Is “incidental finding” the best term?: a study of patients’ preferences

There is debate within the genetics community about the optimal term to describe genetic variants unrelated to the test indication, but potentially important for health. Given the lack of consensus and the importance of adopting terminology that promotes effective clinical communication, we sought the opinion of clinical genetics patients

A semiquantitative metric for evaluating clinical actionability of incidental or secondary findings from genome-scale sequencing

As genome-scale sequencing is increasingly applied in clinical scenarios, a wide variety of genomic findings will be discovered as secondary or incidental findings, and there is debate about how they should be handled. The clinical actionability of such findings varies, necessitating standardized frameworks for a priori decision making about their analysis

Which came first: validity or clinical testing? The example of long QT genes

Aim: To investigate the potential relationship between the strength of evidence for a gene-disease association and inclusion of the gene on a targeted, indication-based gene panel test for hereditary long QT syndrome (LQTS) and to explore factors that may influence laboratory decisions about the inclusion or exclusion of genes from these clinical tests.Methods: A comprehensive literature search was performed to quantify existing evidence supporting putative LQTS gene-disease associations. This evidence included the year that the gene was first implicated in LQTS, the total number of published cases of LQTS attributed to the gene, and the presence of published segregation and functional data for the gene. To explore the possible relationship between the published evidence for clinical validity of each gene and availability of clinical genetic testing, semi-structured interviews were conducted with key laboratory stakeholders. Representatives from nine US laboratories offering clinical LQTS gene testing agreed to be interviewed regarding decision-making about when and why genes comprising their clinical LQTS test offerings were added.Results: Genes associated with LQTS before 2006 generally had more reported cases of LQTS and the greatest amount of supporting segregation and functional data prior to being offered as a clinical test. For genes first linked to LQTS after 2006, these trends are less linear and the timeframe between initial report and inclusion on clinical test menus decreased substantially. Advances in technology, lifting of patents, clinician request, and literature searches were cited as the main factors that influence composition of LQTS gene panel tests. Paradoxically, one lab director noted that it may require more evidence to remove a gene than to add a gene to a clinical test panel.Conclusion: Our evaluation of the LQTS genes illustrates the nuanced relationship between published evidence supporting a gene-disease association and availability of clinical testing. Expert assessment of clinical validity of gene-disease associations may help laboratories to determine gene panel content. The ultimate impact of such information on the composition of clinical gene tests as well as their utilization by clinicians and coverage by health insurance policies remains to be seen

Is “incidental finding” the best term?: a study of patients’ preferences

PURPOSE: There is debate within the genetics community about the optimal term to describe genetic variants unrelated to the test indication, but potentially important for health. Given the lack of consensus and the importance of adopting terminology that promotes effective clinical communication, we sought the opinion of clinical genetics patients. METHODS: Surveys and focus groups with two patient populations were conducted. Eighty-eight survey participants were asked to rank four terms according to how well each describes results unrelated to the test indication: incidental findings, secondary findings, additional findings, and ancillary findings. Participants in six focus groups were guided through a free-thought exercise to describe desired attributes of such a term, and then asked to formulate a best term to represent this concept. RESULTS: The term additional findings had the most first choice rankings by survey participants, followed by secondary findings, incidental findings, and ancillary findings. Most focus group participants preferred the term additional findings; they also described reasons why other terms were not optimal. CONCLUSION: Additional findings was preferred as both more neutral and accessible than other terms currently in use. Patient perceptions and comprehension will be framed by the terminology. Thus, patient opinions should be considered by medical genetics professionals

A semiquantitative metric for evaluating clinical actionability of incidental or secondary findings from genome-scale sequencing

PURPOSE: As genome-scale sequencing is increasingly applied in clinical scenarios, a wide variety of genomic findings will be discovered as secondary or incidental findings, and there is debate about how they should be handled. The clinical actionability of such findings varies, necessitating standardized frameworks for a priori decision making about their analysis. Genet Med 18 5, 467–475. METHODS: We established a semiquantitative metric to assess five elements of actionability: severity and likelihood of the disease outcome, efficacy and burden of intervention, and knowledge base, with a total score from 0 to 15. Genet Med 18 5, 467–475. RESULTS: The semiquantitative metric was applied to a list of putative actionable conditions, the list of genes recommended by the American College of Medical Genetics and Genomics (ACMG) for return when deleterious variants are discovered as secondary/incidental findings, and a random sample of 1,000 genes. Scores from the list of putative actionable conditions (median = 12) and the ACMG list (median = 11) were both statistically different than the randomly selected genes (median = 7) (P < 0.0001, two-tailed Mann-Whitney test). Genet Med 18 5, 467–475. CONCLUSION: Gene–disease pairs having a score of 11 or higher represent the top quintile of actionability. The semiquantitative metric effectively assesses clinical actionability, promotes transparency, and may facilitate assessments of clinical actionability by various groups and in diverse contexts. Genet Med 18 5, 467–475