Psychometric evaluation of a pediatric functional constipation symptom diary using randomized phase 3 clinical trial data

Patient-reported outcomes (PROs) are required to assess the efficacy of treatments for functional constipation (FC), which is one of the most common functional gastrointestinal disorders in children. A novel PRO, the Pediatric Functional Constipation Symptom Diary (PFCSD), was developed to assess 7 core symptoms of FC (stool frequency, stool consistency, incomplete evacuation, straining, abdominal pain, abdominal bloating, and fecal incontinence) in pediatric FC patients. Here, we describe the psychometric analyses of the PFCSD using data from a phase 3 clinical trial of linaclotide (LIN-MD-64; NCT04026113) in children with FC. This psychometric evaluation assessed the measurement properties (reliability, validity, responsiveness) and meaningful within-patient change thresholds for symptom scores derived from the PFCSD. Since spontaneous bowel movement (SBM) frequency and stool consistency (measured using the pediatric Bristol Stool Form Scale in the PFCSD) were key endpoints for the phase 3 clinical trial of linaclotide, scores from these 2 items were the primary focus of these psychometric analyses. Daily and weekly responses on the PFCSD were assessed across a 14-week period from 328 pediatric patients aged 6 to 17 years who met the modified Rome III criteria for child/adolescent FC. Test-retest reliability, construct validity, and responsiveness of SBM frequency and stool consistency scores on the PFCSD were supported by this psychometric evaluation. Using intraclass correlation coefficients (ICCs), PFCSD scores on items measuring SBM frequency (ICC = 0.91) and stool consistency (ICC = 0.56) were consistent across repeated administrations. Convergent and discriminant correlations underscored the validity of SBM frequency and stool consistency scores on the PFCSD. The meaningful change threshold for weekly SBM frequency was identified as a change from baseline of ≥ 2 SBMs. For stool consistency, the meaningful change threshold ranged between + 0.8 to + 1.7 on the pediatric Bristol Stool Form Scale. The PFCSD is a novel, fit-for-purpose PRO measure evaluating key symptoms experienced by patients with FC aged 6 to 17 years. These analyses support the reliability, validity, and responsiveness of SBM frequency rate and stool consistency scores on the PFCSD in this target population and provide further guidance for interpreting meaningful changes in these scores at the individual level.