“Not pathogenic until proven otherwise”: perspectives of UK clinical genomics professionals toward secondary findings in context of a Genomic Medicine Multidisciplinary Team and the 100,000 Genomes Project

Abstract

PurposeApproaches to secondary findings in genome sequencing (GS) are unresolved. In the United Kingdom, GS is now routinely available through the 100,000 Genomes Project, which offers participants feedback of limited secondary findings.MethodsIn Oxford, a Genomic Medicine Multidisciplinary Team (GM-MDT) governs local access to GS, and reviews findings. Semistructured interviews were conducted with 19 GM-MDT members to explore perspectives on secondary findings.ResultsWhile enthusiastic about GS for diagnosing rare disease, members question the rationale for genome screening largely because of lack of evidence for clinical utility and limited justification for use of resources. Members’ views are drawn from diverse experiences; they feel a strong sense of responsibility to act in participants’ best interests. The capacity to return limited secondary findings should be enabled, but members favor a cautious approach that is responsive to accumulating evidence. Informed participant choice is considered critical, yet challenging. Discrimination of variants is considered essential, and requiring of specialist input and consensus. Multiple areas requiring enhanced engagement and education are identified, i.e., for patients, the public, and health-care professionals; at present, mainstreaming of genomics may be premature.ConclusionUK experts believe that evidence to inform policy toward secondary findings is lacking, arguing for caution.

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

“…Knoppers has warned for the "overpromising" of genetic data and, more generally, the pathogenicity, penetrance and expression of variants in asymptomatic persons have been disputed [51]. IFs may vary in reliability and possible use and it should be realised that reporting misinterpreted or uncertain findings might result in unnecessary or harmful follow-ups or interventions [35,37,[52][53][54][55]. Moreover, IFs might cause changes in family, social and professional structures, considerable financial costs, problems regarding insurance or, as already mentioned, emotional harm [35,36].…”

“…For professionals who reject an opt-out possibility, these potential consequences are, per contra, not considered sufficient reasons to outweigh the professional duty of beneficence. If, however, the advantages of reported IFs were surpassed by (possibly underestimated) negative consequences, then the mandatory reporting of IFs invalidates the benefit that paternalism is supposed to provide and violates the professional duty of non-maleficence [55].…”

“…In Belgian CMGs, the current lack of resources and the principle of distributive justice may not only justify the current decision not to actively pursue SFs but also the nationwide use of ES-based panel testing (as both practices limit the amount of analysed genes and hence of required resources). This limitation of possible results (including IFs) is supported by international professionals' questioning of the return and pursuit of IFs and SFs as the most efficient use of limited resources [17,55,59,60]. A filtered analysis minimises (but cannot completely avoid) the chance of IFs and most of the time it is most efficient in terms of diagnostic clinical relevance, it avoids an information overload and it allows clinicians to maximally realise their clinical task [59].…”

Delivering genomic medicine in the United Kingdom National Health Service: a systematic review and narrative synthesis

“…10,[21][22][23][24][25][26] Clinicians reported a lack of guidelines for: pharmacogenomics testing, 21 the collection of family health history, 22 and the disclosure of secondary findings. 23 Lack of guidelines was cited by clinicians as a barrier to genetics service integration, but it could not be determined whether this finding resulted from an actual lack or lack of clinician awareness. 24 Two studies described difficulties translating policies or guidelines into practice.…”

“…Twenty papers describing the preparedness of clinicians 9,14,[21][22][23][24]28,31,[34][35][36][37][38][39][40][41][42][43][44][45][46] found some variations across specialities, but overall clinicians lacked knowledge and/or confidence to implement genomic medicine into practice. 9,21,22,34 Reports described little direct experience with using genetic services 22,35,36 ; feeling unprepared to order tests 21,37 ; interpret and disclose results 9,22,38 and secondary findings 23 ; use pharmacogenomics information 14 ; and respond to patient queries about direct-to-consumer testing. 39 Clinicians' lack of knowledge and awareness could act as a barrier to patients accessing and being referred to genetic services, 31 such as genetic counselling.…”