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Australian Team Builds Federated System for Integrating Genomics Into Healthcare

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SAN FRANCISCO (GenomeWeb) – With 17 flagship genomics projects focusing on rare diseases and cancer, Australian researchers are aiming to integrate genomic medicine in a standardized fashion throughout the country.

Australia's national genomics project kicked off in 2015 with a A$25 million ($16.9 million) grant from Australia's National Health and Medical Research Council, which funded the Australian Genomics Health Alliance. Since then, the alliance has secured an additional A$130 million in funding from the various state governments and philanthropic grants and has grown to 80 partners from 47, involving 400 individual researchers. In addition, the national government last year said it planned to invest A$500 million in genomics as part of its 2018-2019 health budget.

In a commentary published last month in the American Journal of Human Genetics, members of the alliance reported on the national effort and its progress to date.

While the Australian Genomics effort is similar to other national population sequencing projects, such as the UK's 100,000 Genomes Project, one main difference is that its team has structured the program with clinical integration at the forefront.

Just before the project launched, a number of initiatives spearheaded by various states in Australia had started, said Kathryn North, head of Australian Genomics and director of the Murdoch Children's Research Institute at the University of Melbourne.

But as some states and research organizations began investing in genomics research and seeing the benefits of using sequencing to diagnose rare disease in particular, stakeholders realized that "it would be a major threat if each individual state continued doing things in a disconnected way," North said.

In addition, while currently, the vast majority of genomic sequencing is happening in the research setting, looking ahead at the next decade, North said it was clear that sequencing would increasingly be part of clinical care. "So, the issue is, how do you build that into a healthy system, which involves more than just building sequencing capacity but training a genomics literate workforce and the developing the ability to incorporate large data with clinical information in an ethical way," she said.

The structure of health care delivery in Australia was also a challenge and that team had to ensure that boht the federal and state governments bought it. While the federal government funds primary care, many testing services, and medicine, the state governments fund the hospital system and genetic services, North explained. But, the Australian Genomics initiative needed federal buy-in to develop a uniform system.

The goal was to avoid a situation where genomics was only used at specialty clinics or the large research institutions. Instead, she said, the aim of Australian Genomics was to develop a standardized framework for implementing clinical genomics such that everyone would have access to genomic medicine regardless of where they lived or which hospital or clinic they visited.

North, a senior author of the AJHG commentary, said the biggest challenge thus far has been developing and putting in place such a uniform, nationwide infrastructure for patient recruitment and sequencing, including informed consent, physician training, genetic counseling, and the ethical and legal framework to guide return of results, privacy considerations, and data sharing.

With that infrastructure now in place, North anticipates an uptick in patient recruitment. The initial funding from the NHMRC was intended to help recruit around 5,000 patients prospectively for the effort's 17 projects. North said just under 4,000 patients have been recruited so far and the program also recently received additional funding from the Genomics Health Futures Mission to expand its cardiovascular program and to launch a reproductive carrier screening project to screen 10,000 couples for variants in around 500 genes associated with severe genetic disorders.

"The first two years were focused on building the foundation and getting used to the model," North said. "But now there's a huge momentum."

Aside from clinical utility, the researchers will also study the economics of integrating genomics into clinical care to determine how it impacts healthcare costs and patient outcomes and to help determine in what instances or at what point in the care continuum it makes the most sense to do sequencing. 

Patients are recruited prospectively at 30 different sites across the country. Depending on the project, patients receive either exome sequencing, whole-genome sequencing, RNA-seq, a gene panel, or some combination. Patients are enrolled when it's determined that a genomic test would be warranted. "So, it's part of their clinical care, but at the same time, they are also consented for the research that goes along with it," North said. "The goal is to mimic what would happen in clinical practice."

Because the testing includes both clinical care and research, patients are consented at different stages. The initial analysis — whether the test is WGS, exome, or panel sequencing — is focused on the specific clinical condition. For instance, in patients with a neuromuscular disorder, it will focus only on the subset of genes relevant for those conditions and patients receive any diagnostic information it reveals.

In addition, patients can also consent to receiving additional findings not related to their condition. "That's a separate consent with a separate physician's visit because it requires a different type of genetic counseling compared to when a physician is doing the test to contribute to a patient's diagnosis," North said. "We're mimicking what would happen in clinical practice," she said, with testing for a specific condition done first.

The researchers are also studying whether patients decide to receive those additional findings as well as whether and how such findings add to the utility of testing. "That's a very important question to answer," she said.

In the future, as Australia further implements genomics into medical practice, North said she envisions genomics will become a standard part of practice and will include both centralized testing facilities as well as decentralized testing, depending on the specific condition. For instance, for something like neonatal sequencing, where the sequencing lab is essentially running 24 hours a day to be able to deliver results quickly, she anticipated that testing would be centralized at just a couple of locations. But for other conditions, like cancer, she envisioned pathology laboratories all over the country would have their own capabilities. However, "the goal is that everyone will use the same infrastructure," she said.

North cited two flagship projects that are serving as models.

One project, known as Acute Care Genomics, is focused on rapid whole-genome sequencing to diagnose critically ill newborns and infants. The project kicked off in 2018 and involves 12 of 13 neonatal intensive care units and all six pediatric ICUs in Australia.

"It's a national approach to acute care," North said, with the goal of ensuring that all critically ill newborns across Australia receive the same care. The team's whole-genome sequencing protocol has a turnaround time of as little as five days. North said the researchers are now working on publishing the results from the first 100 cases.

Another project that has seen rapid growth is focused on kidney disease. The KidGen Collaborative has completed recruitment of 200 participants for one of its kidney genetics flagship projects and launched a second project, HIDDEN, which will use whole-genome sequencing for adults and children with end-stage kidney disease of unknown but suspected genetic cause. There are now 17 renal genetics clinics throughout Australia that cover every state, as well as the Northern Territory.

North said the establishment of the network of clinics has enabled researchers to develop a pipeline for gene discovery research as well.

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