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Systematic Review and Meta-analysis: An Empirical Approach to Defining Treatment Response and Remission in Pediatric
Luis C Farhat1, Edoardo F Q Vattimo1, Divya Ramakrishnan2
1Faculdade de Medicina FMUSP, Universidade de São Paulo, Brazil.
Insights
This study established optimal cutoffs for the Children's Yale-Brown Obsessive-Compulsive Scale (CY-BOCS) to define treatment response and remission in pediatric obsessive-compulsive disorder (OCD). These new benchmarks improve the consistency of clinical trial results for pediatric OCD.
Area of Science:
- Child and Adolescent Psychiatry
- Clinical Psychology
- Psychometric Validation
Background:
- Lack of standardized definitions for treatment response and remission in pediatric obsessive-compulsive disorder (OCD) hinders cross-trial comparisons.
- The Children's Yale-Brown Obsessive-Compulsive Scale (CY-BOCS) is widely used but lacks empirically derived, universal cutoffs for these outcomes.
Purpose of the Study:
- To conduct a diagnostic test accuracy meta-analysis of the CY-BOCS in pediatric OCD.
- To evaluate the discriminative ability of the CY-BOCS for response and remission.
- To generate empirically derived optimal cutoffs for response and remission using the CY-BOCS.
Main Methods:
- Individual participant data meta-analysis of 21 randomized controlled trials (N=1,234) identified from a systematic review of four databases.
- Utilized Clinical Global Impressions Improvement and Severity scales scores (≤2) to define response and remission.
- Employed a two-stage, random-effects meta-analysis model, calculating Area Under the Curve (AUC) and Youden Index to assess discriminative ability and determine optimal cutoffs.
Main Results:
- The CY-BOCS demonstrated strong discriminative ability for response (AUC=0.89) and remission (AUC=0.92).
- Optimal cutoff for response: a ≥35% reduction from baseline (sensitivity=83.9%, specificity=81.7%).
- Optimal cutoff for remission: a posttreatment score ≤12 (sensitivity=82.0%, specificity=84.6%).
Conclusions:
- Empirically derived optimal cutoffs for the CY-BOCS have been identified for response and remission in pediatric OCD clinical trials.
- Standardized operational definitions using these CY-BOCS cutoffs will enhance the comparability and reliability of research findings in pediatric OCD treatment studies.
Objective:
A lack of universal definitions for response and remission in pediatric obsessive-compulsive disorder (OCD) has hampered the comparability of results across trials. To address this problem, we conducted an individual participant data diagnostic test accuracy meta-analysis to evaluate the discriminative ability of the Children's Yale-Brown Obsessive-Compulsive Scale (CY-BOCS) in determining response and remission. We also aimed to generate empirically derived cutoffs on the CY-BOCS for these outcomes.
Method:
A systematic review of PubMed, PsycINFO, Embase and CENTRAL identified 5,401 references; 42 randomized controlled clinical trials were considered eligible, and 21 provided data for inclusion (N = 1,234). Scores of ≤2 in the Clinical Global Impressions Improvement and Severity scales were chosen to define response and remission, respectively. A 2-stage, random-effects meta-analysis model was established. The area under the curve (AUC) and the Youden Index were computed to indicate the discriminative ability of the CY-BOCS and to guide for the optimal cutoff, respectively.
Results:
The CY-BOCS had sufficient discriminative ability to determine response (AUC = 0.89) and remission (AUC = 0.92). The optimal cutoff for response was a ≥35% reduction from baseline to posttreatment (sensitivity = 83.9, 95% CI = 83.7-84.1; specificity = 81.7, 95% CI = 81.5-81.9). The optimal cutoff for remission was a posttreatment raw score of ≤12 (sensitivity = 82.0, 95% CI = 81.8-82.2; specificity = 84.6, 95% CI = 84.4-84.8).
Conclusion:
Meta-analysis identified empirically optimal cutoffs on the CY-BOCS to determine response and remission in pediatric OCD randomized controlled clinical trials. Systematic adoption of standardized operational definitions for response and remission will improve comparability across trials for pediatric OCD.
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