By Julia Karow
A comprehensive report released this week by the PHG Foundation, an independent UK-based non-profit health policy organization, focuses on the promises and challenges of implementing whole-genome sequencing for healthcare in the UK.
The 192-page report, available here, contains 10 recommendations for UK policy makers on how to implement genome-wide sequencing within the UK's National Health Service.
According to Hilary Burton, the foundation's director, the report was intended to inform policy advisors, such as the Human Genomics Strategy Group, which was set up two years ago by the UK's Department of Health (GWDN 12/16/2009).
The report recommends the introduction of next-gen sequencing as part of the NHS "in the short to medium term" for the diagnosis of inherited diseases and the management of cancer, where it says the technology "offers clear clinical and cost benefits over existing tests." According to Burton, this is already ongoing as targeted sequencing tests are being replaced by next-gen sequencing, but not yet whole-genome sequencing.
Only those variants that are relevant for a specific clinical condition should be analyzed and shared with patients, according to the recommendations, and genomic data should not be used in the absence of a clinical indication. This could be achieved through the use of bioinformatic filters, Burton said, which would minimize the amount of incidental findings.
The foundation cautions against looking for mutations unrelated to a clinical phenotype, even if it could be of importance for a patient's health, "because that would be getting us into the realms of opportunistic screening," she said, which requires different criteria and standards.
Clinical bioinformatics expertise and infrastructure is "urgently" needed to support the clinical use of sequence data, according to the report, which recommends that a National Biomedical Informatics Institute be established. Such an institute, which could be virtual or physical, has already been recommended by others, Burton said, for example in a report on genomic medicine prepared by House of Lords two years ago.
Along with bioinformatics expertise, the PHG Foundation notes that standardized databases of normal and pathogenic genomic variation are needed for the clinical interpretation of sequence data.
It will also be important to define the rights and responsibilities of patients and healthcare providers when it comes to whole-genome sequence data, and to develop guidelines for its clinical use. This will include, for example, what information will or will not be reported back to patients, such as variants of unknown significance or incidental findings, and whether data should be reanalyzed in light of new scientific findings. "There needs to be an explicit understanding on both sides on what will be done and what won't be done," Burton said.
Healthcare professionals need to be educated about whole-genome sequencing to understand its benefits and limitations, and guidelines for its use need to be established. This is especially important, Burton said, as the technology is being applied across a wide range of clinical specialties, and outside of traditional clinical genetics.
The report also recommends that a small number of sequencing laboratories act as "regional hubs" for the entire NHS. These could be public-private partnerships, collaborations with academic centers, or private providers.
Studies on the economic impact of next-gen sequencing are "urgently needed" to identify both its costs and savings. "We desperately need some better evidence, gained in a systematic way, that this is cost-effective," Burton said. This can be tricky, though, since it is difficult to measure the outcome of sequencing tests, which can help prevent rather than cure disease and which often affect family members beyond the patient tested.
To enable the use of next-gen sequencing in the NHS as a novel technology and not a replacement of existing tests, there need to be "commissioning processes for all the relevant services, along with other forms of genetic and genomic testing."
Finally, research is needed to see whether genome sequencing could ultimately be used as a screening tool to prevent disease.
Funding for the report, which included two workshops with stakeholders in March and June of this year, came from the PHG Foundation itself, Illumina, the University of Cambridge Centre for Science and Policy, and the Wellcome Trust.
The foundation was advised by a steering group, with members from various UK-based universities, hospitals, research institutes, and genetics laboratories.
The PHG Foundation, also known as the Foundation for Genomics and Population Health, is based in Cambridge, UK. It is funded through donations, grants from public and private sources, and a charitable endowment from an undisclosed group of individuals.
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