Whole-exome sequencing in intellectual disability; cost before and after a diagnosis

Abstract

Clinical application of whole-exome and whole-genome sequencing (WES and WGS) has led to an increasing interest in how it could drive healthcare decisions. As with any healthcare innovation, implementation of next-generation sequencing in the clinic raises questions on affordability and costing impact for society as a whole. We retrospectively analyzed medical records of 370 patients with ID who had undergone WES at various stages of their diagnostic trajectory. We collected all medical interventions performed on these patients at the University Medical Center Utrecht (UMCU), Utrecht, the Netherlands. We categorized the patients according to their WES-based preliminary diagnosis ("yes", "no", and "uncertain"), and assessed the per-patient healthcare activities and corresponding costs before (pre) and after (post) genetic diagnosis. The WES-specific diagnostic yield among the 370 patients was 35% (128 patients). Pre-WES costs were €7.225 on average. Highest average costs were observed for laboratory-based tests, including genetics, followed by consults. Compared to pre-WES costs, the post-WES costs were on average 80% lower per patient, irrespective of the WES-based diagnostic outcome. Application of WES results in a considerable reduction of healthcare costs, not just in current settings, but even more so when applied earlier in the diagnostic trajectory (genetics-first). In such context, WES may replace less cost-effective traditional technologies without compromising the diagnostic yield. Moreover, WES appears to harbor an intrinsic "end-of-trajectory" effect; regardless of the diagnosis, downstream medical interventions decrease substantially in both number and costs.

Clinical Integration of Genome Diagnostics for Congenital Anomalies of the Kidney and Urinary Tract

“…WES includes all of the coding exons of the genome, which facilitates gene-panel analysis without redesign of the experiment in case of updates. A WES-based test combined with variant analysis aimed at the genes of interest is known to have multiple advances over targeted gene-panel capture and sequencing (83): (1) newly identified genes can easily be added to the analysis without adjustment and validation of the laboratory flow-because the nephrogenetics field is evolving fast, with causal genes being identified on a regular basis, a flexible approach like WES facilitates rapid test updates; (2) gene-panel analysis from WES data prevents the identification of incidental findings; (3) data on the full exome is available and can be released for further investigation in case the molecular cause has not been identified, leading to a higher diagnostic yield (84); and (4) WES results in a considerable reduction of diagnostic time and healthcare costs, especially when applied early in the diagnostic process (80,85).…”

Improving access to genetic testing for adults with intellectual disability: A literature review and lessons from a quality improvement project in East London

“…One Dutch study retrospectively examined Whole Exome Sequence data for 370 patients with ID finding a diagnostic yield of 35 and an 80% reduction in healthcare costs per patient after genetic testing regardless of diagnostic result (Vrijenhoek et al, ). However, studies using patient reported outcome measures are sparse.…”

Impacts of genomics on the health and social costs of intellectual disability

“…Along with the decreasing cost of sequencing, these improvements have facilitated the transition of genomic testing from a research endeavour to clinical diagnosis. There is limited economic evidence supporting this transition 6 11–16. The available studies that attempt to determine the cost-effectiveness of genomic testing1 12 17 18 do not employ standard methods for the economic evaluation of health technologies,19 relying on simplified assumptions to estimate cost-effectiveness, largely due to lack of data to populate the models 20 21…”