PDF(Pubmed)
Abstract：
Objective: Next-generation sequencing (NGS) technology, changing the diagnostic approach, has become essential in clinical settings, and its adoption by public health laboratories is now the practice. Despite this, as technological innovations, its intake requires an evaluation of both the clinical utility and the economic investment, especially considering the rare disease scenario. This study evaluated the analytical validity and the budget impact of an NGS-Ion Torrent™ approach for the molecular germline diagnosis of two musculoskeletal rare diseases. Methods: Two cohorts of 200 and 199 patients with suspect or clinical diagnosis of multiple osteochondromas (MO) and osteogenesis imperfecta (OI) previously evaluated with a single-gene diagnostic protocol were re-analyzed using a targeted NGS assay. Analytical validity was assessed by comparing NGS and single-gene protocol. A budget impact analysis using real-world cost data-considering the healthcare perspective- was performed by applying activity-based costing (ABC). The cost considered consumables, personnel, and equipment. Additional costs not related to NGS activities were not considered. Sensitivity analysis was performed. Results: The NGS method showed a higher (for MO) and comparable (for OI) diagnostic sensitivity than the traditional techniques, apart from always reducing the time and costs of diagnosis. Overall, the cost saving per patient is € 765 for OI and € 74 for MO. Materials represented the highest cost driver of the NGS process. A time saving-proportional to the panel size-has been assessed in both cases. Conclusions: Our targeted NGS diagnostic approach decreases time to diagnosis and costs, appearing to be beneficial and recommended both for patients and from a healthcare perspective in routine diagnosis also considering very small gene panels and a low patient flow. The adequate analytical sensitivity always required the additional Sanger sequencing step of the low- and non-covered regions. A more accurate strategy evaluation is suggested in the case of ultra-rare/complex diseases, large gene-panel, or non-reference diagnostic centers.
摘要：
目的:下一代测序(NGS)技术,改变诊断方法，在临床环境中变得至关重要，公共卫生实验室采用它是现在的做法。尽管如此,作为技术创新，它的摄入需要对临床效用和经济投资进行评估，特别是考虑到罕见疾病的情况。这项研究评估了NGS-IonTorrent™方法对两种肌肉骨骼罕见疾病的分子种系诊断的分析有效性和预算影响。方法：使用靶向NGS测定法重新分析了先前使用单基因诊断方案评估的200和199例可疑或临床诊断为多发性骨软骨瘤（MO）和成骨不全症（OI）的两组患者。通过比较NGS和单基因方案来评估分析有效性。通过应用基于活动的成本计算（ABC），使用考虑医疗保健观点的现实世界成本数据进行预算影响分析。考虑消耗品的成本，人员,和设备。没有考虑与NGS活动无关的额外费用。进行敏感性分析。结果：与传统技术相比，NGS方法显示出更高的（对于MO）和可比的（对于OI）诊断灵敏度，除了总是减少诊断的时间和成本。总的来说,OI每位患者的成本节省为765欧元，MO为74欧元。材料是NGS过程中成本最高的驱动因素。在这两种情况下都评估了与面板尺寸成正比的时间节省。结论：我们有针对性的NGS诊断方法减少了诊断时间和成本，似乎是有益的，建议对患者和从医疗保健的角度来看，在常规诊断中也考虑到非常小的基因组研究和低患者流量。足够的分析灵敏度总是需要低和未覆盖区域的额外Sanger测序步骤。在超罕见/复杂疾病的情况下，建议进行更准确的策略评估，大基因组，或非参考诊断中心。
