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Early Sequencing in Infants With Suspected Mendelian Disorders May Save Money

NEW YORK (GenomeWeb) – Sequencing infants with suspected monogenic conditions early in the diagnostic endeavor might save money in the long run, according to a new analysis.

A team of Australian researchers followed up on a cohort of 80 infants — who had undergone whole-exome sequencing to try to diagnose what appeared to be Mendelian disorders — and their families. In a study appearing this week in Genetics in Medicine, Susan White from Murdoch Children's Research Institute in Melbourne and her colleagues found that changes in clinical management based on those results led to a savings of A$1,578 ($1,186) per quality-adjusted life year gained. However, when they factored in additional usage of the health system by parents and siblings, the researchers noted there was an additional cost per QALY gained.

White and her colleagues wrote that "[t]hese data strengthen the case for the early use of genomic testing in the diagnostic trajectory, and can guide laboratory policy on periodic WES data reanalysis."

In their previous study, also in Genetics in Medicine, White and her colleagues examined the diagnostic and clinical utility of singleton WES and reported that for their cohort of 80 infants, they were able to generate WES-based diagnoses for 46 infants.

For this new analysis, they delved into how receiving that genetic diagnosis or not affected not only the clinical management of the infants, but also cascade testing, as well as the cost or savings of these changes and follow-on testing. They followed the cohort for a median 473 days after result disclosure.

Of the undiagnosed infants, seven were found to not have a monogenic disorder. But for those still suspected to have such a condition, clinicians continued to investigate the source. Nine of the 29 infants underwent further diagnostic evaluation — such as with Sanger sequencing or next-generation sequencing panel tests — at a cost of A$15,585, though no additional diagnoses were made.

When WES data was re-analyzed at six-month intervals, additional diagnoses were made for four infants.

White and her colleagues modeled the cost of re-analysis for two scenarios — re-analysis every six months or re-analysis at 18 months — versus the standard of care, and found that re-analysis at 18 months was the most cost-effective approach with an incremental cost savings of A$1,058.

Sixteen of the infants who received a diagnosis had changes to their clinical management following their WES results. For instance, one infant was diagnosed with alternating hemiplegia of childhood, which, if not treated, was expected to lead to further episodes and hospital admissions that would cost about A$13,063 a year. But with a change in treatment at a cost of A$336 a year, no further episodes or hospital admissions occurred, which the researchers said led to a savings of A$12,727.

Overall, the researchers estimated that management changes following WES diagnoses led to a cost savings of A$1,577 per additional QALY over standard care.

Diagnoses in the infants also led to testing among their siblings and parents, adding to the cost, the researchers noted.

Additionally, 16 parent-couples also sought reproductive genetic services. The cost of pre-implantation genetic diagnosis use for the couples that opted for it came to A$29,804, while prenatal diagnosis services cost A$27,100.

After folding in testing and clinical management among the infants' relatives, the researchers reported an incremental cost of A$8,118 per QALY gained.

However, the researchers noted that the lifetime value of eight additional children to the families and Australian society is likely to be far higher than the cost of providing reproductive genetic services.

"As health systems worldwide consider the implementation of genomic sequencing in routine clinical practice, these results provide valuable evidence to guide funders and services in the cost-effective use of this technology," the researchers wrote.

White and her colleagues noted, however, that their study is limited by its small size and that longer-term outcomes also need to be collected.