A recent article in Healthy Debate highlighted the possibility of uncovering incidental findings as a significant challenge in genomic sequencing. An incidental finding is a genetic condition that causes a disease unrelated to the reason genetic testing was initially ordered.

For example, imagine you have been recently diagnosed with a serious disease, such as colon cancer. Your doctor recommends genomic sequencing to understand if there is a hereditary genetic cause of the disease called Lynch syndrome. Finding out if you have Lynch syndrome is important because children can inherit the condition from their parents. There are standard, less expensive genetic tests that can tell you if you have Lynch syndrome. But genomic sequencing is better at identifying if you have Lynch syndrome compared to standard testing.

Because genomic sequencing looks at many genes, in addition to finding out about your colon cancer, the test may also discover you’re at risk for other diseases, such as Alzheimer’s or Long QT syndrome. Long QT syndrome causes the heart to beat very fast and can lead to fainting, seizures or sudden death. The difference between Alzheimer’s disease and Long QT syndrome is that Long QT syndrome can be treated, but the treatments for Alzheimer’s aren’t very good.

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The decision about whether or not you would want to know about these incidental findings is complex. If you’ve just learned you have colon cancer, which would cause considerable worry, would you also want to find out your risk for other diseases at the same time? Would it matter if they were treatable? What if there were no good treatments available? The issue has been debated in medical journals, and my colleagues and I recently surveyed people on their preferences. The difference between what medical experts recommend and patients’ preferences must be addressed.

The experts have had their say

An American College of Medical Genetic and Genomics (ACMG) working group recently published a list of the genetic conditions they thought should be examined by laboratories and returned to patients through their doctor, if the patients test positive for them. The list was developed largely using the opinion of medical and laboratory geneticists.

The ACMG list only includes genetic findings that are likely to cause a particular disease. And each selected genetic condition is associated with a disease that has effective medical treatment. The ACMG statement did not support allowing patients to decide whether or not incidental findings from the list are reported to them. Their reasoning was that the level of genetic counselling needed before a patient could make an informed choice could be overwhelming to the individual and costly to the health-care system. The working group also suggested doctors and laboratory personnel have a duty to prevent potential harm by telling patients about incidental findings. As such, the group recommended  doctors discuss the possibility of incidental findings with patients before genomic sequencing is conducted. Patients can then decline genomic sequencing if they prefer to not receive information about incidental findings. In such a situation, the patient would be offered standard genetic testing that cannot identify incidental findings.

The ACMG guidelines were controversial because of their all-or-none nature. However, in April 2014, the ACMG statement was amended to recommend providing an opt-out option for patients who don’t want to receive any information on incidental findings. In this case, patients would still undergo genomic sequencing instead of being only allowed standard genetic testing. However, patients still cannot select which specific incidental findings they want to learn about.

Patients and society should have their say

Researchers who specialize in person-centered health care believe it’s important to understand individuals’ preferences to guide choices in medical care. As it turns out, understanding preferences to guide policy is a central theme of economics. Economists use the concept of utility to represent preferences. Utility can be understood as a representation of a person’s well-being. In health care, it’s measured by observing the choices individuals make between options.

For example, one option could be to only receive information about incidental findings that have a high risk of occurring and for which there are effective medical treatments available. An alternative option would be to receive information about diseases with a high risk of occurring whether or not there are effective medical treatments. Yet another would be to opt out of receiving any incidental findings, regardless of potential health implications. When an individual chooses a particular option, it is assumed they chose the alternative that will give them the greatest amount of well-being.

When a policy is new and not yet widely implemented, it’s difficult to observe the actual choices of patients. In these circumstances, researchers can create surveys to ask individuals what they would choose in certain situations. The survey we created was given to the general population across each province and territory in Canada.

What do Canadians think?

Making a choice between health-care alternatives can be difficult. Before we asked people what they thought, we presented them with a short video introduction to the survey.

As you can see from the video, we were interested in how Canadians value knowing the risk of acquiring the incidental disease at some point in the future, and whether this choice was influenced by whether the disease is treatable. We also wanted to understand if their choice depended on how severe the incidentally identified disease is, and the out-of-pocket cost they would need to pay to receive information on incidental findings. Finally, we found out whether respondents wanted information about whether they are a genetic carrier of a disease. Carriers don’t get sick with the genetic condition, but when both parents are carriers, they can pass the condition on to some of their children, who will get the disease (sickle cell disease is an example).

In all, 1,200 respondents across Canada completed the questionnaire. We found they were more likely to want to know about incidentally identified diseases if they were at high risk of developing the diseases than if they were at a lower risk of developing them. Respondents also wanted to have a choice about the type of information about incidental findings they receive, including a choice of only receiving information about treatable diseases or whether or not they receive information on their carrier status. In addition, we found that not all individuals want information on incidental findings.

What’s next?

The most significant implications of our research is that we need to find a way of giving patients a choice about what incidental findings are given to them. We found that giving individuals a choice about which incidental results are returned, if any, will increase the overall well-being of society compared with restricting the choice to a list created by medical experts.

The ACMG’s list of incidental findings will be used to guide practice in Canada. In the near future, it will likely expand to include many more genes that are associated with diseases. It’s our hope that decision makers and the ACMG will consider our research and include patient choice as an important aspect of returning incidental findings from genomic sequencing.