Whole-exome sequencing in clinical genetics : A health economic evaluation

The budget impact and cost-effectiveness of introducing whole-exome sequencing-based virtual gene panel tests into routine clinical genetics

Authors: Gurdeep S Sagoo, Gail Norbury, Shehla Mohammed, Mark Kroese Funding and acknowledgements: PHG Foundation would like to thank Guy’s and St Thomas’ NHS Foundation Trust for funding this work. We would also like to thank Prof Sean Whittaker, Dr Melita Irving and all the laboratory and clinical staff at the South East Thames Regional Genetics Service for their valuable contributions to the pilot study.


Harnessing academic and clinical expertise within King’s Health Partners (KHP), the KHP Biomedical Diagnostic Hub is working to establish the routine clinical use of next generation sequencing (NGS) technology across the NHS in order to enhance diagnostic and treatment pathways for patients with both rare and common genetic disorders.

Research question

Does the use of exome sequencing for diagnostic testing in constitutional genetics across a range of clinical scenarios and genetic disorders represent a cost-effective use of NHS resources in patients where diagnosis is currently difficult, prohibitively expensive and unavailable in the required time scale or would require invasive procedures?

The study

The study comprised 96 patients selected from a service pilot (2014-2016) for their complex clinical presentations, which were assessed as having a high probability of being an inherited disease. Two scenarios were presented:

1.y The exome sequencing-based virtual gene panel test is offered in addition to the genetic tests already conducted

2.The exome sequencing-based virtual gene panel test is presented as the ‘near’ first-line test (in addition to any standard reflex first-line tests such as array CGH for developmental delay for example)


The cost of exome-sequencing based tests (and indeed other genetic tests) accounts for a significant portion of the overall budget required to attempt to establish a diagnosis in these 96 patients. The usual testing strategy will always be the cheapest option (where exome sequencing is not used) except if in scenario 2 the cost of the genetic tests conducted and the clinical workload could be reduced in these patients. If the cost of the exome sequencing test can bring down the cost of genetic testing for these patients by £943 then the budget required to undertake the exome sequencing test as a near first-line test would be slightly cheaper (£171,593 vs £171,899) in these patients than the current usual testing pathway, with the benefit of potentially increasing the diagnostic yield (by 42.7%).


Ongoing work should focus on trying to reduce the cost of the exome sequencing test (and potentially other baseline tests conducted in addition to exome sequencing) and to investigate the assumption that clinical work up can be reduced if a positive genetic diagnosis is achieved through using such testing as a near first-line test earlier in the patient’s diagnostic journey. The experience and results of the service pilot and this economic evaluation provided the basis for the implementation of the new NHS diagnostic exome sequencing service by KHP in 2016


Acceso al documento

Please follow and like us: