Collaboration for Outcomes Research and Evaluation (CORE), Faculty of Pharmaceutical Sciences, University of British Columbia, Vancouver, British Columbia, Canada.
Department of Medical Genetics, Faculty of Medicine, University of British Columbia, Vancouver, British Columbia, Canada.
Genet Med. 2018 Sep;20(9):1013-1021. doi: 10.1038/gim.2017.226. Epub 2018 Jan 4.
This study aimed to generate benchmark estimates for the cost, diagnostic yield, and cost per positive diagnosis of diagnostic exome sequencing (ES) in heterogeneous pediatric patient populations and to illustrate how the design of an ES service can influence its cost and yield.
A literature review and Monte Carlo simulations were used to generate benchmark estimates for singleton and trio ES. A cost model for the Clinical Assessment of the Utility of Sequencing and Evaluation as a Service (CAUSES) study, which is testing a proposed delivery model for diagnostic ES in British Columbia, is used to illustrate the potential effects of changing the service design.
The benchmark diagnostic yield was 34.3% (95% confidence interval (CI): 23.2-46.5) for trio ES and 26.5% (95% CI: 12.9-42.9) for singleton ES. The benchmark cost of delivery was C$6,437 (95% CI: $5,305-$7,704) in 2016 Canadian dollars (US$4,859; 4,391€) for trio ES and C$2,576 (95% CI: $1,993-$3,270) (US$1,944; 1,757€) for singleton ES. Scenario models for CAUSES suggest that alternative service designs could reduce costs but might lead to a higher cost per diagnosis due to lower yields.
Broad conclusions about the cost-effectiveness of ES should be drawn with caution when relying on studies that use cost or yield assumptions that lie at the extremes of the benchmark ranges.
本研究旨在为异质性儿科患者群体中诊断外显子组测序（ES）的成本、诊断产量和每阳性诊断的成本生成基准估计值，并说明 ES 服务的设计如何影响其成本和产量。
文献回顾和蒙特卡罗模拟用于生成单体和三体型 ES 的基准估计值。使用不列颠哥伦比亚省正在测试的诊断 ES 拟议交付模型的临床评估效用测序和作为服务的评估（CAUSES）研究的成本模型来说明改变服务设计的潜在影响。
三体型 ES 的基准诊断产量为 34.3%（95%置信区间（CI）：23.2-46.5），单体 ES 为 26.5%（95%CI：12.9-42.9）。2016 年加拿大元（US$4,859；4,391€）的三体型 ES 交付基准成本为 6437 加元（95%CI：5305-7704），单体 ES 为 2576 加元（95%CI：1993-3270）（US$1,944；1,757€）。CAUSES 的情景模型表明，替代服务设计可以降低成本，但由于产量较低，每诊断的成本可能会更高。
在依赖成本或产量假设处于基准范围极端的研究来得出关于 ES 的成本效益的广泛结论时，应谨慎行事。
