Study analyzes individuals’ stance on secondary genomic findings

Recent research by scientists at the National Institutes of Health (NIH) disclosed that around half of the people who refused to receive secondary genomic findings switched opinions after their healthcare provider presented them with further information.

Researchers find many people want secondary genomic findings after initially refusing. Image Credit: Ernesto del Aguila III, National Human Genome Research Institute.

The outcomes published in the journal Genomics in Medicine analyzed people’s attitudes in receiving secondary genomic findings related to preventable or treatable diseases.

The research was headed by scientists at the National Human Genome Research Institute (NHGRI) and the National Institute of Environmental Health Sciences (NIEHS), both part of NIH.

Genome sequencing is an inevitable part of clinical care, and hence, scientists and the bioethics community are examining options to navigate the discovery of secondary genomic findings.

Secondary findings resulting from genome sequencing mirror information that is distinct from the primary reason for a person’s medical care or participation in a study. For instance, the genomic data of a patient who undergoes genome sequencing to approach an autoimmune problem may disclose genomic variants linked with a heightened risk for breast cancer.

According to the American College of Medical Genetics and Genomics recommendations in 2021, people who sequence their genomes for a clinical purpose should also be screened for genomic variants in 73 genes, including BRCA1 and BRCA2—both linked to a heightened risk of breast and ovarian cancer. All 59 genes are linked with treatable or potentially severe diseases.

Supporters of an individual’s right to not know their secondary genomic findings argue that to sustain autonomy, people should have the chance to decide whether to be given information about genomic variants in these additional genes.

Because these genomic findings can have life-saving implications, we wanted to ask the question: Are people really understanding what they are saying no to? If they get more context or a second opportunity to decide, do they change their mind?”

Benjamin Berkman JD, MPH, Senior Study Author and Deputy Director, Bioethics Core, National Human Genome Research Institute

The researchers joined hands with participants from the Environmental Polymorphisms Registry, an NIEHS study analyzing the influence of genetic and environmental factors on human health. Out of 8,843 participants, 8,678 were selected to receive secondary genomic findings, whereas 165 opted out. The scientists evaluated those 165 individuals to identify how firmly and consistently they maintained their “right not to know” decision.

The scientists wanted to determine whether furnishing additional data to individuals about their genomic variants persuaded their decision and to better know why certain individuals still refused their secondary genomic findings even after receiving further information.

After the intervention, the scientists found that the 165 people were categorized into two groups—“reversible refusers” who changed their decision to accept to know their secondary genomic findings and “persistent refusers” who still refused.

It is worth noting that nearly three-quarters of reversible refusers thought they had originally agreed to receive secondary genomic findings. This means that we should be skeptical about whether checkbox choices are accurately capturing people’s preferences.”

Will Schupmann, Study First Author and Doctoral Candidate, The University of California, Los Angeles

On the basis of the findings, the scientists argue whether healthcare providers should ask individuals who have their genome sequenced to receive clinically significant secondary genomic findings. Investigators believe that ample data supports a default practice of returning secondary genomic findings without participants’ consent if they would like to receive them.

However, research works should develop a system that permits individuals who do not want to know their secondary genomic findings to opt out. The scientists suggest that when healthcare providers seek their patients’ preferences to know or not know about their secondary genomic findings, they should provide the individuals with several opportunities to make and rethink their choice.

The right not to know has been a contentious topic in the genomics research community, but we believe that our real-world data can help move the field towards a new policy consensus.”

Benjamin Berkman JD, MPH, Senior Study Author and Deputy Director, Bioethics Core, National Human Genome Research Institute

Animation of patient filling out an informed consent form and checking the “YES” checkboxes for both Expected Outcome and Secondary Findings. Video Credit: Ernesto del Aguila III, National Human Genome Research Institute.