The US Association for Molecular Pathology (AMP) recently published a report on incidental findings in clinical genome sequencing, reviewing next generation sequencing technology in terms of its effect on the laboratory and the patient. The report is a new and interesting addition to the ongoing discussion on how best to integrate genome sequencing into clinical practice; a topic the PHG Foundation has covered previously in its report Realising Genomics in Clinical Practice.
The need for a pathology voice on clinical genomics
The AMP argues that the perspectives of laboratories and of patient autonomy have been mostly overlooked in favour of a discussion about the nature of incidental findings themselves, and in how and when they are provided, especially following the debate caused by the publication of the recommendations of the American College of Medical Genetics and Genomics (ACMG). That debate focused on the recommendation that patients, as a condition of receiving clinical genome sequencing, should be obliged to accept feedback of incidental findings in the form of a set of specific disease-associated genetic variants. Although their position was eventually amended by further comment from the ACMG, a gap remained in the discussion – a gap this new AMP report seeks to fill.
The laboratory perspective
In terms of the laboratory perspective, the AMP argues that reporting specific sets of incidental findings has implications in a number of different areas including consent, analysis, and cost. For example, if a laboratory decides to provide an opt-out for patients, it becomes necessary to modify the analysis to reveal or mask information on whatever specific set of genes are used (such as the 56 recommended for reporting by the ACMG). Changes in recommendations about which genes should be reported would necessitate changes to laboratory workflow.
The AMP also noted that a significant time requirement is added to the laboratory if it needs to report incidental findings for all people undergoing whole-exome sequencing, including family members of the person for whom the sequence was clinically requested (in order to identify the disease-causing variants). Both of these things increase costs, and in the case of the second point, put that laboratory at a competitive disadvantage in comparison to laboratories that perform only targeted analysis of family members.
The patient perspective
For patients, the AMP was of the view that the possibility of receiving incidental findings would not necessarily be desirable for a number of reasons: it may cause more distress than clinical benefit; or it may negatively affect the ability of the recipient to take out certain insurance policies.
Correlations with UK recommendations
The AMP report makes a series of recommendations based on these, and other, observations, a number of which chime with those of the PHG Foundation’s Realising Genomics report. This is especially the case in terms of its recommendations about how to consent a patient for clinical sequencing: the AMP state, for example, that because whole-exome and -genome sequencing are much more complex than single-gene analysis, ‘patients and their families will need to be educated about the possible types of results that could be returned’, and that during the consent process it should be made clear whether the patient or other family members have the option of choosing not to receive incidental results.
This view corresponds with the PHG Foundation’s position on the need for transparency of information during the consent process, and that patients should be informed about the nature and likelihood of incidental findings and be given the opportunity to express their view as to whether incidental findings are disclosed.
The AMP report is a valuable addition to a developing area of policy, but it remains to be seen in what changes actually materialise in the US. The UK is currently consulting on new proposals for genomics laboratory reorganisation that recognise the importance of molecular pathology laboratories in delivery of clinical genome sequencing.
Tom provided regulatory and ethical advice across a broad range of PHG Foundation programmes.More about Tom