Participant experiences of genome sequencing for rare diseases in the 100,000 Genomes Project: a mixed methods study

Abstract

In this mixed methods study, a survey and in-depth interviews were used to explore whether decision regret and the psychological impact of receiving genome sequencing (GS) results differed between parents and patients, and between those who received a genetic diagnosis and those who did not. Participants (n = 77) completed a survey that included the Decisional Regret Scale (DRS) and an adaptation of the Multidimensional Impact of Cancer Risk Assessment (MICRA) at least 12 months after consenting for GS for rare disease diagnosis in the 100,000 Genomes Project. Survey participants were invited to take part in an interview and 39 agreed; 12 with a diagnosis, 5 with variants of uncertain significance, and 19 with no pathogenic findings identified. Both survey and interview findings indicated that decision regret was low. DRS scores revealed no differences in levels of regret between parents and patients, or between those with a diagnosis and those without. Though MICRA scores indicated minimal evidence of negative psychological impacts of receiving GS results, subscale analysis revealed greater distress and uncertainty for parents compared to patients. Receiving a diagnosis was found not to influence MICRA scores, supporting interview findings of both positive and negative emotional and psychological impacts irrespective of a genetic diagnosis. Our findings have implications for policy and practice as GS is integrated into the UK and worldwide; notably, that expectation-setting is critical when offering GS, and that post-test counselling is important regardless of the GS result received, with parents perhaps needing additional emotional support.

A qualitative evaluation of patient and parent experiences with an undiagnosed diseases program

“…Specifically, participants were unsure whether they were supposed to remain in contact with the UDP and/or felt like the UDP had not explored every possible option to find a diagnosis. Those who remained undiagnosed also expressed disappointment with the lack of diagnosis, similar to previous studies (Mollison et al, 2019; Peter et al, 2022). However, other research indicates patients and parents of patients felt receiving genome sequencing (GS) or exome sequencing (ES) was the final option for them, with individuals experiencing closure whether or not they received a diagnosis (Halverson et al, 2016; Liang et al, 2021; Mollison et al, 2019; Rosell et al, 2016).…”

“…Additional studies of UDN participants have focused on specific psychosocial characteristics, including anxiety, depression, and empowerment. Patients and parents of patients were given surveys to assess these psychosocial characteristics, which showed lower empowerment scores in adults with undiagnosed diseases compared with parents of children with undiagnosed diseases, as well as higher rates of anxiety, depression, stress, and helplessness in parents of children with undiagnosed diseases (Aldiss et al, 2021; McConkie‐Rosell et al, 2018; Palmer et al, 2018; Peter et al, 2022). These findings are similar to those of individuals with diagnosed genetic conditions and provide an initial impression of the psychosocial characteristics of the rare disease population.…”

Hope, but never expect? Comparing parents' pre‐ and post‐disclosure attitudes toward return of results from diagnostic exome sequencing for their child

“…The reasoning they offered for this was that they had had high expectations that a diagnosis, or at least a VUS, would be achieved with WES. The finding that disappointment occurs, or even increases, when persons have heightened or unrealistic expectations about the type of result they will receive, is consistent with insights of other empirical studies and points to acknowledging expectation management as part of the informed consent process (Bos & Bunnik, 2022;Donohue et al, 2021;Eichinger et al, 2023;Peter et al, 2022;Wynn et al, 2018). However, our results show that this observation should be built upon further, since parents who adopted a hopeful stance about what WES might offer them reported being ultimately more satisfied with the whole sequencing experience than the couple in our study who expected a certain outcome or answers from WES and thus reported being disappointed.…”

Trust in prenatal exome sequencing for expectant families facing unexplained fetal anomalies

“…Existing studies have suggested that patient concerns include data protection, privacy, and lack of definitive clinical answers 12,13 . Outside the prenatal setting, it has been shown that parents and children taking part in ES for the 100,000 Genomes Project have positive views on research, data sharing, and the healthcare system 13 .…”