Expert Recommendations to Standardise Transcriptomic Analysis in Inflammatory Bowel Disease Clinical Trials

Abstract Background and aims Substantial methodological and reporting heterogeneity confounds interpretation and generalisability of transcriptomic data for inflammatory bowel disease (IBD) studies. We aimed to develop recommendations to standardise transcriptomic research in clinical trials. Methods A 2-part study was undertaken. A systematic review identified reports of transcriptomic analyses utilising samples from IBD clinical trials. Studies that used global RNA assay platforms were included. Data regarding study design, methodological approaches, and reporting of transcriptomic research were extracted. The systematic review results informed a modified Research and Development/University of California Los Angeles appropriateness methodology process, and development of survey statements focused on topics with substantial methodological heterogeneity. A panel of 16 IBD translational researchers and gastroenterologists rated the appropriateness of survey statements in 2 rounds. Results The systematic review identified 37 reports that included transcriptomic analyses of samples from IBD patients. The appropriateness of 416 statements were rated by 15 panellists in the first survey. The final survey included 305 statements, of which 14 panellists rated 75% appropriate, 1% inappropriate, and 24% uncertain. The panel determined that transcriptomic analysis for multiple research objectives was appropriate at most phases of clinical development in patients with active disease. Recommendations regarding study sample size; biopsy number, location, preservation, and storage; and data analysis and reporting were also generated. Conclusion Persistence of existing methodologic heterogeneity may continue to limit the value of transcriptomic research in IBD. This study provides expert recommendations to address and overcome these discrepancies and foster the inclusion of this research in clinical development.