Proposed Core Set of Items for Measuring Disease Activity in Systemic Juvenile Idiopathic Arthritis.

OBJECTIVE: To date, there are no standardized disease activity tools for systemic juvenile idiopathic arthritis (sJIA). We developed a core set of disease activity measures for sJIA. METHODS: We conducted a validation study in patients with sJIA recruited from 3 Canadian institutions. Disease activity scores were based on questionnaires, clinical factors, and laboratory measures. The physician's global assessment was our criterion standard. We determined the strength of association of each item with the criterion standard. We then surveyed international experts to determine the top 10 items. Finally, we used the experts' responses to generate a proposed core set of disease activity measures. RESULTS: We enrolled 57 subjects - 26 with moderately or severely active disease, and 31 with mildly active or inactive disease. Items that most strongly correlated with the criterion standard were number of active joints (r = 0.79), parent's global assessment of disease activity (r = 0.53), erythrocyte sedimentation rate (ESR; r = 0.62), and C-reactive protein (CRP; r = 0.61). The response rate from international experts was 82% (154/187). Items with the most votes, in descending order, were number of active joints, number of days with fever in the preceding 2 weeks, patient's and parent's global assessments of disease activity, sJIA rash, ESR, CRP, and hemoglobin level. CONCLUSION: We propose a core set of items for measuring disease activity in sJIA. Future research should be aimed at further validation of this core set in the international context.

Using value-of-information methods when the disease is rare and the treatment is expensive--the example of hemophilia A.

BACKGROUND: Hemophilia A is a rare, sex-linked genetic disorder treated with intravenous administration of factor VIII (FVIII) to prevent bleeding; however, approaches vary across and within countries. Value-of-information (VOI) methods identify situations in which the cost-benefit evidence is sufficient to adopt one treatment strategy over another; when the evidence is insufficient, VOI methods provide the optimal sample size for additional research. OBJECTIVE: The objective of the study was to use VOI methods in a cost-benefit decision context to evaluate the current evidence in support of using (1) alternate day prophylaxis (AP), (2) tailored prophylaxis (TP) or (3) on-demand treatment (OD) with FVIII to prevent arthropathy in children with severe hemophilia A. METHODS: To apply VOI methods, several parameters such as incidence, time horizon for the decision, costs, and threshold values to avoid MRI-detected joint damage or arthropathy were defined. Two baseline threshold values of willingness to pay for avoiding arthropathy--$200,000 and $400,000--were selected for comparing the treatment strategies. RESULTS: For threshold values < $200,000, OD had a higher expected net benefit than either prophylaxis strategy, and the evidence was sufficient for its adoption. For threshold values > $400,000 prophylaxis strategies had higher expected net benefit; however, a new trial with 38 patients per arm was needed to compare AP and TP, yielding an expected net gain of over $17 million. In sensitivity analyses, the results were robust to assumptions regarding discount rate, trial fixed and variable costs, enrollment fraction, and the time horizon. CONCLUSIONS: In rare diseases, evidence is often scarce and insufficient for decision making. In considering the funding of new research and patient reimbursement in rare diseases, VOI methodology may provide more relevant determinations of the value and costs of additional research, compared to standard frequentist methods.

Revised versions of the Childhood Health Assessment Questionnaire (CHAQ) are more sensitive and suffer less from a ceiling effect.

OBJECTIVE: To determine the relative discriminant validity of 3 new versions of the Childhood Health Assessment Questionnaire (CHAQ) and to determine the relative concordance between children and their parents. METHODS: The parents of 48 children with musculoskeletal disability and 101 nondisabled controls were given the CHAQ and the 3 revised versions in random order. Children older than 5 years also completed the questionnaires. RESULTS: All 3 new versions of the CHAQ were more sensitive at differentiating patients from controls (relative efficiency 1.35-1.65); the versions with 8 added items were even more sensitive (relative efficiency 1.79-2.32). The new versions of the CHAQ suffered less from a ceiling effect and were more normally distributed. Concordance between children and parents was moderate to high for all versions. CONCLUSION: Researchers and clinicians should consider using a revision of the CHAQ. By being more sensitive at differentiating patients, the revised versions of the CHAQ will allow fewer subjects to be studied and will be more able to detect differences between patients in the clinic.