Development and Validation of a Rapid Benefit-Risk Assessment Index for Pediatric Off-Label Drug Use.

OBJECTIVE

To develop and validate a rapid, evidence-based benefit-risk assessment index for off-label drug use in pediatrics, thereby promoting standardized clinical decision-making.

METHODS

Under the auspices of the Guangdong Pharmaceutical Association, a multidisciplinary expert panel from pediatrics, pharmacy, methodology, and ethics was convened. Systematic literature searches informed a preliminary index framework. Three Delphi rounds refined indicators. Weights were assigned using the analytic hierarchy process. Expert-based validation involved 20 hematology-oncology experts assessing 10 cases; intraclass correlation coefficient (ICC) and Spearman's correlations evaluated reliability and validity.

RESULTS

The index consists of 2 primary dimensions (benefits: 56 points; risks: 44 points), 10 third-level, and 40 fourth-level indicators, with five prerequisites (e.g., no alternatives, informed consent). The ICC was 0.77 (good reliability); Spearman's correlations were rs = 0.97 (benefits) and rs = 0.68 (risks) (both p < 0.05), indicating strong alignment with expert consensus. Junior experts showed lower correlations (benefits rs = 0.89; risks rs = 0.56) than seniors (benefits rs = 0.97; risks rs = 0.78), highlighting the system's role in standardizing assessments.

CONCLUSION

This quantitative index provides an evidence-based tool for pediatric off-label drug decisions, supporting clinicians, policymakers, and standardization efforts.