In November 2019, the Royal Court of Justice in London heard a case in which a woman, ABC, claimed three NHS trusts had been negligent in failing to tell her about her father’s Huntington’s disease diagnosis.
Back in 2009, whilst serving a hospital order for the manslaughter of his wife, ABC’s father was diagnosed with Huntington’s disease. This meant that his two daughters had a 50 percent chance of having inherited the disease-associated mutation and developing the disease. When one of his daughters became pregnant, doctors sought his consent to break confidentiality and tell his daughter of the diagnosis. However, he consistently refused, citing the reason as fear for her mental health or that she may seek a termination.
ABC later accidentally found out about her father’s condition and was diagnosed with the disease herself in 2013.
As part of her claim ABC said that the NHS owed her a “duty of care”, highlighting one of the most significant discussions in the ethics of genetic testing. What are the legal, professional and ethical, duties or responsibilities of researchers and clinicians in handling genetic testing and the knowledge that might be gained from it?1
In a research setting
Genetic testing can frequently be carried out in a research setting. What could be the duties of the researchers involved?
Case study 1
Ruby is a 4-year-old child who has a rare disease with an unknown cause, although it’s thought to be genetic. The doctor in charge of Ruby’s care recommends a research study being conducted at the hospital; the researchers are sequencing the genomes of individuals with rare diseases in the hopes of better understanding their condition and potentially providing a diagnosis.
Although Ruby’s condition is manageable, her parents hope that a diagnosis may help to further improve her care and quality of life, and so agree to take part in the study.
Taking blood samples from Ruby and her parents, researchers then sequence and analyze Ruby’s genome, comparing it to her parents’ genomes for variations that could be associated with the symptoms she exhibits. Unfortunately, they do not identify any mutations that provide an explanation.
However, the researchers also notice that in Ruby’s MLH1 gene, there is a variation that has been linked to Lynch syndrome, a condition associated with an increased risk of developing certain cancers.
The variation found in Ruby’s genome is what is known as a “secondary finding” – whilst its identification may not have been the main goal of the test, its presence was actively sought. It’s also possible to make “incidental findings”, ones which are also unrelated to her current condition, but which they cannot help but see. A 2013 report from the Presidential Commission for the Study of Bioethical Issues proposed that researchers have the following duties in genomic testing:
- To consider the incidental or secondary findings that could emerge from testing
- To develop a plan for how to communicate secondary results to patients if they do arise
- To inform research participants of the possibility of incidental and secondary findings and the plan for returning them2
The American College of Medical Genetics recommends the following for clinical labs; as part of the routine sequencing and analysis process, labs should look for variations other than those related to the indication the sequencing was ordered for, albeit from a specific list of so called “actionable” genes (including MLH1). If they do find such variations, it is suggested that they should be reported back to the clinician.3
Nevertheless, when it comes to research, do researchers have a duty to feedback any data at all to participants?
I don't think there's a single answer to that,” says Anneke Lucassen, professor of Clinical Genetics at Southampton University.
“Lots of cohort research studies take different approaches,” she continues. “For example, the UK Biobank has a very clear policy of giving no feedback, whereas some newer cohort studies tend to start with the assumption that you should give some feedback to participants. However, given that there are thousands of potentially disease-associated findings per person, this is not necessarily as clear as it sounds.; but for me, that actually is not at all clear because it depends on what it is that you're wanting to feed back.”
Note that the researchers also didn’t identify any mutations that could have caused Ruby’s condition; this isn’t an uncommon situation and doesn’t rule out a genetic explanation for Ruby’s condition. The more genomic data we gather, the more we might be able to reinterpret Ruby’s genomic information over time. A variation previously thought to be benign could actually be pathogenic or vice versa. Does this mean that researchers have a duty to re-contact participants or patients, or perhaps their clinicians, with new or updated information?
Even where new interpretations appear over time, it’s rare that they provide quick clear answers to the clinical question. Novel interpretations need to be confirmed in other patients, and that takes time. As a result, it may not be as clear cut as it sounds to say that participants or patients have a right to their research information.
“If you think that genetic information is clear-cut, then it's easy to see why people might say ‘Well it's my right to get my information back’. Whether you start from a more realistic position, that much of what we find in our genetic code is far from clear, then in that context, you might feel less of a duty to report back to your participants,” Lucassen tells me.
Many aspects of genetic testing are complex, context dependent and caveats affect significance.
“In genomics, the line between research and clinical practice is becoming ever-blurrier – it's really hard to decide ‘Is it research or is it clinical practice?’ It’s much more likely to be a hybrid of the two. Once it becomes a hybrid of the two, it's often really difficult to know which set of rules or governance structures (research ethics approval or good clinical practice, for example) you draw on to decide what to do in that particular situation.”
Clinicians – balancing duties of care
The duties of clinicians and researchers are slightly different. Researchers respect the autonomy of participants to consent to research or not, whilst clinicians have a duty of care towards their patients. Although both need to respect patients’ or participants’ confidentiality, there may be greater tensions surrounding this in the clinical setting, since patients are seeking answers to clinical questions rather than taking part in altruistic research. Again, there are caveats – see above where Ruby takes part in a hybrid activity, that of clinical research. Her parents do expect to hear back from the research they have recruited her to.
