There is an increasing demand for supporting the adoption of rapid whole-genome sequencing (rWGS) by demonstrating its real-world value. We aimed to assess the cost-effectiveness of rWGS in critically ill pediatric patients with diseases of unknown cause. Data were collected prospectively of patients admitted to the Nicklaus Children’s Hospital’s intensive care units from March 2018 to September 2020, with rWGS (N = 65). Comparative data were collected in a matched retrospective cohort with standard diagnostic genetic testing. We determined total costs, diagnostic yield (DY), and incremental cost-effectiveness ratio (ICER) adjusted for selection bias and right censoring. Sensitivity analyses explored the robustness of ICER through bootstrapping. rWGS resulted in a diagnosis in 39.8% while standard testing in 13.5% (p = 0.026). rWGS resulted in a mean saving per person of $100,440 (SE = 26,497, p < 0.001) and a total of $6.53 M for 65 patients. rWGS in critically ill pediatric patients is cost-effective, cost-saving, shortens diagnostic odyssey, and triples the DY of traditional approaches.

人们越来越需要通过展示其现实价值来支持采用快速全基因组测序 (rWGS)。我们的目的是评估 rWGS 在患有不明原因疾病的危重儿科患者中的成本效益。前瞻性收集了 2018 年 3 月至 2020 年 9 月尼克劳斯儿童医院重症监护室收治的患者的数据，使用 rWGS ( N = 65）。通过标准诊断基因检测在匹配的回顾性队列中收集比较数据。我们确定了根据选择偏倚和右删失调整的总成本、诊断率 (DY) 和增量成本效益比 (ICER)。敏感性分析通过自举探索了 ICER 的稳健性。rWGS 导致 39.8% 的诊断，而标准测试为 13.5% ( p  = 0.026)。rWGS 使每人平均节省 100,440 美元（SE = 26,497，p  < 0.001），65 名患者共节省 653 万美元。危重儿科患者的 rWGS 具有成本效益、节省成本、缩短诊断过程，并且是传统方法的三倍 DY。