To Know or Not to K now: The Importance of Ethics in the Omics Age

1. To Know or Not to Know:The Importance of Ethics in the Omics Age Jón Jóhannes Jónsson, MD, PhD Dept. of Genetics and Molecular Medicine Landspitali - University Hospital Dept. of Biochemistry and Molecular Biology Faculty of Medicine, University of Iceland IFCC World Lab, June 24, 2014

2. Why am I giving this talk? • I am a clinical laboratorian trained in laboratory medicine, clinical biochemistry and medical genetics • Involved in ethical debates • I am not a professional ethicist – and it shows • Accidental ethicist? • No! Ethics is an important and integral part of my profession • Declaration: • No commercial interests in this area • Founder of BioCulea company developing techniques for 2D electrophoresis of nucleic acids

3. Goals • Discuss ethics as a tool for the clinical laboratorian • Case study: Incidental findings in genomics • How to improve skills in ethics

4. Clinical laboratorians are busy people • We have a lot to think about • Our budget is being cut • Please don´t waste our time!

5. Clinical laboratorians need to learn and apply concepts and techniques from many disciplines • Statistics • Quality management • Business • Human resources • I argue that they should also learn ethics

6. Disciplines are defined by concepts and techniques • Clinical chemistry: The application of chemical, molecular and cellular concepts and techniques to the understanding and the evaluation of human health and disease • Ethics is also a discipline defined by concepts and techniques

7. What is ethics about? • Ethics is NOT about NOT doing anything wrong. • It is about making choices • How ought we live our lives? • This is the central question in ethics • There is no final one answer, but decisions still have to be made • Ethics enhances our ability to cope with uncertainty and make decisions  • Making decisions is what clinical laboratory directors are paid to do

8. What tools do we have for decision making? • Beliefs • Science • Common sense • Laws • Professional codes and guidelines • Ethics

9. To use ethics we need to know concepts and techniques • Values: • Degree of importance of something • Rights: • Legal vs. moral rights • Negative and positive rights • Ethical theories - Tools for argument: • Utilitarianism/consequentialism… - maximizing total benefit • Deontology/Kantianism… - the action's adherence to a rule • Virtue theory… - emphasizes the role of one's character • And more…

10. Analysis also requires considering these principles in ethics • Beneficence • Non-maleficence • Autonomy • Justice • Patient autonomy is central

11. How to address ethical dilemmas? • Know the facts • Define ethical dilemmas: • when you have a moral obligation to abide by two different courses of action, but circumstances of the situation only allow for you to choose one of the two courses • Stakeholders….. anyone who is impacted by a decision • Your initial reaction? • Justify your position with arguments • Consider other opinions • Be aware of criticisms and flexible in adjusting your position

12. Sometimes it is difficult to assign priorities to stakeholders

13. At other times it is not!

14. Remember there are always two sides to each story

15. Genetics is Getting More Complex! Krantz ID et al., Amerinan J Med Genet, 2007

16. High throughput sequencing of genomes of humans Sequence of the human genome in a printed form

17. Genome sequencing in practice • Whole exome and even whole genome sequencing is used in research and health care in some settings. • Analysis is more comprehensive than strictly needed to address the clinical problem. • Difficult to assign significance to many findings • Pre- and post-test genetic counseling is time consuming and complex

18. Nothing is new under the sun • Comprehensive analysis generating results unrelated to the indications for testing is not new • Remember mechanical analyzers that delivered panels of tests regardless of what tests were needed clinically • Resurfaces now in Omics technologies on a much bigger scale • The question still the same: Under what circumstances should incidental results be included in laboratory reports and when should they be communicated to the patient?

19. Incidental findings • .. are defined as a findings concerning an individual that have potential health or reproductive importance and arediscovered during testing for an unrelated problem. • Increased susceptibility to a medical condition • Carrier state for a heritable condition • Misatributed paternity

20. Threat or opportunity?

22. Opportunistic screening • Minimum list of incidental findings to report • 54 genes • 24 conditions • Unequivocally pathogenic • Highly penetrant • Medically actionable • Laboratory obligation • Active analysis of NGS data • No opt out

23. What are the ethical dilemmas associated with the ACMG reommendations?

24. Classifying genetic variation is a risky business • Clinical exome sequencing of trios • 4813 gene panel • Filter for de novo mutation • 14 genes • RYR1: c.13910C>T (p.T4637I) • None from the ACMG 54 gene panel • COL6A1: c.1970-3C→A splice mutation • Mutation does not segregate with disease

25. How do people deal with risks?

26. How do peopleassess risk? • People in this context includes patients and health care workers • We use heuristics: • Experience-based techniques for problem solving, learning, and discovery • Rules of thumb • Cognitive shortcuts • Heuristics are used to simplify risk estimates when there is more information available than is possible to absorb and assimilate • Tendency to seek information that confirms a preconceived idea

27. Perception of risk is rarely purely rational • Context-dependent • Imminent risks are more fearful than distant ones • Dramatic or exotic risks perceived as being more dangerous than familiar ones • People tend to exaggerate the risk associated with danger beyond their control. They are less concerned with risk they can manage • No action if risks are not perceived clearly • Gradual accumulation of lifestyle-related risk • The threat of loss has a greater impact than equivalent gain

28. Perception of risk is rarely purely rational (cont.) • Risks of commission (doing something) seem greater than the risk of omission (not doing anything) • Primum non nocere! • Optimism bias: • Overestimate the risk to others, underestimate risk to ourselves: • We have a magical edge over others! • We will live longer and healthier than on average!

29. How good a driver are you? Men Age 18 - 49 Age 50 or older Women • Recent survey of the general adult population in Iceland • Dark red: Excellent • Bright red: Above average

30. On balance • In favor of genome sequencing: • Diagnosis - name and understand the condition • Prognosis - what will happen • Possibility of active therapy • Recurrence risks - will it happen again? • These factors will often be stronger than any possible disadvantage of sequencing

31. Way forward? • Ethics is important • Ethics is becoming more import • What should we do about it?

32. Don´t to be afraid of the future

33. Ethics Task Force of IFCC is conducting a survey • Objective: • To better define educational goals • To identify optimal educational materials for ethics • Recruitment through the IFCC National Representative/Presidents system • Web-based

34. Preliminary results • 80 responders • 39% of the responding programs provide a formal medical ethics course • 31% offer a formal research ethics course • 54% of the training programs; however, reported plans to enhance ethics training • Most interest in using online resources and self-learning • Providing such materials is an important task

35. Thank you Humble humans, in the rain, look at the Statue of Da Vinci in front of La Scala - The interface of art and science