A Systematic Review for the Development of a Core Outcome Set for Ulcerative Colitis Clinical Trials.

BACKGROUND AND AIMS:

Advances in drug development for ulcerative colitis (UC) have been paralleled by innovations in trial design. Development of a core outcome set (COS) to standardize outcome definitions and reporting in clinical trials is desirable. We aim to systematically review the efficacy and safety outcomes reported in UC placebo-controlled RCTs.

METHODS:

We searched MEDLINE, EMBASE, and the Cochrane Library from inception through March 1, 2017 for placebo-controlled RCTs in adult patients with UC treated with aminosalicylates, immunosuppressants, corticosteroids, biologics, and oral small molecules. Efficacy and safety outcomes, definitions, and measurement tools were extracted and stratified by decade of publication.

RESULTS:

Eighty-three RCTs (68 induction, 15 maintenance) were included, enrolling 17,737 patients. Clinical or composite-clinical efficacy outcomes were reported in all trials; the Ulcerative Colitis Disease Activity Index (UCDAI) and the Mayo Clinic Score (MCS) were commonly used tools for assessing clinical response/remission. Remarkably, substantial variability in the definition of clinical or composite-clinical endpoints was observed with over 50 definitions of response or remission utilized. Endoscopic, histologic, and fecal/serum biomarker outcomes were reported in 83.1% (69/83), 24.1% (20/83), and 24.1% (20/83) of RCTs, respectively. A greater proportion of trials published after 2007 reported objective outcomes (96.5% endoscopic, 26.3% histologic, and 36.8% biomarker outcomes), but no standardized definitions of histologic or biomarker endpoints exists. Patient-reported efficacy and quality of life outcomes were described in 25 RCTs (30.1%) and safety outcomes were reported in 77 RCTs (92.8%).

CONCLUSIONS:

Despite recent advances in clinical trials methodology, important heterogeneity in reporting and variability in endpoint definitions still remains. A need exists to develop and validate a COS for UC clinical trials.