Receiving results of uncertain clinical relevance from population genetic screening: systematic review & meta-synthesis of qualitative research

Abstract

Genetic screening can be hugely beneficial, yet its expansion poses clinical and ethical challenges due to results of uncertain clinical relevance (such as ‘cystic fibrosis screen positive, inconclusive diagnosis’/CFSPID). This review systematically identifies, appraises, and synthesises the qualitative research on experiences of receiving results of uncertain clinical relevance from population genetic screening. Eight databases were systematically searched for original qualitative research using the SPIDER framework, and checked against inclusion criteria by the research team and an independent researcher. Nine papers were included (from USA, Canada, UK, New Zealand). PRISMA, ENTREQ, and EMERGE guidance were used to report. Quality was appraised using criteria for qualitative research. All papers focused on parental responses to uncertain results from newborn screening. Data were synthesised using meta-ethnography and first- and second-order constructs. Findings suggest that results of uncertain clinical relevance are often experienced in the same way as a ‘full-blown’ diagnosis. This has significant emotional and behavioural impact, for example adoption of lifestyle-altering disease-focused behaviours. Analysis suggests this may be due to the results not fitting a common medical model, leading recipients to interpret the significance of the result maladaptively. Findings suggest scope for professionals to negotiate and reframe uncertain screening results. Clearer initial communication is needed to reassure recipients there is no immediate severe health risk from these types of results. Public understanding of an appropriate medical model, that accounts for uncertain genetic screening results in a non-threatening way, may be key to maximising the benefits of genomic medicine and minimising potential psychological harm.

Exploring the training needs of inherited cardiac conditions (ICC) nurses: Elucidating role boundaries and competencies for practice in the genomics era

“…In a systematic review, Johnson et al. (2022) concluded that uncertain results do not fit into a recognized medical model and that initial communication needs to clearly address this potential outcome of genetic testing to minimize psychological harm. Therefore, learning how to frame uncertainty should be an essential aspect of ICC nurse training.…”

Sex‐specific newborn screening for X‐linked adrenoleukodystrophy

“…For parents, receiving a result of uncertain clinical significance from newborn screening can be distressing, and this negative impact may persist when uncertainty remains unresolved. 39 At the same time, it has been well‐established that pathogenic variants in ABCD1 have no predictive value with respect to clinical outcome. This is a complicating factor in ALD disease management.…”

Informed consent for whole genome sequencing in mainstream clinics: logistical constraints and possible solutions

“…The complexity of WGS, the range of possible incidental findings, the inevitable uncertainties, and the often limited understanding about genomics by patients, their family, and sometimes by mainstream clinicians can make informed consent difficult to achieve [ 5 , 6 ]. Some have argued that an excess of information can be a deterrent for patients, as it may lead to difficulties in ensuring valid consent and hinder access to potentially valuable investigations and treatments [ 4 , 5 ].…”