Description
This guidance is intended to assist the pharmaceutical industry and investigators who are developing drugs for the treatment of irritable bowel syndrome (IBS). IBS diagnosis and assessment of clinical status depend mainly on an evaluation of IBS signs and symptoms that are known to the patient. Capturing all of the clinically important signs and symptoms associated with IBS in a reliable measure of treatment benefit can be challenging. The guidance for industry Patient-Reported Outcome Measures: Use in Medical Product Development to Support Labeling Claims (PRO guidance)3 defines the term treatment benefit as “[t]he effect of treatment on how a patient survives, feels, or functions.”
Key Topics
Terms and concepts identified from this document
Scope & Applicability
Product Classes
4Licensed under section 351 of the Public Health Service Act.
Defined in section 201(g) of the FD&C Act; Articles intended for use in diagnosis, cure, mitigation, treatment, or prevention of disease; Product classification based on chemical action or specific intended uses like altering pH
Irritable Bowel Syndrome with Constipation patient population
Irritable Bowel Syndrome with Diarrhea patient population
Stakeholders
3Assist sponsors in the nonclinical evaluation
Guidance for Sponsors, Investigators, and Institutional Review Boards
Entity responsible for submitting applications under section 524B
Regulatory Context
Regulatory Activities
4Process for the future development of IBS PRO instruments.
Regulatory pathway for IBS and Functional Dyspepsia treatments
Claims supported by data collection from appropriate PRO instruments.
Conclusion that a DDT can be relied upon in regulatory decision-making
Document Types
4Patient-reported outcome instrument used for primary endpoints in phase 3 trials
A 5-Point Likert scale used to rate relief of symptoms in clinical trials.
include the overall strategy for handling different intercurrent events... in the statistical analysis plan
providing reminders to trial subjects to complete PRO instruments
Attributes
4Categorization based on pain intensity and stool frequency/consistency
Categorization based on daily pain and stool consistency scores
Measured by the number of complete spontaneous bowel movements (CSBMs) per week.
Recommended primary endpoint for IBS-D trials.
Technical Details
Substances
3Drug used in IBS-D clinical trials with adequate relief as a primary endpoint.; 5-HT3 receptor antagonist mentioned in references; Evaluated for safety and efficacy in women with severe diarrhea-predominant IBS
Drug used in IBS-C clinical trials with satisfactory relief as a primary endpoint.; 5-HT4 receptor partial agonist evaluated in multiple clinical trials for IBS
Drug used in IBS-C clinical trials using a modified version of the SGA.; Improves symptom relief rates in adults with IBS
Testing Methods
8The primary tool for defining treatment effect in IBS clinical trials.
Tool for pain assessment in clinical trials
Guide to intestinal transit time
Method to assess the impact of treatment on IBS-related symptoms
A single-item patient-reported rating of change used in past trials.
Recommended scale (0 to 10) for evaluating abdominal pain intensity.
Recommended study design for IBS treatments.
Response options for patient rating of change
Clinical Concepts
10The primary disease state addressed by the guidance.; Primary disease state addressed by the clinical evaluations
Pain that persists longer than 3 months.; Drug development programs for the treatment of chronic pain have historically been challenging; target condition for the analgesics discussed; Target condition for the analgesics discussed
Specific patient population for Alosetron studies
A specific subtype of IBS (IBS-D) to which the guidance applies.
A specific subtype of IBS (IBS-C) to which the guidance applies.; Specific patient population for Tegaserod and Lubiprostone studies
One of the five core signs and symptoms
Irritable Bowel Syndrome with diarrhea subtype.
Irritable Bowel Syndrome with constipation subtype.
A major IBS sign and symptom recommended as a component of the primary endpoint.
Primary endpoint for IBS clinical trials
Standards & References
External Standards
5Criteria and outcomes defined by the Rome Foundation for functional bowel disorders
Core outcome measures and domains for chronic pain clinical trials
A pictorial and verbal description of stool consistency and form used in IBS trials.
Diagnostic criteria used to enroll patients in prospective IBS clinical trials.
Bristol Stool Scale used to measure stool consistency
Specifications
4Main measures used to assess efficacy in CIPN trials.
Proportion of patients who do not have any heavy drinking days
Complete Spontaneous Bowel Movement used as a measure for stool frequency
Responder definition threshold for abdominal pain intensity
Related CFR Sections (1)
- 21CFR314.126§ 314.126 Adequate and well-controlled studies.
(a) The purpose of conducting clinical investigations of a drug is to distinguish the effect of a drug from other influences, such as spontaneous change in the course of the disease, placebo effect, or biased observation. The characteristics described in paragraph (b) of this section have been develRead full regulation →
Related MFDS Guidelines
Korean regulatory guidelines covering similar topics