The Continuing Evolution of Ethical Standards for Genomic Sequencing in Clinical Care: Restoring Patient Choice

Abstract

Developing ethical standards for clinical use of large-scale genome and exome sequencing has proven challenging, in part due to the inevitability of incidental or secondary findings. Policy of the American College of Medical Genetics and Genomics (ACMG) has evolved but remains problematic. In 2013, ACMG issued policy recommending mandatory analysis of 56 extra genes whenever sequencing was ordered for any indication, in order to ascertain positive findings in pathogenic and actionable genes. Widespread objection yielded a 2014 amendment allowing patients to opt-out from analysis of the extra genes. In 2015, ACMG published the amended policy, providing that patients could opt out of the full set of extra genes, but not a subset. In 2016, ACMG enlarged the set and indicated planned expansion of the roster of extra genes to include pharmacogenetic findings. ACMG policy does not protect the respect for patient choice that prevails in other domains of clinical medicine, where informed consent allows patients to opt in to desired testing. By creating an expanding domain of genomic testing that will be routinely conducted unless patients reject the entire set of extra tests, ACMG creates an exceptional domain clinical practice that is not supported by ethics or science.

Return of individual genomic research results: are laws and policies keeping step?

“…The popularity of gene panel approaches may raise expectations for researchers to “hunt” for secondary findings. Critics already point out that the routine search for extra genes in clinical contexts is not only expensive, but is also “opportunistic screening” without a sufficient public health basis [22]. With the exception of translational genomics projects seeking to assess the value of using WGS in the clinic, an active search for secondary findings will not be appropriate in research contexts lacking the expertise, infrastructure and resources of clinical organisations.…”

Insights into the Molecular Genetic of Hemophilia A and Hemophilia B: The Relevance of Genetic Testing in Routine Clinical Practice

“…This is a complex issue with many confounding factors, involving ethics and legitimacy. 38 Nowadays, there is a consensus that if these variants are not known to be connected with any phenotype they are of no further concern. If these variants are associated with a clinical phenotype, particularly a severe one, then these incidental findings become relevant and should be reported.…”

Whole-genome sequencing

“…12 If the mutation is in a gene for which there is a known beneficial healthcare intervention, for example, breast cancer surveillance and counselling in a family carrying a BRCA1 mutation, or cardiology review in patients carrying mutations in long QT syndrome genes (ie, medically actionable), and if the patient has consented to receive these results, they would be fed back to them and the appropriate steps would be taken. The ACMG recommendations have been widely debated as they have developed, 13 and there is discussion over the introduction of equivalent UK recommendations. 14 Patients having wholegenome sequencing in the Genomic Medicine Service in England will not have additional findings looked for at first, and the future approach will be guided by the findings from the 100,000 Genomes Project.…”