Known unknowns: building an ethics of uncertainty into genomic medicine

Abstract

BackgroundGenomic testing has reached the point where, technically at least, it can be cheaper to undertake panel-, exome- or whole genome testing than it is to sequence a single gene. An attribute of these approaches is that information gleaned will often have uncertain significance. In addition to the challenges this presents for pre-test counseling and informed consent, a further consideration emerges over how - ethically - we should conceive of and respond to this uncertainty. To date, the ethical aspects of uncertainty in genomics have remained under-explored.DiscussionIn this paper, we draft a conceptual and ethical response to the question of how to conceive of and respond to uncertainty in genomic medicine. After introducing the problem, we articulate a concept of ‘genomic uncertainty’. Drawing on this, together with exemplar clinical cases and related empirical literature, we then critique the presumption that uncertainty is always problematic and something to be avoided, or eradicated. We conclude by outlining an ‘ethics of genomic uncertainty’; describing how we might handle uncertainty in genomic medicine. This involves fostering resilience, welfare, autonomy and solidarity.ConclusionsUncertainty will be an inherent aspect of clinical practice in genomics for some time to come. Genomic testing should not be offered with the explicit aim to reduce uncertainty. Rather, uncertainty should be appraised, adapted to and communicated about as part of the process of offering and providing genomic information.

Genetic counselors' perceptions of uncertainty in pretest counseling for genomic sequencing: A qualitative study

“…In contrast, genetic counselors and ordering providers were described by the genetic counselors of this study to associate more uncertainty with genomic sequencing testing, revealing that sources of uncertainty are perceived differently between different loci of uncertainty. This finding builds on previous literature describing patient propensity for unrealistic expectations for genomic sequencing and the need for guided approaches to manage feelings of too much certainty as well as uncertainty (Bernhardt et al, ; Newson et al, ; Tomlinson, et al, ; Wynn, ).…”

“…The critical nature of this process is emphasized by the growing body of literature calling for responsible and prospective reflection of the potential benefits and harms of genomic sequencing in light of its expanding uptake in medicine (Allyse, Sayres, King, Norton, & Cho, ; Johnston et al, ; ACMG, ; Green et al, ). Since genetic counselors are often responsible for pretest genetic counseling, including obtaining informed consent, understanding how genetic counselors appraise uncertainties related to genomic sequencing can provide insight into how they might frame these pretest discussions in order to promote patient‐centered, effective communication, and management of uncertainty in pretest genetic counseling for genomic sequencing (Newson et al, ; Skirton & Bylund, ). Therefore, this study aims to explore genetic counselors' perception of genomic sequencing‐related uncertainties and its perceived impact on their pretest genetic counseling processes.…”

Children and young people's understanding of inherited conditions and their attitudes towards genetic testing: A systematic review

“…The ability to interpret concepts of risk, susceptibility and predisposition requires an understanding of probability that even adults may struggle to grasp . Genetic test results may also require an ability to understand and tolerate uncertainty . Taken together, the complexity of genetic testing opens up the potential for misinterpretation and misunderstandings in children and young people.…”

Epileptic encephalopathies – next generation diagnostics

“…Problem ten powinien być wyraźnie akcentowany już na etapie kierowania pacjenta na badania oraz w procesie poradnictwa genetycznego [17]. Należy także zwrócić uwagę na fakt, że NGS nie jest metodą rekomendowaną w diagnostyce klinicznej do oceny ryzyka chorób wielogenowych/ wieloczynnikowych [15].…”