective

IBS and IBD are each a pervasive global health concern. Some estimates show that IBS affects 500–900 million people globally, while approximately 7 million individuals worldwide suffer from IBD. The two ailments are not mutually exclusive: The Cleveland Clinic reports that 30%–50% of people with IBD also have IBS at the same time. Furthermore, many people with IBS are not diagnosed at all, and these patients may never consult or be seen by a GI practitioner. Given all these circumstances, diagnosis of IBS and IBD can be a difficult matter.

	IBS	IBD
Classification	Syndrome (a group of symptoms) Subtypes based on stool patterns: IBS-C – IBS with constipation IBS-D – IBS with diarrhea IBS-M – IBS with mix symptoms IBS-U – Undefined IBS	Disease Two main conditions: Ulcerative Colitis (UC) Crohn’s Disease (CD)
Inflammatory	No, does not cause permanent damage to intestines	Yes, can cause destructive inflammation and permanent harm to intestines
Area of GI tract affected	IBS affects the stomach and intestines—the gastrointestinal tract—which is responsible for digestion and nutrient absorption.	UC: Affected area starts at the anal verge and involves different extents of the colon. It typically involves only the mucosa, or the inner lining of the bowel. CD: Affected region can be anywhere from the mouth to the anus and often involves the small bowel. It can involve all layers of the bowels and cause fistulae, abscesses.
Hospitalization / surgery	Rare	Common
Genetic	No	Yes
Prevalence	More common	Less common
Patient gender	Twice as common in women	Roughly equal
Diagnosis	Based on symptoms, elimination of other causes No signs during examination of colon exam of the colon Fecal calprotectin always within the reference range	Diagnosis is based on more objective criteria: UC is based on symptoms and endoscopy CD is based on symptoms, diagnostic imaging and endoscopy
Risk factors	No increased risk for colon cancer or IBD	Risk factor for colon cancer
Symptoms	Abdominal pain and cramping Bloating and gassiness Constipation Diarrhea Urgent bowel movements
Symptoms	Mucus in bowel movements Feeling of incomplete bowel movements Nausea	Anemia Rectal bleeding Weight loss Fatigue Joint pain Fever
Treatment	Fiber, anti-diarrheal medication Antinauseants Biologics Antibiotics	Anti-inflammatory agenda Immunosuppressive agents Steroids Biologics

IBS and IBD from the drug developer’s perspective

IBS and IBD clinical studies share few commonalities beyond the need for patient diversity and the burden of regulatory compliance.

	IBS	IBD
Study design challenges	Patient diversity Complex regulatory demands, which often result in: Protocols that are complicated by requirements that may include long washout periods for prohibited medications, dependence on patient-reported outcomes, and the need to keep moderately to severely ill patients on placebo for several weeks Higher costs Longer times to complete studies Higher burden on patients, including daily data collection (eDiaries), more frequent colonoscopies, and restricted/prohibited concomitant medications
Study design challenges	Symptom variability Subject eligibility through diary Pain severity can affect screen failure rate Primary endpoints rely on patient-reported outcome (OTC medications, stool consistency/frequency, complete bowel movement, pain, etc.) Patient needs to maintain consistent diet and lifestyle	Low recruitment rate (especially for CD) Competitive or overlapping trials High number of approved drugs on the market with a different mechanism of action, but not greater than a 50% response rate
Possible Endpoints	Adequate relief of symptoms (using IBS-AR questionnaire) Stool consistency – BSFS Stool frequency IBS Symptom Severity Scale (IBS-SSS) IBS Quality of Life (IBS-QOL) EQ-5D-3L SF-12V2 Pain catastrophizing scale Diary of Irritable Bowel Syndrome Symptoms (DIBSS) IBS – Global Symptom Score	Proportion of patients with symptomatic and endoscopic remissions Modified Mayo Score (UC) CD Endoscopic Index (CD) Assessment of abdominal pain and stool frequency Rectal bleeding remission Endoscopy results and patient-reported outcome measures Histopathologic outcomes or “histological improvement,” per the U.S. Food and Drug Administration (FDA) (UC)
Study Design	Double-blind, randomized, placebo-controlled trials Diagnostic: Use Rome III or IV Criteria Symptom variability Patient diaries record daily symptom and OTC medications Pre-treatment period used to ensure stability of IBS symptoms	Run-in phase Re-randomization phase following clinical remission assessments is usual although ‘Treat Through’ designs are also used Diagnostic criteria Measurement of disease activity (e.g., endoscopy, histopathology, biomarkers)

Understanding IBS and IBD studies

Effective study design is a key factor in the success of any clinical trial. For drug developers working on IBS and IBD therapeutics, study design is made more challenging because it is often difficult to engage patients who are non-responsive to the currently available medications and have yet to achieve long-term remission and mucosal healing. The PPD™ clinical research business of Thermo Fisher Scientific understands the complexities of these types of studies, with experience engaging a diverse pool of participants and navigating this competitive landscape. Based on our vast experience working across gastrointestinal therapeutics, our team delivers key insight into such challenges as:

Which regions, countries and sites can deliver optimal enrollment to support a study
What protocol elements can be simplified and/or decentralized to make studies more appealing to sites and potential participants
How to maximize collection of critical endpoint data, especially patient-reported outcomes
How to find and enroll suitable, consenting patients by means of endoscopy and EMR data, or innovative methods such as AI technology
How to meet goals for representative enrollment from diverse patient populations

Over the past five years, we have partnered with drug developers on 125 GI-related trials across more than 6,900 sites, engaging nearly 24,000 patients along the way. This includes successful FDA inspections and FDA and sNDA approvals of IBS and IBD drugs. Throughout these trials, we’ve delivered faster-than-average start-up times, from final protocol and first patient dosed to last patient, last visit.

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