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Preliminary definition of improvement in juvenile arthritis
E H Giannini1, N Ruperto, A Ravelli
1Children's Hospital Medical Center, Cincinnati, Ohio 45229-3039, USA.
Insights
Researchers defined improvement in juvenile arthritis (JA) using a core set of outcome variables. This standardized definition will aid clinical trials and treatment decisions for children with JA.
Area of Science:
- Pediatric Rheumatology
- Clinical Trial Methodology
- Outcome Measurement
Background:
- Juvenile arthritis (JA) assessment requires standardized outcome variables.
- A consistent definition of improvement is crucial for evaluating treatment efficacy in JA clinical trials.
Purpose of the Study:
- To establish a core set of outcome variables for JA assessment.
- To develop and validate a definition of clinical improvement for JA.
- To promote a uniform efficacy measure for JA clinical trials.
Main Methods:
- A core set of 6 outcome variables was identified (physician global assessment, parent/patient well-being, functional ability, active joints, limited motion joints, ESR).
- 21 pediatric rheumatologists used consensus techniques to score 72 patient profiles.
- Statistical analysis (sensitivity, specificity) and discriminant validity testing were performed on potential improvement definitions.
Main Results:
- The top-scoring definition of improvement: at least 30% improvement in 3 of 6 core variables, with no more than 1 variable worsening by >30%.
- This definition demonstrated convergent validity with established criteria.
- The proposed definition aims for high sensitivity and specificity in identifying true improvement.
Conclusions:
- A standardized definition of improvement for JA has been proposed.
- This definition will standardize JA clinical trial conduct and reporting.
- It will assist clinicians in determining adequate treatment response in children with JA.
Objective:
To identify a core set of outcome variables for the assessment of children with juvenile arthritis (JA), to use the core set to develop a definition of improvement to determine whether individual patients demonstrate clinically important improvement, and to promote this definition as a single efficacy measure in JA clinical trials.
Methods:
A core set of outcome variables was established using a combination of statistical and consensus formation techniques. Variables in the core set consisted of 1) physician global assessment of disease activity; 2) parent/patient assessment of overall well-being; 3) functional ability; 4) number of joints with active arthritis; 5) number of joints with limited range of motion; and 6) erythrocyte sedimentation rate. To establish a definition of improvement using this core set, 21 pediatric rheumatologists from 14 countries met, and, using consensus formation techniques, scored each of 72 patient profiles as improved or not improved. Using the physicians' consensus as the gold standard, the chi-square, sensitivity, and specificity were calculated for each of 240 possible definitions of improvement. Definitions with sensitivity or specificity of <80% were eliminated. The ability of the remaining definitions to discriminate between the effects of active agent and those of placebo, using actual trial data, was then observed. Each definition was also ranked for face validity, and the sum of the ranks was then multiplied by the kappa statistic.
Results:
The definition of improvement with the highest final score was as follows: at least 30% improvement from baseline in 3 of any 6 variables in the core set, with no more than 1 of the remaining variables worsening by >30%. The second highest scoring definition was closely related to the first; the third highest was similar to the Paulus criteria used in adult rheumatoid arthritis trials, except with different variables. This indicates convergent validity of the process used.
Conclusion:
We propose a definition of improvement for JA. Use of a uniform definition will help standardize the conduct and reporting of clinical trials, and should help practitioners decide if a child with JA has responded adequately to therapy. We are in the process of prospectively validating this definition and several others that scored highly.