Appendix 5Summary of findings – cost-effectiveness of next generation sequencing
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| First Author, Publication Year | Main Study Findings | Authors’ Conclusions |
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| Health Technology Assessment |
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| Foundation for Genomics, and Population Health,4 2011 | Sanger sequencing has a low error rate though not at 0 (error rate at 1 in 1000–10000 bases) for individual gene runs but when a condition where variants are found in a heterozygous gene set is discovered analysis is extremely difficult.
Sanger sequencing is expensive at ~$500/Mb compared to less than $0.50/Mb for NGS platforms.
Cost of WES for examination of colorectal cancer in United Kingdom varies greatly from laboratory to laboratory (e.g. Cost for single test ranged from £430 up to £1050). Additionally the time to produce the clinical report varied from 40 days up to 80 days. |
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It is not the responsibility of the health-care system to investigate variants detected in genes outside of the initial analysis agreed to by the patient. - -
Effort should be taken to reduce the amount of incidental variants detected unless they are believed to have the potential to cause dramatic health effects. - -
There is a lack of randomized controlled trials to analyze the cost and benefits associated with WGS in clinical and research settings. This is a result of all economic evaluations lacking any “real” information on how the increased variant detection in ambiguous genes from NGS runs impacts the health-care system. - -
Currently there is a lack of economic evaluations on NGS applications that effectively examine association between diagnostic evaluation and endpoint patient diagnosis. - -
In situations where NGS is not currently being used then the implementation of an NGS pathway is not recommended due to the expense of initial start-up costs.
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| Systematic Reviews |
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| Frank et al.,1 2013 | Sanger sequencing is most expensive process being used (1Mb costs ~$500 therefore to sequence entire human genome will cost ~$1.5 million per patient)
Prices vary from laboratory to laboratory, closest estimates are:
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Roche/454 GS FLX Titanium platform costs $12.40 to $84.39 per Mb - -
Illumina HiSeq2000 is least expensive and costs ~0.10/Mb therefore whole genome is estimated at ~$300 for WGS process
Expenses associated with sequence analysis/filtering/data management are typically higher than actual sequencing process. These processes are most expensive for platforms that use short read length.
Data storage is major concern as a single WGS run will result is 2.5 terabytes of hard disk space.
Currently the risk of false positive results cause a requirement for confirmation testing especially in cases of a recessive disorder (these have a compound heterozygote) |
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It is extremely difficult to estimate costs associated with processes after actual sequencing run as they require multiple different professionals from molecular and computational biologists to genetic counsellors, pathologists and clinicians. - -
May be more cost effective to reanalyze a patient than to store the data from a previous run due to expense of data storage equipment (stipulated that this is for current dates only as prices for this type of equipment are rapidly dropping). - -
The need to confirm NGS results using established methods will not be required in near future as protocols for these processes are rapidly becoming more robust and reliable. - -
Results from a WGS run are still quite complex and the transition of the data to a patient is equally as multifaceted since every person has a different view of what will be a concern. - -
Stipulate that the industry is still far from the $1000 genome and even if it is reached it will still cost ~$600 million per year to sequence every child born in Germany.
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| Sullivan et al.,5 2012 |
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In the United Kingdom it costs ~£600 for proband and £120 for family member of a person already carrying a BRCA1 or BRCA2 mutation using Sanger sequencing - -
Standard test currently used for analysis of BRCA1 and BRCA2 in United Kingdom is Sanger sequencing followed by MLPA* though two laboratories utilize NGS processes - -
Authors cannot state NGS is cost effective due to a lack of sufficient robust evaluation
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There is a lack of sufficient economic evidence to support or deny the switch to NGS or keep standard Sanger-MLPA processes. - -
Currently there are programs in the European Union to establish NGS in clinics, these are; TECHGENE, EURO-GENE-SCAN and NMD-CHIP
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MLPA – multiplex ligation-dependent probe amplification
