“Not pathogenic until proven otherwise”: perspectives of UK clinical genomics professionals toward secondary findings in context of a Genomic Medicine Multidisciplinary Team and the 100,000 Genomes Project

Ormondroyd, Elizabeth; Mackley, Michael P.; Blair, Edward; Craft, Judith; Knight, Julian C.; Taylor, Jenny C.; Taylor, John; Watkins, Hugh

doi:10.1038/gim.2017.157

Cited by 70Genomics and Rare DiseasesMedical and Health Sciences ResearchEthics in Clinical Research

“Not pathogenic until proven otherwise”: perspectives of UK clinical genomics professionals toward secondary findings in context of a Genomic Medicine Multidisciplinary Team and the 100,000 Genomes Project

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Ormondroyd, Elizabeth, Mackley, Michael P., Blair, Edward, Craft, Judith, Knight, Julian C., Taylor, Jenny C., Taylor, John, Watkins, Hugh·2018·Genetics in Medicine

DOI 10.1038/gim.2017.157PMC PMC5880578

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Abstract

PurposeApproaches to secondary findings in genome sequencing (GS) are unresolved. In the United Kingdom, GS is now routinely available through the 100,000 Genomes Project, which offers participants feedback of limited secondary findings.MethodsIn Oxford, a Genomic Medicine Multidisciplinary Team (GM-MDT) governs local access to GS, and reviews findings. Semistructured interviews were conducted with 19 GM-MDT members to explore perspectives on secondary findings.ResultsWhile enthusiastic about GS for diagnosing rare disease, members question the rationale for genome screening largely because of lack of evidence for clinical utility and limited justification for use of resources. Members' views are drawn from diverse experiences; they feel a strong sense of responsibility to act in participants' best interests. The capacity to return limited secondary findings should be enabled, but members favor a cautious approach that is responsive to accumulating evidence. Informed participant choice is considered critical, yet challenging. Discrimination of variants is considered essential, and requiring of specialist input and consensus. Multiple areas requiring enhanced engagement and education are identified, i.e., for patients, the public, and health-care professionals; at present, mainstreaming of genomics may be premature.ConclusionUK experts believe that evidence to inform policy toward secondary findings is lacking, arguing for caution.

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Some professionals doubt that all patients will benefit significantly from precision medicine.
“Apart from these positive assessments, studies also demonstrate that some professionals are uncertain about the value of genetic testing [51, 90] and doubt that all patients will benefit significantly from PM [30, 31, 42, 49, 54, 57].”
From Patients’ and professionals’ views related to ethical issues in precision medicine: a mixed research synthesis (2021) · cites this paper as [42]
The Abstract’s Results (page unavailable) report that some professionals questioned genome screening because evidence of clinical utility was lacking. The Results on informed consent also say some thought participants overestimated the yield and value of secondary findings. These concerns support doubt about benefit in that specific setting, but not the broader claim about whether all patients benefit significantly from precision medicine. (LLM, conf=0.85)
Experimental — accuracy not yet measured
Many clinicians and researchers are well aware of the limited or ambiguous evidence for the meaning of test results and possible treatment outcomes and regard the lack of practice guidelines as a barrier for the implementation of tests.
“Many clinicians and researchers are well aware of the limited [27, 30, 31, 35, 42, 79, 84] or ambiguous evidence [32] for the meaning of test results and possible treatment outcomes and regard the lack of practice guidelines as a barrier for the implementation of tests [27, 79].”
From Patients’ and professionals’ views related to ethical issues in precision medicine: a mixed research synthesis (2021) · cites this paper as [42]
The Results (‘Rationale for search for SF in clinical GS’; page unavailable) report that some UK genomics professionals considered the evidence too limited to interpret the implications of secondary findings reliably. The Discussion (page unavailable) also describes uncertainty about their clinical utility. The paper calls for professional guidance, but the passages do not establish that these professionals regarded a lack of practice guidelines as a barrier to implementing tests. (LLM, conf=0.85)
Experimental — accuracy not yet measured
Challenges in obtaining informed consent include complex discussions about risks, the length of documents, the lack of understanding by professionals and the resources required.
“Challenges in obtaining informed consent include complex discussions about risks, the length of documents, the lack of understanding by professionals and the resources required [42].”
From Patients’ and professionals’ views related to ethical issues in precision medicine: a mixed research synthesis (2021) · cites this paper as [42]

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Authors: Ormondroyd, E., Mackley, M. P., Blair, E., Craft, J., Knight, J. C., Taylor, J. C., Taylor, J., & Watkins, H.
Affiliations: National Institute for Health and Care Research (GB)
University of Oxford (GB)
Centre for Human Genetics (GB)
Corresponding author: Ormondroyd, Elizabeth
ORCID: Ormondroyd, Elizabeth
Mackley, Michael P.
Knight, Julian C.
Taylor, Jenny C.
Taylor, John
Watkins, Hugh
Venue: Genetics in Medicine
Publisher: Elsevier BV
Published: 2018-03
Volume: 20
Issue: 3
Pages: 320-328
ISSN: 1098-3600 (ISSN-L)
DOI: 10.1038/gim.2017.157
PMC: PMC5880578
OpenAlex: W2766084477
Cited by: 70
References: 40
Citations by year: 2026: 3 · 2025: 2 · 2024: 3 · 2023: 7 · 2022: 9 · 2021: 22 · 2020: 4 · 2019: 14 · 2018: 6
FWCI: 4.36
Type: journal article
Language: en
Open access: hybrid
doi.org
Licence: cc-by
www.elsevier.com/tdm/userlicense/1.0/ (tdm)
www.elsevier.com/legal/tdmrep-license (tdm)
creativecommons.org/licenses/by/4.0/ (vor, 1364 d)
Locations: Genetics in Medicine (publishedVersion, cc-by)
Europe PMC (PubMed Central) (publishedVersion, cc-by)
PubMed Central (publishedVersion, cc-by)
PubMed (publishedVersion)
Funders: Wellcome Trust (204969/Z/16/Z)
National Institute for Health and Care Research (NF-SI-0513-10087)
Versus Arthritis (20773)
NIHR Oxford Biomedical Research Centre
Topics: Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genomics and Rare Diseases
Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Medical and Health Sciences Research
Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Ethics in Clinical Research
Keywords: secondary findings, genome sequencing, 100,000 Genomes Project, rare disease diagnosis, genome scan, informed consent, variant interpretation, genetic discrimination, professional perspectives, healthcare resource allocation
MeSH terms: Female, Genetic Testing, Genetics, Medical, United Kingdom, Health Personnel, Humans, Male, Surveys and Questionnaires, Genetic Predisposition to Disease, Genomics, Disclosure, Incidental Findings, Rare Diseases, Genetic Association Studies

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“Not pathogenic until proven otherwise”: perspectives of UK clinical genomics professionals toward secondary findings in context of a Genomic Medicine Multidisciplinary Team and the 100,000 Genomes Project

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