Parental awareness, attitudes and decision-making of off-label use in children: a systematic review and meta-analysis

To systematically evaluate parental awareness, acceptance, refusal rate and influencing factors of off-label use in children, aiming to provide evidence for optimising informed consent and physician-parent communication.

We searched PubMed, Web of Science, Elsevier ScienceDirect, CNKI, Wanfang and VIP from inception to March 2026 for observational, mixed-methods and qualitative studies on parental awareness, attitudes and decision-making about off-label use in children. A random-effects single-group rate meta-analysis pooled awareness and refusal rates; conditional acceptance rates were summarised narratively due to extreme heterogeneity in operational definitions; unconditional acceptance rates were reported as individual study estimates. Influencing factors and psychological experiences were synthesised thematically.

Seven studies were included. The pooled parental awareness rate was 20.2% (95% CI: 10.6% to 31.9%), conditional acceptance ranged from 20.6% to 85.1% due to inconsistent operational definitions, unconditional acceptance was reported in two studies with individual estimates of 18.2% and 22.7%, and refusal was 36.5% (95% CI: 14.6% to 61.8%). Influencing factors fell into three themes: child clinical characteristics, parental cognition and emotion, and physician communication and qualification.

Parental awareness of off-label use in children is low. Part of parents accept conditionally; unconditional acceptance is limited, and refusal rates are relatively high. These three themes interact throughout the decision-making process. Postdecision caregiving experiences may lead to long-term scepticism and influence future attitudes. In clinical practice, informed consent should shift from procedural notification to trust-centred communication. Prescription and drug supply processes should be optimised to reduce parental care burden.