Comparative Effectiveness of Tumor Necrosis Factor Agents and Disease-modifying Antirheumatic Therapy in Children with Enthesitis-related Arthritis: The First Year after Diagnosis.

OBJECTIVE: To characterize the effect of anti-tumor necrosis factor (TNF) therapy compared to conventional synthetic disease-modifying antirheumatic drugs (csDMARD) in children with enthesitis-related arthritis (ERA) over the first year after diagnosis. METHODS: We conducted a multicenter retrospective comparative effectiveness study of children diagnosed with ERA. We estimated the effect of anti-TNF therapy on clinical variables (active joint count, tender entheses count) and patient-reported pain and global assessment of disease activity over the first year after diagnosis using state-of-the-art comparative effectiveness analytic methods. RESULTS: During the study period, 217 patients newly diagnosed with ERA had a total of 965 clinic visits the first year after disease diagnosis. Children [median age 11.6 yrs, interquartile range 10-14] were treated with anti-TNF monotherapy (n = 33, 15.2%), csDMARD monotherapy (n = 73, 33.6%), or both (n = 52, 23.9%) in the first year after disease diagnosis. There was a statistically significant improvement in the primary outcome, active joint count, over time in children who received an anti-TNF drug versus those who did not (p = 0.03). Additionally, use of anti-TNF therapy versus no anti-TNF therapy was associated with less patient-reported pain (p < 0.01) and improved disease activity over time as assessed by the clinical Juvenile Arthritis Disease Activity Score (p < 0.01). The magnitude of estimated effect on clinical outcomes was uniformly greater, with the exception of tender entheses count, in children treated with an anti-TNF drug versus a csDMARD. CONCLUSION: During the first year after diagnosis, anti-TNF exposure was associated with benefits for several clinically meaningful outcomes in children with enthesitis-related arthritis.

Validation of Patient-Reported Outcomes Measurement Information System Short Forms for Use in Childhood-Onset Systemic Lupus Erythematosus.

OBJECTIVE: To validate the pediatric Patient-Reported Outcomes Measurement Information System short forms (PROMIS-SFs) in childhood-onset systemic lupus erythematosus (SLE) in a clinical setting. METHODS: At 3 study visits, childhood-onset SLE patients completed the PROMIS-SFs (anger, anxiety, depressive symptoms, fatigue, physical function-mobility, physical function-upper extremity, pain interference, and peer relationships) using the PROMIS assessment center, and health-related quality of life (HRQoL) legacy measures (Pediatric Quality of Life Inventory, Childhood Health Assessment Questionnaire, Simple Measure of Impact of Lupus Erythematosus in Youngsters [SMILEY], and visual analog scales [VAS] of pain and well-being). Physicians rated childhood-onset SLE activity on a VAS and completed the Systemic Lupus Erythematosus Disease Activity Index 2000. Using a global rating scale of change (GRC) between study visits, physicians rated change of childhood-onset SLE activity (GRC-MD1: better/same/worse) and change of patient overall health (GRC-MD2: better/same/worse). Questionnaire scores were compared in support of validity and responsiveness to change (external standards: GRC-MD1, GRC-MD2). RESULTS: In this population-based cohort (n = 100) with a mean age of 15.8 years (range 10-20 years), the PROMIS-SFs were completed in less than 5 minutes in a clinical setting. The PROMIS-SF scores correlated at least moderately (Pearson's r ≥ 0.5) with those of legacy HRQoL measures, except for the SMILEY. Measures of childhood-onset SLE activity did not correlate with the PROMIS-SFs. Responsiveness to change of the PROMIS-SFs was supported by path, mixed-model, and correlation analyses. CONCLUSION: To assess HRQoL in childhood-onset SLE, the PROMIS-SFs demonstrated feasibility, internal consistency, construct validity, and responsiveness to change in a clinical setting.

A PROMIS Measure of Neuropathic Pain Quality.

OBJECTIVES: Neuropathic pain (NP) is a consequence of many chronic conditions. This study aimed to develop an unidimensional NP scale with scores that represent levels of NP and distinguish between individuals with NP and non-NP conditions. METHODS: A candidate item pool of 42 pain quality descriptors was administered to participants with osteoarthritis, rheumatoid arthritis, diabetic neuropathy, and cancer chemotherapy-induced peripheral neuropathy. A subset of pain quality descriptors (items) that best distinguished between participants with and those without NP conditions were identified. Dimensionality of pain descriptors was evaluated in a development sample and cross-validated in a holdout sample. Item responses were calibrated using an item response theory model, and scores were generated on a T-score metric. NP scale scores were evaluated in terms of the reliability, validity, and ability to distinguish between participants with and without conditions typically associated with NP. RESULTS: Of the 42 initial items, 5 were identified for the Patient-Reported Outcome Measurement Information System (PROMIS) Neuropathic Pain Quality Scale. T scores exhibited good discriminatory ability on the basis of receiver-operator characteristic analysis. Score thresholds that optimize sensitivity and specificity were identified. Construct, criterion, and discriminant validity, and reliability of scale scores were supported. CONCLUSIONS: The five-item Patient-Reported Outcome Measurement Information System (PROMIS PQ-Neuro) Neuropathic Pain Quality Scale is a short and practical measure that can be used to identify patients more likely to have NP and to distinguish levels of NP. The data collected will support future research that targets other unidimensional pain quality domains (e.g., nociceptive pain).

