Dr Sandi Dheensa, A. Lucassen, A. Fenwick, G. Crawford The UK 100,000 genomes project: views, expectations, and experiences of the first patients recruited Dr Sandi Dheensa, A. Lucassen, A. Fenwick, G. Crawford Clinical Ethics and Law, Faculty of Medicine University of Southampton, Southampton, United Kingdom.

100,000 genomes project WGS of National Health Service patients with rare diseases + two family members (trios) Organised and delivered by Genomics England (company set up by UK Dept of Health) Aims to enable new scientific discovery and medical insights kick-start UK genomics industry set up genomic medicine service for NHS Research-practice hybrid

Before giving their blood sample Referral from own Dr Phone-call from co-ordinator Information sheets 2-hour consent discussion

100,000 genomes project My team: Practical Ethics GeCIP What are the ethical and social implications? Investigation of why people participate and their experiences and expectations of the project as a whole Decision-making around additional findings PARTNERSHIP

Method Survey with 95 participants (patients/parents) Longitudinal semi-structured interviews 14 interviews n=9 with mothers of patient n=3 with parents of patient n=2 with adult patients Observations of consent sessions Focus groups with healthcare professionals involved in consent

Overview of findings Trust Altruism Hope Participation Reciprocity?

'Consent' is not informed Overwhelmingly positive experiences but… Poor understanding of genetics/genomics and WGS processes: P3: I asked all the questions I needed to at the time, but it’s pretty vague ..they took blood. The only thing I don’t remember them taking is my DNA (M, aged 61+, undiagnosed muscle disease) Written information was unclear and difficult to understand: P8: I’m quite sure that no-one other than medical people had proofread it... (M, aged 61+, undiagnosed muscle disease) Trad way of thinking of consent is informed and for research that it is voluntary Caroline B mentioned GEL is using broad consent model for Afs but my data shows consent is broad in other respects too People talked bout things skipping a generation People also didn't remember whether they had said yes to AFs or not. Inconsistent terminology

Trust in the health service Mother (P13): There’s so much...some of the bits that if I didn’t fully understand, it wasn’t a case of, 'okay I’m going to go off and read this and understand it', it was more like, 'I’m trusting, I’m handing her over to the experts on this'. (teen daughter, suspected Angelmann) Echoes previous research (‘Genetic Alliance: Genome sequencing: What do patients think?’ 2015) So if not on the grounds of information, why are people participating? Echoes research from Genetic Alliance: n=60: 80% happy for NHS to use their data for research purposes- endorsement from our patient community that they welcome current and future initiatives that put the NHS at the heart of this type of research. In contrast, 38% of respondents said that they were comfortable with private companies using their data for research [altho 100kgp has latter it also has former

Hope (and to a lesser extent, altruism) Many wanted a clinical diagnosis. Others wanted to contribute to 'greater good‘; feelings of solidarity with others Mother (P17): “it can be a very lonely place” (Undiagnosed 17 y.o) But deeper digging--at the root of this was still a hope that there would (ultimately) be clinical benefit for themselves/their family; I: If it won’t help your son, why do you care about helping other children in the future? Mother (P1): It might help my son in the future by understanding his condition better...not a cure but better treatment. So I think it will help my son further down the line [4 y.o son with suspected AHC] Another reasons ppl taking part. Expectation.

Hope (and to a lesser extent, altruism) 76, 6, 11 Resp – is it voluntary if compelled to participate because of resp to fam?

Concerns: what next for results? Mother (P11): I feel a bit in the dark. My fear is, we’re not going to be forgotten about are we? They would be keen to follow it through would they? We’ve had that consent interview, now what? (Daughter with suspected hereditary breast cancer) Worries that diagnosis would not be a ‘happy’ one (biographical disruption: Bury, 1980) Most knowledgeable should give them results: not necessarily person they had best relationship with. How will this work as genomics is mainstreamed? Reciprocity? -Worries about diagnosis being the wrong one… hopes that rather than a diagnosis it’s just the manifestations they know about. -They took part on basis of trust. Important that this trusting relationship continue -Implications wrt mainstreaming

Discussion: summary of findings As per previous research, perception of relationships influenced consent (Kelly et al., 2015 relationships with researchers – here relationship with NHS). Consent isn't informed and perhaps not voluntary Is that a 'bad thing'? Should we question decisions to participate? Or is being informed impossible? Should we rethink consent to take into account values such as trust? This trust warrants something in return: reciprocity promotes transparency, fairness, autonomy (Lunshof et al., 2014) If someone is not worried about risk, does that mean they have not understood them? Does it matter that they are not informed? Is it realistic to assume they can be? This isn't a traditional way of doing medicine so do we need to leave traditional conventions and assumptions behind? Kelly, Susan E., et al. Evaluating the consent preferences of UK research volunteers for genetic and clinical studies."PloS one 10.3 (2015): e0118027; Lunshof, Jeantine E., George M. Church, and Barbara Prainsack. Raw personal data: providing access. Science 343.6169 (2014): 373-374.

Next steps: promoting trust and reciprocity Could an electronic health record help? Others areas of medicine suggest so (e.g. Giardina et al., 2014) NHS first electronic health record ('My Medical Record' ) launched in University Hospitals Southampton What tools can be integrated to improve communication? Interactive apps; patient-HCP messaging; communication plan Giardina, Traber Davis, et al. Patient access to medical records and healthcare outcomes: a systematic review. Journal of the American Medical Informatics Association 21.4 (2014): 737-741.

Acknowledgements Clinical Ethics & Law at Southampton -> ..and other collaborators and colleagues for inspiring discussions University Hospitals Southampton staff for recruitment And all participants.