Criteria for reporting incidental findings in clinical exome sequencing – a focus group study on professional practices and perspectives in Belgian genetic centres

Abstract

Background: Incidental and secondary findings (IFs and SFs) are subject to ongoing discussion as potential consequences of clinical exome sequencing (ES). International policy documents vary on the reporting of these findings. Discussion points include the practice of unintentionally identified IFs versus deliberately pursued SFs, patient opt-out possibilities and the spectrum of reportable findings. The heterogeneity of advice permits a nonstandardised disclosure but research is lacking on actual reporting practices. Therefore, this study assessed national reporting practices for IFs and SFs in clinical ES and the underlying professional perspectives. Methods: A qualitative focus group study has been undertaken, including professionals from Belgian centres for medical genetics (CMGs). Data were analysed thematically. Results: All Belgian CMGs participated in this study. Data analysis resulted in six main themes, including one regarding the reporting criteria used for IFs. All CMGs currently use ES-based panel testing. They have limited experience with IFs in clinical ES and are cautious about the pursuit of SFs. Two main reporting criteria for IFs were referred to by all CMGs: the clinical significance of the IF (including pathogenicity and medical actionability) and patient-related factors (including the patient's preference to know and patient characteristics). The consensus over the importance of these criteria contrasted with their challenging interpretation and application. Points of concern included IFs' pathogenicity in non-symptomatic persons, IFs concerning variants of uncertain significance, the requirement and definition of medical actionability and patient opt-out possibilities. Finally, reporting decisions were guided by the interaction between the clinical significance of the IF and patient characteristics. This interaction questions the possible disclosure of findings with context-dependent and personal utility, such as IFs concerning a carrier status. To evaluate the IF's final relevance, a professional and case-by-case deliberation was considered essential. Conclusions: The challenging application of reporting criteria for IFs results in diversified practices and policy perspectives within Belgian CMGs. This echoes international concerns and may have consequences for effective policy recommendations.

Ethical values supporting the disclosure of incidental and secondary findings in clinical genomic testing: a qualitative study

“…Bullock's context-sensitive evaluation of patients' best interest further broadens the concept by stating that the disclosure of medical information should be guided by an evaluation of patients' physical health, their short-and long-term psychological wellbeing and respect for and the facilitation of their (future) autonomy [36]. The delineation of a patient's best interest is related to the debate on IFs' actionability and the question of whether these genomic findings should only enable medical interventions or also personally valuable actions, a topic which we have discussed elsewhere [57].…”

Attitudes among South African university staff and students towards disclosing secondary genetic findings

“…Pathogenicity is an important consideration and is widely debated (Saelaert et al 2019). Disclosure of VUSs might have a significant psychological impact or, as a consequence of unnecessary interventions, medically harmful consequences.…”

“…1. BQ = knowing whether or not they carry a disease mutation can relieve anxiety for some people; BJ = participants have a right to the information; BP = knowing one's propensity for developing particular conditions can help with life planning; BK = it could be life-saving; there's a moral obligation to return lifesaving information; BN = a treatable disorder might be identified; BO = modern reproductive techniques may allow carriers to have children with minimal risk of the specific disorder; BM = concern over legal ramifications over adverse outcomes They could result in unnecessary interventions or harm and a false sense of security (Saelaert et al 2019). This opportunistic screening has been criticised and the American Presidential Commission for the Study of Bioethical Issues (Bioethics Commission) notes how it might entail additional health risks, overwhelm patients with (ambivalent) information and stimulate a trend of medicalisation (Weiner 2014).…”

Incidental diagnosis of mucopolysaccharidosis type I in an infant with chronic intestinal pseudoobstruction by exome sequencing

“…In 2019 Belgian centres for medical genetics [ 17 ] were asked about their practice for reporting criteria for IFs disclosure, which was determined by an interaction between the clinical significance and patient-related factors. International guidelines for the reporting of IFs might be effective only when they are sufficiently detailed but allow reflection for each individual case [ 17 ].…”