Use of Patient-Reported Outcomes Measurement Information System Pediatric Measures as Clinical Trial Endpoints: Experience from a Multicenter Pragmatic Trial in Children with Crohn's Disease

Abstract

Objectives: To evaluate whether Patient-Reported Outcomes Measurement Information System (PROMIS) pediatric patient-reported outcome (PRO) measures can serve as valid endpoints in a clinical trial of a chronic pediatric illness.

Study design: We evaluated the responsiveness of PROMIS pediatric measures collected through the Clinical Outcomes of Methotrexate Binary Therapy in Practice (COMBINE) trial, a multicenter, randomized, double-blind, placebo-controlled, pragmatic clinical trial in pediatric patients with Crohn's disease (CD). We examined the relationships between changes in PROMIS pediatric measures and changes in disease activity by evaluating PRO score changes among patients who did and patients who did not experience improvement in disease activity.

Results: Participants included 266 children and adolescents with CD from a total of 35 institutions. Over the course of follow-up, participants showed improvement in most PRO domains, with the largest effect sizes observed for the clinically improved group. Patients who maintained steroid-free remission showed significantly lower PRO scores for the Pain Interference, Fatigue, and inflammatory bowel disease (IBD) Symptoms domains and higher scores for the Positive Affect domain.

Conclusions: This study demonstrates the responsiveness of the PROMIS pediatric measures of Fatigue and Pain Interference as study endpoints in a large, multicenter pragmatic trial in pediatric CD, extending a growing body of research supporting the use of PROMIS pediatric measures as reliable PRO endpoints for clinical trials.

Keywords: Crohn’s disease; PROMIS; child; inflammatory bowel disease; patient-reported outcomes.

Figure 1

Mean T-scores for 187 participants that remained in the study and completed PROs for at least one year post-baseline. Means were calculated by the order of PRO completion (1 = baseline, 2 = participants’ first follow-up PRO, etc.) up to participants’ fourth follow-up PRO. Higher scores indicate worse outcomes on Pain Interference, Fatigue, and IBD symptoms and better outcomes on Positive Affect. Bars represent the standard error of the mean.