Despite advances in methods of clinical trials for ulcerative colitis (UC), there is still a large amount of variation in endpoints, even in definitions of response and remission, reseachers found in a systematic review published in the May issue of Clinical Gastroenterology and Hepatology. The authors conclude that we need a core set of outcomes to standardize efficacy and safety reporting for trials of patients with UC.
Clinical trials of inflammatory bowel diseases have become larger and more sophisticated and treatment targets have changed, from symptom-based scoring assessments to objective measures of inflammation based on endoscopic appearance, biomarkers, and histologic factors. The Food and Drug Administration (FDA) requires inclusion of patient-reported outcomes (PROs) as clinical trial endpoints.
Christopher Ma et al performed a systematic review of efficacy and safety outcomes reported in trials of patients with UC.
Ma et al collected data from placebo-controlled randomized trials of adult patients with UC treated with aminosalicylates, immunosuppressants, corticosteroids, biologics, or oral small molecules, published through March 2017. They assessed information on efficacy and safety outcomes, definitions, and measurement tools, stratified by decade of publication.
In an analysis of 168 induction and and 15 maintenance trials, comprising 17,737 patients, the authors found that a clinical response or improvement was reported in 83.8% of the induction trials and 73.3% of the maintenance trials. A combination of clinical and endoscopic remission was used as the endpoint of 11 induction studies. Among maintenance trials, 5 trials reported clinical relapse or worsening as a study endpoint.
Fifty-five of 57 randomized controlled trials published after 2006 described endoscopic outcomes (see figure). Histologic outcomes were also increasingly reported since 2006 with heterogeneous outcome definitions.
However, more than 50 different definitions of response or remission were used in the studies.
Biomarker outcomes were used in 26.5% of induction and 13.3% of maintenance trials, with reductions in fecal calprotectin and C-reactive protein most commonly measured.
Most studies reporting PROs were published after 2006 (38.6%). Quality of life was frequently assessed using the inflammatory bowel disease questionnaire, with a positive response defined by a 16-point increase in score (or score ≥170). Other tools for assessing quality of life included the IBD patient-reported treatment impact survey, the 36-item short form survey, the EuroQoL survey, and rectal bleeding and stool frequency PROs.
Ma et al state that therapeutic efficacies and safety cannot be compared among treatment stateigies when such significant heterogeneity in outcome definitions exists—a core outcome set is needed. As PROs become an increasingly central component in assessing treatment response, definitions and units of meaningful change must be standardized.
In an editorial in the same issue, Siddharth Singh writes that Ma et al are at the forefront of IBD clinical trial design, and anticipate that validated multi-dimensional PROs, developed under FDA guidance, will be an integral component of efficacy measures in trials. This will allow better translation of trial findings into clinical practice.
A practice management: the road ahead article on PROs in the same issue, written by Erica R Cohen and Gil R Melmed, states that these measures are likely to affect treatment of gastrointestinal and systemic symptoms, overall and emotional quality of life, and coping behaviors.