Negotiating ethical practice when clinical care depends on big data research Dr Sandi Dheensa

1. Negotiating ethical practice when clinical care depends on big data research Dr Sandi Dheensa Research Fellow

2. Outline • I’ll place 100kGP in its broader/future context (NHS genomic medicine service) • Differences between research & clinical care: paradigms, oversight & in practice • The hybrid nature of 100kGP • Faden et al. Ethical framework for when research and clinical care are no longer distinct (based on the learning healthcare system) • Potential for better care in a learning healthcare system • Ways a learning healthcare system might hinder/confuse ethical practice • Directions for future

4. Research oversight: stringent and burdensome

5. Clinical oversight: less so

6. 100kGP as a hybrid offers results, fed back by NHS staff on NHS premises using NHS resources but you can't get a test result without agreeing to participate in big data research so it's a hybrid – part (big data) research, part clinical service...difficult to manage

7. In reality: 100kGP hybrid nature isn't new Boundary between research and clinical care has always been blurred Many NHS trusts and HCPs are research active HCPs might enrol patients in 'therapeutic research' if it's the only way to offer a particular risk-reducing intervention. Debates about genomic researchers' duties of disclosure towards participants. (Biobanks have always been 'hybrid') Motivational drivers distinction not so distinct: practice is a continuous source of data for the production of generalisable knowledge, and this knowledge in turn continuously changes/improves practice Research isn't really more systematic: systematic collection of data is now viewed as good clinical practice and even as obligatory.

8. Faden et al. argue yes “The received view of the research practice distinction leads to overprotection of the rights and interests of patients in some cases and to under-protection in others.” Masks the similarities and over-emphasises the differences Research oversight asks too much of consent (and uses a bureaucratised version) In both settings, oversight focuses on physical harms and not other, ‘data-based’, harms, such as risks to privacy Detracts from what's really important So do we need a new oversight mechanism?

9. Genomics and the learning Healthcare System

10. Genomics as the vehicle for a LHS

11. Genomics as the vehicle for a LHS What will happen to 100kGP biorepository after the project? Will it become an NHS resource? Will it be added to? Assuming the answer is yes...

12. The potential for better care when research and clinical care are combined

13. (1) Promotion of altruism 100kGP: according to GEL enhances altruism. Same could be said of ‘solidarity’ (closely related concept). “they’ve enrolled on the principle that this is altruistic, and they don’t expect any personal benefit. They’re doing it because they want someone else to have a better chance than they did”. (Mark Caulfied)

14. (2) Testing children Childhood testing for adult-onset conditions Parents worry that if child isn’t tested now, they won’t ever be tested Using the genome as a resource over time would be a novel approach in clinical practice might address this issue.

15. (3) Recontacting patients • Reclassification of genetic variants means that previous genetic test results are sometimes re-interpretable • New manifestations are sometimes associated with carrier status/genetic conditions • e.g. Duchenne muscular dystrophy carriers • Patients do not always have the means or understanding to keep abreast of these developments

16. (3) Recontacting patients No policy, legislation or professional consensus exists about whether HCPs have a duty or responsibility to recontact former patients (Carrieri et al., 2016; Otten et al., 2015). However there have been cases about the ‘duty to warn’ or ‘duty to recall’ when it becomes know that a medical device or drug carries a risk or when a HCP with HIV might have infected a patient

17. The ways a integration of research and clinical care might hinder/confuse ethical practice

18. (1) Consent & privacy: who will access & control the data? Pharma: GSK, Roche, and AstraZeneca and others were granted access to 100kGP data as part of an industry trial Tech companies have access if they are providing computing infrastructure, data storage, or genome analysis, etc. Including Illumina Which companies will have access as NHS integrates genomic medicine service?

19. Tensions between individual privacy, common good, potential for benefit to everyone, and (mis)trust in the data controllers WT Ipsos Mori study shows patients and public generally don’t trust pharma and don’t know much about tech companies so assume they are benign

21. (1) Consent & privacy: who will access & control the data? “actors big and small are waking up to the enormous profits that could be made from inexpensive consumer health data.” “If undisclosed algorithmic decision-making starts to incorporate health data, the ability of black-box calculations to accentuate pre-existing biases in society” could greatly increase.

22. (2) Offer of results as undue influence? Altruism misapplied? • As Woods (2016) argues, altruism is sometimes used as rhetoric to rally the public to a common cause and to implicitly call upon their civic duty to endorse the venture. • Detracts from the role of industry and from concerns that participants might have about injustice in the research enterprise (Ursin, 2010; Prainsack and Tutton, 2011) • Distracts from the possibility of a diagnosis

23. (3) Is familial consent desirable, possible, necessary? Familial vs personal: should a person (be able to) ‘donate’ their WGS to a database without first talking to relatives? Dynamic consent: “research participants and their family members could express their own views on research participation of other family members in advance and also in real time as the research progresses...a means for families to share and communicate about the findings.”

24. (4) Is broad consent valid? Or an oxymoron? • Specific and individual-level consent would prohibit research of potential social value. • Broad consent is morally justified in the name of the common good. • And it moves us away from “the sacredness of personal choice” and individualistic autonomy, towards ideas of solidarity and equity. (Donna Dickenson).

25. (4) Is broad consent valid? Or an oxymoron? But how can the potential for benefit to the common good of any research project be assessed? Important to devise approaches to broad consent, but also to recognise limits of consent Provide open, honest, and transparent communication and engagement, for example about the risks and benefits of the activity

27. Empirical work • To be published: • GEL/EAC worries • Patients/family members’ expectations and motivations

28. In sum • Genomics leading us into a new era where research and clinical care is indistinct • New ethical framework needed: careful thinking and regulation merited to ensure patient and public trust is not undermined and benefits that flow from 100kGP and other ventures are shared • To merit trust, data controllers must respect the autonomy of individuals, be transparent, and think carefullyabout privacy, consent and assumptions of altruism

29. Smart, W. (2016), “Target architecture – Outputs from the Interoperability and Population Health Summit”, 21 December. Available at: http://interopen.org/content/Interoperability%20Summit%20-%20Emerging%20Target%20Architecture%20v1-0.pdf. • Carrieri D, Dheensa S, Doheny S, Clarke AJ, Turnpenny PD, Lucassen AM, Kelly SE. Recontacting in clinical practice: an investigation of the views of healthcare professionals and clinical scientists in the United Kingdom. European Journal of Human Genetics. 2017 Jan 4. • Otten E, Plantinga M, Birnie E, Verkerk MA, Lucassen AM, Ranchor AV, Van Langen IM. Is there a duty to recontact in light of new genetic technologies? A systematic review of the literature. Genetics in Medicine. 2014 Dec 11;17(8):668-78. • Ursin LO. Privacy and property in the biobank context. InHEC forum 2010 Sep 1 (Vol. 22, No. 3, pp. 211-224). Springer Netherlands. • Tutton R, Prainsack B. Enterprising or altruistic selves? Making up research subjects in genetics research. Sociology of health & illness. 2011 Nov 1;33(7):1081-95. • Boers SN, Van Delden JJ, Bredenoord AL. Broad consent is consent for governance. The American Journal of Bioethics. 2015 Sep 2;15(9):53-5. • Gymrek M, McGuire AL, Golan D, Halperin E, Erlich Y. Identifying personal genomes by surname inference. Science. 2013 Jan 18;339(6117):321-4.