The Trial Bank initiative to promote trustworthy living evidence for medication safety (PROMISE) of children: design and pilot validation

BACKGROUND: While medications are essential for preventing and treating disease, they can also cause harm. Evidence synthesis has been widely adopted for evaluating harms, but traditional methods are resource-intensive and may constrain timely decision-making. This study aims to validate a Trial Bank approach towards rapid evidence synthesis. METHODS: A Trial Bank consisting of 13,650 RCTs of pharmaceutical or biopharmaceutical agents for children was established using artificial intelligence (AI) and humans, based on five databases (e.g., PubMed) up to February 14, 2023. The Trial Bank approach for evidence synthesis was validated in two ways: First, the percentage of trials within 1,996 Cochrane meta-analyses of drug safety in children that were also available in the Trial Bank was reported as the Trial Bank coverage (TBC). Second, the agreement of pooled effects from trials limited to those in the Trial Bank was compared to the full Cochrane meta-analyses in terms of their direction and statistical significance. RESULTS: Of 1,020 trials included in the Cochrane meta-analyses, there was an overall 80.2% TBC, with an average TBC of 85.7% per meta-analysis (n = 1,996). With regards to agreement of meta-analytical results, use of only the Trial Bank trials achieved an agreement of 93.0% (95% confidence interval [CI]: 90.8% to 94.8%) in the direction, 95.8% (95%CI: 94.0% to 97.2%) in significance, and 89.1% (95%CI: 94.0% to 97.2%) in both direction and significance to Cochrane meta-analytical results for meta-analyses that had 2 or more trials (n = 668). Sensitivity analysis by removing unpublished trials from Cochrane meta-analyses showed slightly higher agreement (e.g., 90.7% in both direction and significance). CONCLUSIONS: The Trial Bank approach demonstrated considerable coverage and agreement with Cochrane meta-analyses, suggesting it is a potentially feasible and efficient strategy for supporting living evidence synthesis of medication safety in children.