Analysis
The Pediatric PROMIS-25 measured six HRQoL domains (Mobility, Anxiety, Depressive Symptoms, Fatigue, Peer Relationships, Pain Interference) by asking four questions per domain using a five-point Likert scale (e.g.,never, almost never, sometimes, often, almost always ; or,with no trouble, with a little trouble, with some trouble, with a lot of trouble, not able to ). Additionally, a single-item PROMIS Pain Intensity item was measured on a scale of 0 to 10. All items have a 7-day recall period.
Within each domain, a raw score was calculated as the sum of the answers to the four question items. Raw scores were transposed to standardized domain T-scores using tables provided by the PROMIS scoring manual, with a mean of 50 and standard deviation of 10.31 The PROMIS standardized T-score is composed from a mixed calibration sample of United States children in good health and children with a wide range of chronic conditions.32 Higher PROMIS scores for Mobility and Peer Relationships reflect better functioning and relationships, with scores < 40 (1 standard deviation (SD) below the mean) considered fair to poor.33 Higher symptom scores reflect worse symptom experiences (Anxiety, Depressive Symptoms, Fatigue, Pain Interference), with scores > 55 (1 SD above the mean) indicating moderate to severe symptom burden.33
Differences between diagnosis, active treatment, and follow-up domain mean T-scores were compared to published minimally important difference (MID) estimates of 2-3 points, and also analyzed using an ANOVA test.34 For sensitivity analyses, parent proxy-reported surveys were removed, as it has been demonstrated that caregivers consistently overestimate symptoms and underestimate function relative to child self-reports.35
Cohort characteristics were summarized using simple descriptive statistics. Patients were followed from enrollment until death, LTFU, or administrative censoring on January 31, 2020. We conducted an exploratory analysis to compare outcomes among patients with outcomes for those with poor versus adequate HRQoL domain scores. Kaplan-Meier methods were used to estimate overall survival and risk factors for mortality were assessed using univariate Cox proportional-hazards regression analysis to estimate hazard ratios (HR) of quantitative predictor variables. Analyses were conducted using R 3.5.2 (New York, New York).