'Ethical and practical implications of returning genetic research results: two Australian case studies' by Jane Tiller, Alison H Trainer, Ian Campbell and Paul A Lacaze in (2020) Medical Journal of Australia comments
Should medically significant genetic results be offered to research participants or their at‐risk relatives?
Australian research studies now generate genetic information on thousands of participants. Some genetic results, present in a small portion of participants (< 5%), are considered medically actionable, meaning they are associated with increased risk of adult‐onset diseases, where effective risk management, prevention or treatment exists (eg, inherited cancer or cardiac disorders). The National Statement on Ethical Conduct in Human Research, which considers genomic research at Chapter 3.3, now requires an ethically defensible plan for return (or non‐return) of genetic research results. Box 1 summarises the guidelines that are relevant to the return of genetic results to research participants.
Returning genetic research results can be life‐saving, alerting participants to preventive steps that they would not otherwise have taken. Most participants identified in research studies have no clinical features or family history of the indicated disease, are unaware of their genetic risk, and would not qualify for publicly funded clinical criteria‐based genetic testing.
Among the international genomics community, there is growing consensus that medically actionable genetic research results should be made available to participants. The American College of Medical Genetics and Genomics published a list of genes related to medically actionable conditions, in which results should be returned if identified during clinical testing. This gene list has been used to guide the return of research results in some United States studies, but has not been adopted by the National Health and Medical Research Council or other Australian bodies. However, the National Statement makes it clear at 3.3.41 that “researchers have an obligation to have a process in place for the return of findings that are of proven validity and of health significance to the participant, or relative, subject to participant consent”.
However, even where participant consent has been obtained, not all Australian studies are returning medically actionable results, due to varying ethical and practical challenges. For example, research participants may provide samples for altruistic reasons, before research analysis, without expectation of re‐contact. Should results be returned to these individuals, especially those unaffected by indicated disease? Is there a legal or ethical requirement to make results available or liability for withholding them? The National Statement provides some guidance (Chapter 3.3) regarding which results should be returned, but ultimately researchers determine whether to return results.
As the National Statement indicates, return of results should be limited to those genes with validity and utility (3.3.29 and 3.3.41). However, pathogenic variants in medically actionable genes are not fully penetrant, meaning that not all at‐risk variant carriers develop the disease. Risk estimates for many genes are still uncertain, complicating decisions around medical actionability and the time frame for returning results. Some participants may experience surprise or distress on learning about genetic risks. Returning results may also raise the possibility of out‐of‐pocket medical costs or increased insurance liabilities for younger participants. Genetic results should be delivered by a medical professional, with genetic counselling and clinical support provided, as noted by the National Statement (3.3.31 and 3.3.32). This requires time and resources, which are often limited.
Thus, despite clear guidance in the National Statement, some research studies do not return results even where results are clinically valid and of undisputed relevance to participants’ and family members’ health, and the participant has consented to receive such results. To assist with these challenges, a national service to support the return of genetic results from research studies has recently been developed and is now operational.