Objective
Develop response criteria for juvenile dermatomyositis (JDM).
Methods
We analyzed the performance of 312 definitions that used core set measures (CSM) from either the International Myositis Assessment and Clinical Studies Group (IMACS) or the Pediatric Rheumatology International Trials Organization (PRINTO) and were derived from natural history data and a conjoint-analysis survey. They were further validated in the PRINTO trial of prednisone alone compared to prednisone with methotrexate or cyclosporine and the Rituximab in Myositis trial. Experts considered 14 top-performing candidate criteria based on their performance characteristics and clinical face validity using nominal group technique at a consensus conference.
Results
Consensus was reached for a conjoint analysis–based continuous model with a Total Improvement Score of 0-100, using absolute percent change in CSM with thresholds for minimal (≥30 points), moderate (≥45), and major improvement (≥70). The same criteria were chosen for adult dermatomyositis/polymyositis with differing thresholds for improvement. The sensitivity and specificity were 89% and 91-98% for minimal, 92-94% and 94-99% for moderate, and 91-98% and 85-85% for major improvement, respectively, in JDM patient cohorts using the IMACS and PRINTO CSM. These criteria were validated in the PRINTO trial for differentiating between treatment arms for minimal and moderate improvement (P=0.009–0.057) and in the Rituximab trial for significantly differentiating the physician rating of improvement (P<0.006).
Conclusion
The response criteria for JDM was a conjoint analysis–based model using a continuous improvement score based on absolute percent change in CSM, with thresholds for minimal, moderate, and major improvement.
Objective. Using serial N-of-1 trials and subsequent analysis with Bayesian methods may allow study of therapies using small numbers of subjects. Our research questions were: (1) Can serial N-of-1 trials analyzed with Bayesian statistical techniques be used to estimate the population effect of a therapeutic intervention? (2) Compared to placebo, how likely is it that low-dose amitriptyline therapy in children aged 10-18 years with active polyarticular-course juvenile idiopathic arthritis (JIA) results in a significant improvement in pain? Methods. Six children (age 10.3-16.3 yrs, 4 girls) were enrolled. There were 3 pairs of randomized, double-blinded treatments (amitriptyline 25 mg or placebo) per participant. Each treatment lasted 2 weeks, with a 1 week washout. The primary outcome was pain, measured by 10 cm visual analog scale. Assessments were at the beginning and end of each treatment. A Bayesian statistical model was used to determine the treatment effect. Values < 0 indicated superiority of amitriptyline. Results. Bayesian techniques were used successfully to obtain estimates of population effect, despite the small number of participants. The mean treatment effect for pain was 0.67 (SD 0.89, 95% credible interval -0.99, 2.55). The probability that the treatment effect was < 0 was only 16%. Conclusion. These methods can be used successfully to estimate population effects when sample sizes are small. It is unlikely that amitriptyline reduced pain by a clinically significant amount in these children with polyarticular JIA. These methods may be particularly suited to pilot studies and the study of rare illnesses.
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