Purpose: We conducted a systematic literature review to summarize the current health economic evidence for wholeexome sequencing (WES) and whole-genome sequencing (WGS).Methods: Relevant studies were identified in the EMBASE, MEDLINE, Cochrane Library, EconLit and University of York Centre for Reviews and Dissemination databases from January 2005 to July 2016. Publications were included in the review if they were economic evaluations, cost studies, or outcome studies.Results: Thirty-six studies met our inclusion criteria. These publications investigated the use of WES and WGS in a variety of genetic conditions in clinical practice, the most common being neurological or neurodevelopmental disorders. Study sample size varied from a single child to 2,000 patients. Cost estimates for a single test ranged from $555 to $5,169 for WES and from $1,906 to $24,810 for WGS. Few cost analyses presented data transparently and many publications did not state which components were included in cost estimates. Conclusion:The current health economic evidence base to support the more widespread use of WES and WGS in clinical practice is very limited. Studies that carefully evaluate the costs, effectiveness, and cost-effectiveness of these tests are urgently needed to support their translation into clinical practice.Genet Med advance online publication 15 February 2018

countries and countries with similar level of economic development. ReSultS: The cost per QALY CET was estimated at 19%-66% of GDP or USD 513-1,782. The updated WHO recommendation on setting CET indicated that local data needs to be taken into account and that the 1-3 GDP per capita threshold should not be used as a rule of thumb, as this can potentially lead to a wrong reimbursement decision and forgone health. ConCluSionS: The local analysis of effects of health care expenditures on health gains can't be performed due to lack of detailed country level data in Ukraine. As of 2018 the results reported by Ochalek et al. (2015) is a sole source of CET data for Ukraine. Multi-criteria decision analysis frameworks have also been suggested by WHO. Ukraine should consider establishing a contextspecific process for decision-making that is supported by legislation, has stakeholder buy-in and is consistent, fair and transparent.

The translation of genome sequencing into routine health care has been slow, partly because of concerns about affordability. The aspirational cost of sequencing a genome is $1000, but there is little evidence to support this estimate. We estimate the cost of using genome sequencing in routine clinical care in patients with cancer or rare diseases. Methods: We performed a microcosting study of Illumina-based genome sequencing in a UK National Health Service laboratory processing 399 samples/year. Cost data were collected for all steps in the sequencing pathway, including bioinformatics analysis and reporting of results. Sensitivity analysis identified key cost drivers. Results: Genome sequencing costs £6841 per cancer case (comprising matched tumor and germline samples) and £7050 per rare disease case (three samples). The consumables used during sequencing are the most expensive component of testing (68-72% of the total cost). Equipment costs are higher for rare disease cases, whereas consumable and staff costs are slightly higher for cancer cases. Conclusion: The cost of genome sequencing is underestimated if only sequencing costs are considered, and likely surpasses $1000/ genome in a single laboratory. This aspirational sequencing cost will likely only be achieved if consumable costs are considerably reduced and sequencing is performed at scale.