This document aims to address five specific issues that have provoked concerns among commentators: patient autonomy, children, clinical laboratory issues, communication of results, and prediction of disease risk.
The ACMG's approach to patient autonomy drew the heaviest criticism from PHG Foundation experts (see previous commentary), who found the recommendation that patients should be obliged to accept the feedback of incidental findings in the form of a set of specific disease-associated genetic variants as a condition of clinical genome sequencing ethically unacceptable. Whilst firmly acknowledging the potential clinical value of offering simultaneous analysis for the presence of these selected variants, the PHG Foundation concluded that failure to offer patients the ability to opt out of such testing or feedback of results was: 'a coercive strategy that should have no place in the modern practice of medicine'.
The ACMG has now released further information reiterating that the selected variants they specified are such that the identification of their presence 'conveys a near certainty of an adverse yet potentially preventable medical outcome' and on this basis, failure to communicate the results would be unethical. They also emphasise that the clinician who ordered the sequencing will receive the results so that they can 'participate in a shared decision-making process regarding the return of results' directly with their patient.
This 'clarification', however, fails to acknowledge that such results are not genuinely 'incidental' but require explicit interrogation and analysis of other areas of the genome. It makes no mention of the lower predictive value of variants found in the context of screening (where the prior prevalence of the relevant disease is lower than would be in the clinical context). Nor does it address directly the question of why competent adult patients are denied the opportunity to consent to, or allowed to opt-out from, what is in effect an example of 'opportunistic screening' or 'case finding' rather than part of the investigation of the presenting clinical problem.
Our stance is that, even accepting that such screening is beneficial to the patient, the recommendations of the ACMG are contrary to the vast majority of ethical and legal opinion about the fundamental importance of patient autonomy and the need for consent. We also accept that if in the course of clinical investigation a physician comes across a truly incidental but significant finding it would be right to communicate this to the patient, but we are of the view that the search for specific secondary findings cannot be called incidental in the same sense. We also question the idea that the recommendations can be seen as participation in shared decision-making between clinician and patient if the latter's options are limited to taking the medically indicated genome sequencing plus obligatory testing for other significant variants, or leaving it.
The fundamental issue is not whether the ACMG should or should not recommend the offer of such testing. It is that the patient is obliged to accept the offer that concerns us, and for which no justification is given.
Philippa leads our communications and knowledge management activities, including dissemination of the PHG Foundation’s activities and outputs.More about Philippa