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

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.

How to decrease pharmaceuticals in the environment? A review

“…As highlighted, it is possible to work before the pharmaceutical life cycle starts-by increasing the health status/ wellness of humans (working in the downstream of health) and the quality of the environment (here, also combating climate change should be added). The actions preventing the diseases, such as healthy lifestyle and early diagnosis, have measurable benefits for society and lower the cost of healthcare (Chung et al 2020;de Boer et al 2020;Laroche et al 2020). The cost of actions is hard to determine, as well as the environmental profits, but generally, working in the downstream of the life cycle is connected with higher costs.…”

Exome first approach to reduce diagnostic costs and time – retrospective analysis of 111 individuals with rare neurodevelopmental disorders

“…Soden et al provide the mean costs of prior negative testing in non-acute individuals (inflated and currency converted value: 17,785.18€). Chung et al 43 , Monroe et al 42 and Vrijenhoek et al 22 calculated the cost savings per individual resulting from avoidable medical examinations due to early ES implementation (inflated and currency converted values: 110.63€; 3,277.66€ and 5,090.39€). In some of these publications the costs of potentially unnecessary diagnostics even exceeded costs for ES.…”

Rare genetic mutation triggering acute liver failure in a toddler requiring a liver transplant

“…Rapid WES can often provide results within 2 weeks and therefore may impact clinical decision‐making for a patient hospitalized with ALF 23 . Chung et al 24 reported that the median turnaround for rapid WES was 11 days and changed clinical management in 88% of patients with suspected monogenic disorders. In our patient, the results of rapid WES were reported within 5 days, which allowed us to quickly make the diagnosis of APS‐1.…”