During the consent process, clinicians have a professional responsibility to discuss the possible outcomes and consequences of a genetic test, including what it could mean for a patient’s family members and the possibility that the family may have to be told about their own risks. This might, in extreme circumstances, involve breaking confidentiality. Lucassen tells me that, more often than not, a patient will be involved in telling their relatives, or relatives could be told general information which does not break someone’s confidence.
Case study 2
Patricia is a 45-year-old patient who has developed breast cancer; she’s tested for BRCA1 and BRCA2 mutations as this can tell the doctors more about her cancer and how best to treat it. Mutations in BRCA genes are often associated with an extensive family history of breast and/or ovarian cancer, which is true of Patricia’s family.
Genetic counselor Joyce Turner, MSC, CGC, gives an overview of BRCA genes and their relationship to breast and ovarian cancer, and explains more about the testing process for BRCA mutations.
The test results come back and Patricia carries a mutation in BRCA1 known to be related to breast and ovarian cancer.
Patricia also has three children, all of whom have a 50% chance of having inherited the BRCA1 mutation. The same goes for any of her first-degree relatives. If any of these family members have inherited the mutated copy of the gene, they could also be at high risk of developing the disease.
What if Patricia doesn’t tell her children of their risks? This is highly unusual, but clinicians wouldn’t be breaking the law by telling Patricia’s children that they are at risk. “My responsibility to my patients is to keep their private information private, as much as I possibly can,” says Lucassen, “But my duty of confidentiality is not absolute. It's not in any clinical situation. And there are certain reasons why I might need to breach confidentiality, and that's if I can demonstrate that I will prevent significant harm in another person, and that on balance that harm is greater than the harm to a patient from a breach of their confidence.”
But Lucassen adds: “I think in genetics we often don’t need to pile into a breach of confidence. In this example, if we don’t have Patricia’s consent to telling her children about their possible inheritance, then we might just tell them they are at risk of an inherited condition. We don’t need to tell her children anything about Patricia, we could limit ourselves to saying, ‘We have reason to believe you are at increased risk of an inherited condition’. To Patricia I might say, ‘I won’t tell anyone private information about you, but I may need to tell family members about their familial risk’.
“So it would be a bit like contact tracing – I could contact those I know to be at risk (and am able to contact) and let them know that they're at risk of something without explaining why I know that. I don’t believe this is a breach of confidence, even if the children go on to make some inferences about whom they may have inherited something from.”
Professor Lucassen tells me that there can be an interesting difference between clinicians and patients as to what they think is the right thing to do in such a situation:
“I think that actually, the public is much more in tune with the implications of genetic testing than health professionals sometimes are.
“Our research has shown that health professionals are often quite rigid in their approach about confidentiality and say that their patients would expect them to be so. These health professionals might feel relatives ought to be alerted but don’t do so for fear of repercussions from the index patient.
“However, most patients and publics will say, ‘Oh gosh, if I was in that situation, I'd expect my health professional to let me know about that, or I'd expect my health professional to let my relatives know if I had a health condition.’”
What are the possible reasons for this difference?
In Lucassen’s opinion, the discrepancy is the result of an increasing focus of medicine on the individual in recent decades, with most specialties exclusively dealing with the patient in front of them. With the advent of genetic medicine, medical professionals can now be exposed to genetic test results that make them aware of potential health implications for patients’ relatives. “We usually ask our patient to share that information with their relatives, but we know that it often doesn’t happen, or indeed that patients ask us to do that for them. 21st century medicine is not well set up for this particular type of contact tracing.”
How do we clarify duties in genetic medicine?
“I think, increasingly, professional guidelines will urge us to think about familial approaches to confidentiality, rather than individual confidentiality,” says Lucassen.
The key to how healthcare professionals interpret such guidelines is likely to be interdisciplinary collaboration and discussion.
In 2001, Lucassen co-founded the Genethics Forum – this is a triannual, multidisciplinary event in which UK health professionals, medical lawyers, ethicists and other interested parties, come together to discuss the ethical and/or legal issues encountered in their genetic medical practice throughout the UK. What was originally planned to be a one-off meeting has turned into more than 50 thus far, and with the increasing use of genetic testing in healthcare, it seems important that such professional support continues.
“These meetings are so interesting,” Lucassen explains, “Because particular questions arise repeatedly, yet often with a slightly different nuance and context, so that each time we need to think about how to interpret professional guidance or the law and decide what is the best way to manage this particular complex situation.
“We realized early on that multidisciplinary discussions of these complex contextual issues provided support for health care professionals and has helped to shape good practice.”
- Middleton et al. (2019). Should doctors have a legal duty to warn relatives of their genetic risks? The Lancet. DOI: https://doi.org/10.1016/S0140-6736(19)32941-1
- (2013). Anticipate and communicate: ethical management of incidental and secondary findings in the clinical, research, and direct-to-consumer contexts. Washington, D.C.: Presidential Commission for the Study of Bioethical Issues.
- Green et al. (2013). ACMG recommendations for reporting of incidental findings in clinical exome and genome sequencing. Genetics in Medicine. DOI: https://doi.org/10.1038/gim.2013.73