An international consensus on the design of clinical trials for advanced combination treatment (ACT) in inflammatory...

Area of Science:

• Gastroenterology
• Clinical Trial Design
• Precision Medicine

Background:

• Advanced Combination Treatment (ACT) involves using two advanced therapies (biologics or small molecules) for inflammatory bowel disease (IBD).
• Current clinical trial designs for ACT in IBD lack standardized guidance, creating uncertainties in eligibility, pharmacotherapy, safety, and trial configurations.
• Expert recommendations are needed to address these gaps and facilitate efficient ACT clinical trials.

Purpose of the Study:

• To formulate expert recommendations for designing clinical trials of Advanced Combination Treatment (ACT) in patients with inflammatory bowel disease (IBD).
• To address key uncertainties in trial design, including eligibility criteria, pharmacotherapy, safety, and standardized configurations for induction and maintenance phases.
• To provide a framework for conducting efficient and informative clinical trials of ACT in IBD.

Main Methods:

• A systematic literature search was conducted in June 2023.
• The Modified RAND/University of California, Los Angeles Appropriateness Methodology (RAM) was used to evaluate 287 statements on ACT clinical trial design in IBD.
• A multidisciplinary expert panel rated statement appropriateness, followed by consensus meetings to categorize statements as appropriate, uncertain, or inappropriate.

Main Results:

• ACT should combine drugs with distinct mechanisms of action.
• Appropriate eligibility criteria include prior treatment failure and high risk for complications; short-term high-risk regimens are acceptable for induction.
• Trial designs should compare ACT to monotherapy, allow longitudinal evaluation, and use co-primary endpoints of clinical remission and endoscopic response, with safety outcomes including adverse events and infections. Precision medicine approaches are essential.

Conclusions:

• Standardized design elements for eligibility, pharmacotherapy, safety, and trial configurations are essential for efficient ACT clinical trials in IBD.
• Implementing these recommendations will improve the quality and comparability of clinical trial data for ACT in IBD.
• Expert consensus provides a foundation for future research and clinical practice involving ACT for IBD management.