Health-care providers’ perspectives on uncertainty generated by variant forms of newborn screening targets

Pj, Azzopardi; Upshur, Reg; Luca, Stephanie; Venkataramanan,; Bk, Potter; Pk, Chakraborty; Rz, Hayeems

doi:10.1038/s41436-019-0670-3

Cited by 12 publications

(11 citation statements)

References 34 publications

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“…This review exposes concerns about the negative consequences of screening results of uncertain clinical relevance, which overlap with bioethics literature [8,9] and may be shared by HCPs [35].…”

Section: Discussionmentioning

confidence: 99%

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

et al. 2022

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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.

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Section: Discussionmentioning

confidence: 99%

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

et al. 2022

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“…Health care providers in this study also described transferring some of the uncertainty to parents while involving them in the ongoing monitoring of their child for signs and symptoms that may indicate a more serious prognostic outcome than initially suspected. Finally, the importance of being honest about uncertainty rather than seeing it as a weakness was also viewed as being important by health care providers [34]. These studies highlight the difficulties faced by parents trying to understand the NBS outcomes of uncertain long-term significance as well as the importance of health professionals have adequate knowledge and skills to manage these conditions and parental expectations.…”

Section: Dealing With Uncertainty: False Positives and Cf Screen Posimentioning

confidence: 98%

Psychological Impact of NBS for CF

Chudleigh

Chinnery²

2020

IJNS

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Newborn screening for cystic fibrosis has resulted in diagnosis often before symptoms are recognised, leading to benefits including reduced disease severity, decreased burden of care, and lower costs. The psychological impact of this often unsought diagnosis on the parents of seemingly well children is less well understood. The time during which the screening result is communicated to families but before the confirmatory test results are available is recognised as a period of uncertainty and it is this uncertainty that can impact most on parents. Evidence suggests this may be mitigated against by ensuring the time between communication and confirmatory testing is minimized and health professionals involved in communicating positive newborn screening results and diagnostic results for cystic fibrosis to families are knowledgeable and able to provide appropriate reassurance. This is particularly important in the case of false positive results or when the child is given a Cystic Fibrosis Screen Positive, Inconclusive Diagnosis designation. However, to date, there are no formal mechanisms in place to support health professionals undertaking this challenging role, which would enable them to meet the expectations set out in specific guidance.

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“…However, disorders may be missed, some analytes are non-specific, and follow-up testing may be time consuming and complex. 1 , 17 DNA sequencing has the potential to more accurately identify disorders for which MS/MS detection is not optimal and also identify disorders for which there is no appropriate metabolite screen.…”

Section: Pgx and Iems In Current Clinical Practicementioning

confidence: 99%

Opportunities and challenges for the computational interpretation of rare variation in clinically important genes

McInnes

Sharo

Koleske

et al. 2021

The American Journal of Human Genetics

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Summary Genome sequencing is enabling precision medicine—tailoring treatment to the unique constellation of variants in an individual’s genome. The impact of recurrent pathogenic variants is often understood, however there is a long tail of rare genetic variants that are uncharacterized. The problem of uncharacterized rare variation is especially acute when it occurs in genes of known clinical importance with functionally consequential variants and associated mechanisms. Variants of uncertain significance (VUSs) in these genes are discovered at a rate that outpaces current ability to classify them with databases of previous cases, experimental evaluation, and computational predictors. Clinicians are thus left without guidance about the significance of variants that may have actionable consequences. Computational prediction of the impact of rare genetic variation is increasingly becoming an important capability. In this paper, we review the technical and ethical challenges of interpreting the function of rare variants in two settings: inborn errors of metabolism in newborns and pharmacogenomics. We propose a framework for a genomic learning healthcare system with an initial focus on early-onset treatable disease in newborns and actionable pharmacogenomics. We argue that (1) a genomic learning healthcare system must allow for continuous collection and assessment of rare variants, (2) emerging machine learning methods will enable algorithms to predict the clinical impact of rare variants on protein function, and (3) ethical considerations must inform the construction and deployment of all rare-variation triage strategies, particularly with respect to health disparities arising from unbalanced ancestry representation.

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Health-care providers’ perspectives on uncertainty generated by variant forms of newborn screening targets

Cited by 12 publications

References 34 publications

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

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

Psychological Impact of NBS for CF

Opportunities and challenges for the computational interpretation of rare variation in clinically important genes

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