Views of rare disease participants in a UK whole-genome sequencing study towards secondary findings: a qualitative study

Abstract

With large-scale genome sequencing initiatives underway, vast amounts of genomic data are being generated. Results—including secondary findings (SF)—are being returned, although policies around generation and management remain inconsistent. In order to inform relevant policy, it is essential that the views of stakeholders be considered—including participants who have made decisions about SF since the wider debate began. We conducted semi-structured interviews with sixteen rare disease patients and parents enroled in genome sequencing to explore views towards SF. Informed by extensive contact with the healthcare system, interviewees demonstrated high levels of understanding of genetic testing and held pragmatic views: many are content not knowing SF. Interviewees expressed trust in the system and healthcare providers, as well as an appreciation of limited resources; acknowledging existing disease burden, many preferred to focus on their primary condition. Many demonstrated an expectation for recontact and assumed the possibility of later access to initially declined SF. In the absence of such an infrastructure, it is important that responsibilities for recontact are delineated, expectations are addressed, and the long-term impact of decisions is made clear during consent. In addition, some interviewees demonstrated fluid views towards SF, and suggestions were made that perceptions may be influenced by family history. Further research into the changing desirability of SF and behavioural impact of disclosure are needed, and the development and introduction of mechanisms to respond to changes in patient views should be considered.

Parents’ motivations, concerns and understanding of genome sequencing: a qualitative interview study

“…This included misunderstandings about what types of conditions were included on the list of secondary findings (participants were informed they would learn about clinically 'actionable' findings, which was the term used in the consent form, however, we have observed that consenters did frequently cite 'cancer' and 'heart disease' during consent appointments [28]), as well as whether they had personally opted to receive to secondary findings. These findings are consistent with a previous UK study in which many participants couldn't recall their decision about secondary findings at the time of consent [15]. Where our findings add to the existing research is that we also found that several parents felt it was overwhelming to have the conversation about secondary findings at the same time as the conversation about the main findings.…”

“…However, participants' main concern about secondary findings was the potential psychological harm that the results might have on them. This concern has been identified in previous qualitative research [12,15]. In our previous observational study [28], most of the consent conversation was dedicated to providing patients with biomedical information and information about the project, e.g.…”

“…A few recent qualitative interview studies have started to shed light on the perspectives of parents who have been offered genomic (exome or genome) sequencing to diagnose their child's rare conditions in the UK [15], US [16,17], Canada [18] and the Netherlands [19]. These studies have highlighted common motivational factors for consenting to genomic testing such as desire for a diagnosis and contributing to science [16], but have also identified concerns around elevated expectations and loss of hope for recovery following a diagnosis [17].…”

Parents' perceptions of diagnostic genetic testing for children with inherited retinal disease in China

“…Similar qualitative studies have explored parents’ attitudes toward childhood genetic testing for cancer (Alderfer et al, ; Bradbury et al, ; Godino, Jackson, Turchetti, Hennessy, & Skirton, ), autism spectrum disorders (Chen et al, ; Chen, Xu, Huang, & Dhar, ), and deafness (Mackley et al, ) in Western countries. This is a qualitative investigation that has explored parents’ in‐depth opinions toward genetic testing for IRDs in a Chinese population.…”

“…Our findings revealed that parents with low educational levels and annual household incomes tended to have relatively low levels of knowledge and awareness of genetic testing. Most published studies on genetic testing for children had focused on highly educated parents in high‐income countries (Alderfer et al, ; Chen et al, ; Lim et al, ; Mackley et al, ), and we approached this important topic in a very different environment.…”