Item response theory, computerized adaptive testing, and PROMIS: assessment of physical function.

OBJECTIVE: Patient-reported outcome (PRO) questionnaires record health information directly from research participants because observers may not accurately represent the patient perspective. Patient-reported Outcomes Measurement Information System (PROMIS) is a US National Institutes of Health cooperative group charged with bringing PRO to a new level of precision and standardization across diseases by item development and use of item response theory (IRT). METHODS: With IRT methods, improved items are calibrated on an underlying concept to form an item bank for a "domain" such as physical function (PF). The most informative items can be combined to construct efficient "instruments" such as 10-item or 20-item PF static forms. Each item is calibrated on the basis of the probability that a given person will respond at a given level, and the ability of the item to discriminate people from one another. Tailored forms may cover any desired level of the domain being measured. Computerized adaptive testing (CAT) selects the best items to sharpen the estimate of a person's functional ability, based on prior responses to earlier questions. PROMIS item banks have been improved with experience from several thousand items, and are calibrated on over 21,000 respondents. RESULTS: In areas tested to date, PROMIS PF instruments are superior or equal to Health Assessment Questionnaire and Medical Outcome Study Short Form-36 Survey legacy instruments in clarity, translatability, patient importance, reliability, and sensitivity to change. CONCLUSION: Precise measures, such as PROMIS, efficiently incorporate patient self-report of health into research, potentially reducing research cost by lowering sample size requirements. The advent of routine IRT applications has the potential to transform PRO measurement.

Understanding treatment decision making in juvenile idiopathic arthritis: a qualitative assessment.

BACKGROUND: The increase in therapeutic options for juvenile idiopathic arthritis (JIA) has added complexity to treatment decisions. Shared decision making has the potential to help providers and families work together to choose the best possible option for each patient from the array of choices. As part of a needs assessment, prior to design and implementation of shared decision making interventions, we conducted a qualitative assessment of clinicians' current approaches to treatment decision making in JIA. METHODS: Pediatric rheumatology clinicians were recruited from 2 academic children's hospitals affiliated with a quality improvement learning network, using purposive and snowball sampling. Semi-structured interviews elicited how clinicians with prescribing authority (n = 10) interact with families to make treatment decisions. Interviews were audio-recorded and transcribed verbatim. A multi-disciplinary research team used content analysis to analyze the interview data.To validate data from individual interviews and enrich our understanding, we presented the interview results to pediatric rheumatology clinicians attending a learning network meeting (n = 24 from 12 children's hospitals). We then asked the clinicians questions to further identify and discuss areas of variation in the decision-making processes. RESULTS: Clinicians described a decision-making process in which they, rather than the family or other care team members, consistently initiated treatment decisions. Initial treatment options presented to families generally reflected the clinician's preferred treatment approaches, which differed across clinicians. Clinicians used various methods to inform families about treatment options and tailor information according to perceptions of a family's information needs, level of comprehension or mood (e.g. anxiety). The attributes of medication presented to families fell into 4 categories: benefits, risks, logistics and family preferences. Clinicians typically included family members in the decision to initiate JIA treatment after limiting the options to fit the clinical situation and the clinician's own preferences. Family members' preferences were seen as more integral in the decision to stop treatment after symptom remission. CONCLUSIONS: Decision making about initial JIA treatment appears to be largely driven by clinician preferences. Family preferences are more likely to be considered for treatment discontinuation. Opportunities exist to develop, test, and implement tools to facilitate shared decision making in pediatric rheumatology.

PROMIS Pediatric Peer Relationships Scale: development of a peer relationships item bank as part of social health measurement.

OBJECTIVE: This study's objective was to develop a measure of social health using item response theory as part of the Patient Reported Outcomes Measurement Information System (PROMIS). METHODS: After candidate items were generated from review of prior literature, focus groups, expert input, and cognitive interviews, items were administered to youth aged 8-17 as part of the PROMIS pediatric large scale testing. Exploratory and confirmatory factor analyses were used to assess dimensionality and to identify instances of local dependence. Items that met the unidimensionality criteria were subsequently calibrated using Samejima's Graded Response Model. Differential item functioning was examined by gender and age. RESULTS: The sample included 3,048 youth who completed the questionnaire (51.8% female, 60% white, and 22.7% with chronic illness). The initial conceptualization of social function and sociability did not yield unidimensional item banks. Rather, factor analysis revealed dimensions contrasting peer relationships and adult relationships. The analysis also identified dimensions formed by responses to positively versus negatively worded items. The resulting 15-item bank measures quality of peer relationships and has strong psychometric characteristics as a full bank or an 8-item short form. CONCLUSIONS: The PROMIS pediatric peer relationships scale demonstrates good psychometric characteristics and addresses an important aspect of child health.