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. 2020 Jul 24:1:100001.
doi: 10.1016/j.lanwpc.2020.100001. eCollection 2020 Aug.

Rapid whole-exome sequencing facilitates precision medicine in paediatric rare disease patients and reduces healthcare costs

Claudia C Y Chung  1 , Gordon K C Leung  1 , Christopher C Y Mak  1 , Jasmine L F Fung  1 , Mianne Lee  1 , Steven L C Pei  1 , Mullin H C Yu  1 , Vivian C C Hui  1 , Joshua C K Chan  2 , Jeffrey F T Chau  1 , Marcus C Y Chan  1 , Mandy H Y Tsang  1 , Wilfred H S Wong  1 , Joanna Y L Tung  3 , Kin Shing Lun  2 , Yiu Ki Ng  2 , Cheuk Wing Fung  3 , Mabel S C Wong  2 , Rosanna M S Wong  3 , Yu Lung Lau  1   2   3 , Godfrey C F Chan  1   2   3 , So Lun Lee  2 , Kit San Yeung  1 , Brian H Y Chung  1   2   3
Affiliations

Rapid whole-exome sequencing facilitates precision medicine in paediatric rare disease patients and reduces healthcare costs

Claudia C Y Chung et al. Lancet Reg Health West Pac. .

Abstract

Background: Rapid whole-exome sequencing (rWES) offers the potential for early diagnosis-predicated precision medicine. Previous evidence focused predominantly on infants from the intensive care unit (ICU). This study sought to examine the diagnostic and clinical utility, and the economic impact on clinical management of rWES in patients beyond infancy and ICU setting.

Methods: rWES was performed on a prospective cohort of patients with suspected monogenic disorder referred from territory-wide paediatric ICUs and non-ICUs in Hong Kong urging for rapid genetic diagnosis. All eligible families were invited. We aimed to achieve a rapid turnaround time (TAT) of 14 days. Clinical utility and costs associated with clinical management were assessed in diagnosed cases. Actual quantitative changes in healthcare utilisation were compared with a counterfactual diagnostic trajectory and/or with matched historical control whenever possible.

Findings: rWES were offered to 102 families and 32/102 (31%) patients received a molecular diagnosis, with a median TAT of 11 days. Clinical management changed in 28 of 32 diagnosed patients (88%), including but not limited to modifications in treatment, avoidance of surgeries, and informing decisions on redirection of care. Cost analysis was performed in eight patients. rWES was estimated to reduce hospital length of stay by 566 days and decrease healthcare costs by HKD$8,044,250 (GBP£796,460) for these eight patients. The net cost-savings after inclusion of rWES costs were estimated to be HKD$5,325,187 (GBP£527,246).

Interpretation: This study replicates the diagnostic capacity and rapid TAT of rWES in predominantly Chinese patients, and demonstrates diagnosis-predicated precision medicine and net healthcare savings. Findings were corroborated by evidence from multinational cohorts, combined as part of a meta-analysis. rWES merits consideration as a first-tier diagnostic tool for patients with urgent needs in the clinical setting.

Funding: Health and Medical Research Fund, HKU Seed Fund for Basic Research, The Society for the Relief of Disabled Children, and Edward and Yolanda Wong Fund.

Keywords: Children; Healthcare cost-savings; Paediatric; Precision medicine; Rapid whole-exome sequencing; Rare disease.

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Conflict of interest statement

The authors declare that they have no competing interests.

Figures

Fig 1
Fig. 1
Impact on clinical management in 32 diagnosed patients. D Diagnostic testing; L Lifestyle changes; M Medication; O Others; P Procedure; R Referral; S Surveillance *A detailed version with specific changes in clinical management is available in Supplementary Table 3
Fig 2
Fig. 2
Comparing this study with other published rWES and rWGS studies. aCGH array comparative genomic hybridization; CI confidence interval; CICU cardiovascular intensive care unit; Dx diagnosis; G/C genetics clinic; IP inpatient; N/A not available; NICU neonatal intensive care unit; OP outpatient; PICU paediatric intensive care unit; RCT randomised controlled trial; rWGS rapid whole-genome sequencing; rWES rapid whole-exome sequencing; TAT turnaround time; urWGS ultra-rapid whole-genome sequencing
See this image and copyright information in PMC

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