Genetics

Objective To support a nationally representative group of Australians to make informed, reasoned recommendations on the use of genomics in newborn screening programmes. Design Hybrid Citizens’ Jury method. Setting, Participants Thirty Australian adults recruited by random ballot invitation and stratified selection against population-based demographic targets of age, sex, ancestry, highest level of education, location of residence (state/territory, urban/non-urban), experience of disability and parent/non-parent. Main Outcome Measures Jury recommendations with reasons. Results The jury made 11 recommendations. The jury agreed whole genome sequencing could be used in the programme, but only if conditions were met regarding national consistency, benefit, Australian Government oversight, consent, reporting to parents, data protection, supporting parents and the healthcare system, and parent and public education. All of these conditions were agreed by consensus, except reporting to parents and parent and public education, where there was a supermajority (24/30) in agreement and minority dissent. The jury were split on Recommendation 11: how much genomic data should be extracted and retained. Nine jurors supported whole genome sequencing only if data extraction and retention were limited to interpretable, actionable genetic information; 21 jurors supported a more expansive approach. Conclusions To maintain public trust in Australian newborn screening, programmes should take a more conservative approach to data extraction and storage until concerns are addressed and safeguarding conditions implemented. Jurors' key concerns include identifiability of genomic data, risk of data misuse and potential to undermine trust and participation in newborn screening.

Emma Frost, Zornitza L. Stark, Kristen Nowak, Louise Healy, Sarah Norris, Stacy M. Carter

Genomic newborn screening (gNBS) can screen for a broad range of genetic conditions, potentially enabling early treatment and improving health outcomes. However, it remains outside publicly funded programmes due to limited evidence and substantial implementation challenges. Offering gNBS in the interim as a fee-for-service option in Australia risks creating inequitable healthcare access, fragmenting care and limiting control over genomic data. Conversely, prohibiting private access may unfairly deny potential benefits to individual infants and families. This article discusses the ethical and practical implications of offering gNBS on a fee-for-service basis prior to a decision being made regarding public funding. Although fee-for-service gNBS undermines equitable access, regulated private offerings by public genomics services could mitigate some of the risks. We emphasise the need for large-scale, well-designed research studies to inform the development and equitable implementation of robust gNBS programmes within public healthcare frameworks.

Christopher Gyngell, Sebastian Lunke, Danya Vears, Zornitza L. Stark

A molecular diagnosis of monogenic diabetes can guide family planning, cascade testing and surveillance for other manifestations

Sunita MC De Sousa · Timothy ME Davis · James Harraway · Mark Greenslade · Kathy HC Wu · Ryan G Paul · Juliet Taylor · Aleena S Ali · Elif I Ekinci · Rinki Murphy · Jerry R Greenfield

The Office of the Australian Information Commissioner’s recently updated guidance clarifies clinicians’ discretion to assist patients with notifying their relatives about genetic risk without breaching federal privacy laws

Jane Tiller · Margaret FA Otlowski

A discussion on challenges in implementing genomic medicine in Australia and the role of genetic counsellors, their training and relevant skill sets. Evidence for their impact on patient care, clinicians and health services is also reviewed, with barriers to widespread facilitation.

Tatiane Yanes · Eliza Courtney · Mary‐Anne Young · Amy Pearn · Aideen McInerney‐Leo · Jodie Ingles

Substantial advances have been made associating cardiovascular disease to markers of genetic risk

Michael P Gray · Diane Fatkin · Jodie Ingles · Elizabeth N Robertson · Gemma A Figtree

Reproductive genetic carrier screening publicly available for cystic fibrosis, spinal muscular atrophy and fragile X syndrome

Alice P Rogers · Lara Fitzgerald · Jan Liebelt · Christopher Barnett

Genomic tests present additional challenges compared with other pathological investigations

Michaela Cormack · Kathryn B Irving · Fiona Cunningham · Andrew P Fennell

Both health care costs and broader societal costs should be considered when evaluating the cost-effectiveness of new therapies

Benjamin Kamien · Rachael Heath Jeffery · Fred K Chen

Melanie Bahlo

To assess the cost-effectiveness of IRD treatments, the substantial societal costs of IRDs must be considered

Deborah Schofield · Joshua Kraindler · Owen Tan · Rupendra N Shrestha · Sarah West · Natalie Hart · Liny Tan · Alan Ma · John R Grigg · Robyn V Jamieson

Timely delivery of results to guide index cancer treatment and greater equity of access are among the goals of broader testing

Stephanie M Wong · William D Foulkes

Routine testing removes barriers to testing, identifies additional women with pathogenic variants, leading to revised treatment for many

Dilanka L De Silva · Lesley Stafford · Anita R Skandarajah · Michelle Sinclair · Lisa Devereux · Kirsten Hogg · Maira Kentwell · Allan Park · Luxi Lal · Magnus Zethoven · Madawa W Jayawardana · Fiona Chan · Phyllis N Butow · Paul A James · G Bruce Mann · Ian G Campbell · Geoffrey J Lindeman

Clinically meaningful outcomes can be achieved with matched germline/tumour whole genome sequencing

The Q‐IMPROvE study group

To the Editor: O'Shea and colleagues1 have highlighted the importance of precision medicine and recognised that health care systems are struggling to adapt to new genomic innovations. New technologies are frequently distributed unevenly and follow socio‐economic gradients, and health care systems have a responsibility to ensure equitable access.2 In South Western Sydney, there is a significant population of culturally and linguistically diverse people whose genetic risk factors for cancer development and treatment are different to those of the greater Sydney population. Consequently, the Department of Anatomical Pathology at Liverpool Hospital has offered next generation sequencing (NGS), using the 50‐gene Oncomine Precision Assay (ThermoFisher Scientific) for multiple tumour streams, including non‐small cell lung cancer (NSCLC) and colorectal cancer. A nine‐month internal audit of 400 patients has found that 77% of patients with stage IV NSCLC and 82% of patients with stage IV colorectal cancer had at least one gene mutation identified using this panel. Currently, the European Society of Medical Oncology has put forward a clinical scale of actionability of molecular targets, ESCAT, to help clinicians understand the utility of genetic variations in cancer.3 The guidelines define mutations from tier I to tier X based on degree of actionability. The NGS results found that 56% of patients with colorectal cancer and 50% of patients with NSCLC had tier I mutations, defined as those with clear evidence of clinical actionability. Twenty‐one per cent of patients with colorectal cancer and 28% of patients with NSCLC had tier II or III mutations with potential actionability. In addition to providing access to standard of care treatments, NGS provides a means for patients to access novel clinical trials. In our cohort, about 45% of both NSCLC and colorectal cancer patients had additional mutations on the 50‐gene panel that are currently being investigated in early phase clinical trials. Standardisation and funding of testing across Australia is critical to prevent inequities of access to testing, especially in patients in South Western Sydney with lower rates of private health insurance, high rates of socio‐economic disadvantage and low rates of health literacy. Currently, there are a limited number of centres available in New South Wales to provide NGS testing and, thus, now is the right time to get it right for all Australians.

Udit Nindra · Abhijit Pal · C Soon Lee

Implementation science based health care research is urgently needed for genomic and precision medicine in Australia

Rosie O'Shea · Alan S Ma · Robyn V Jamieson · Nicole M Rankin

Australia should develop a sustainable evidence-based pharmacogenomic screening program, with DPYD genotyping at the forefront

Cassandra White · Rodney Scott · Christine L Paul · Stephen P Ackland

Many technical and regulatory hurdles have been overcome, but the field has a long way to go

Gabrielle O'Sullivan · Joshua G Philips · John EJ Rasko