Working with the East Anglian Medical Genetics Service Laboratory, we are investigating whether a single assay using a clinical exome approach - which targets 4,813 known clinically relevant genes - could offer the best attributes of both the targeted gene panel and whole exome or genome approaches for testing a portfolio of disorders. Our economic evaluation, based on mapping and costing the potential genetic testing pathways from the viewpoint of the laboratory, suggests it could.

Mapping the testing pathways

Through discussion with the East Anglian Medical Genetics Laboratory we were able to identify, define and map the testing pathways, and determine the procedures required to complete each testing pathway (GEMINI pathway pictured below, click to expand).

Calculating costs

A total cost for each patient was calculated depending on the pathway taken and genetic tests conducted. The main health outcome of interest is the number of genetic diagnoses defined as a patient who has a variant detected by a genetic test that is judged to confirm the clinical diagnosis.

An initial cost-analysis of 196 patients with known mutations in 74 different genes, previously confirmed by Sanger sequencing, was conducted to technically validate the approach and identify potential savings. We found for these patients that the GEMINI pathway was less expensive by approximately 8% than their original diagnostic pathway.

We then estimated that the mean cost of testing for 143 newly referred patient samples using the GEMINI approach versus the expected cost of using a diagnostic pathway involving existing gene panels or a single gene test. Pathogenic mutations were identified in 49 of 143 patients, which resulted in a mean cost per diagnosis using GEMINI of £1897 versus £2603 had these patients received existing sequencing tests from other service providers.

This is a conservative estimate, based on treating the GEMINI pathway solely as an equivalent technology to the existing testing pathways. As we continue to work through the data we expect to see an overall increase in diagnostic yield detected by using the GEMINI approach in genes which are either currently not listed within the UKGTN testing directory or are available from specialist providers abroad but are prohibitively expensive, further reducing the mean cost per diagnosis of using a of clinical exome sequencing approach.

For details of the study, contact Dr Gurdeep Sagoo