Pediatr. 2022 Mar;242:86-92.e3.doi: 10.1016/j.jpeds.2021.10.053. Epub 2021 Nov 3.

Talya L Miller ¹, Julia Schuchard ², Adam C Carle ³, Christopher B Forrest ², Michael D Kappelman ⁴, COMBINE Study Group

Collaborators

COMBINE Study Group: 

Jeremy Adler, Rana F Ammoury, Dorsey Bass, Julie Bass, Keith Benkov, Athos Bousvaros, Brendan Boyle, José M Cabrera, Richard Colletti, Jill M Dorsey, Dawn R Ebach, Ann M Firestine, Ajay Gulati, Edward J Hoffenberg, Traci W Jester, Jess L Kaplan, Subra Kugathasan, Mark E Kusek, Ian Leibowitz, Tiffany M Linville, Peter Margolis, Phillip Minar, Zarela Molle Rios, Jonathan Moses, Pablo J Palomo, Helen Pappa, Dinesh S Pashankar, Shehzad A Saeed, Charles M Samson, Kelly C Sandberg, Steven J Steiner, Jennifer Strople, Jillian S Sullivan, Jeanne Tung, Prateek Wali

Author information

¹Department of Pediatrics, University of North Carolina at Chapel Hill School of Medicine, Chapel Hill, NC. Electronic address: Talya.Lepow.Miller@gmail.com.

²Department of Pediatrics, Children's Hospital of Philadelphia, Philadelphia, PA.

³Department of Pediatrics, Cincinnati Children's Hospital Medical Center, University of Cincinnati College of Medicine, Cincinnati, OH; Department of Psychology, University of Cincinnati College of Arts and Sciences, Cincinnati, OH.

⁴Department of Pediatrics, University of North Carolina at Chapel Hill School of Medicine, Chapel Hill, NC.

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.