Ethics for the Laboratory Physician

1. Ethics for the Laboratory Physician Web Teleconference Feb 21 2012 JF Magee Laboratory Medicine/Pediatrics IWK

2. objectives • to provide practical examples of how ethical issues may impact the practice of present day laboratory medicine • to provide an brief overview of • ethics and the growth of bioethics • professional conduct • laboratory medicine specific issues • autopsy practice • utilization of biological materials • medical error • questions of bioethics • ‘spin’ and rules • critical appraisal

3. conflict of interest • no conflicts to declare

4. definitions morals • derived from the Latin word moralitas ‘custom or habit’ • principles, standards or habits with respect to right or wrong in conduct • conformity with generally accepted standard ethics • derived from the Greek word ethikos ‘pertaining to custom and habit’ • a generic term for various ways of understanding and examining moral life • a system or code of morals of a particular person, group, religion or profession etc. • conformity with an elaborated or ideal code of a particular profession terms may be used interchangeably Johnstone MJ. 1999 Bioethics-a nursing perspective 3rd ed profession • an occupation requiring advanced training • self-policing • professional: worthy of the high standards of that profession

5. society benevolence, sincerity, kindliness [Confucius] concept of personhood [Akan Cultures, Africa] religions truth and competence [Christianity] good character [Islam] personal virtue [Judaism] social security [Hinduism] philosophers duty based ethics [Kant] utilitarianism-compare good and bad outcomes [Stuart Mills] social contract to provide for fair process of distribution legal systems theories from all of the above have become entrenched in the more recent field of bioethics medicine ‘the work of healing…in all cultures has been wrapped in moral and religious meanings’ Hippocrates do no harm Ayurvedic medicine strive with all being to heal the sick Islam (Oath of the Muslim Doctor) strive to heal Thomas Percival medical ethics 1803 Florence Nightingale epidemiologist-1854 American Medical Association adapted Percival’s text 1847 ethics-a history

6. 1753 : Lind (HMS Salisbury): concluded that the ‘intervention’ group were more likely to be disease free 1798 : Jenner (cowpox vaccine) his own child and other young children in the neighborhood 1897: Saranelli (yellow fever) : to prove this claim he had injected 5 persons with the isolate US Surgeon General commissioned Walter Reed to identify the cause of yellow fever self experiment on members of the ‘Yellow Fever Board’ only adults would be enrolled written contract payment of $100 if willing to be exposed further $100 if developed illness. bioethics-a history

7. bioethics-a history • 23 Nazi doctors and beaurocrats were tried by the Allies for performing ‘illegal’ experiments on thousands of prisoners • court documents identified 1750 prisoners • high altitude [low pressure] experiments • freezing • malaria • mustard gas • sulphanilaminde • typhus • poison • incendiary bomb • sterilization

8. bioethics-a history • as a result of this the Nuremberg code was enacted • viewed as a ‘document that was needed to restrain a totalitarian regime of unquestionable brutality but was not applicable to the “rest of us” • NYT coverage : • less than 12 articles 1945-47, only the Aug 47 guilty verdict appeared on page 1.

9. 22 studies which he claimed ‘violated basic standards of ethical research with human beings’ children deliberately exposed to hepatitis (Willowbrook, NY) rheumatic fever trial : penicillin withheld from the controls live cancer cells injected into 22 human subjects (Jewish Chronic Disease Hospital, Brooklyn) during bronchoscopy, needle inserted into the left atrium conclusions ‘informed consent’ ‘virtuous investigator’ Beecher, HK. Ethics and clinical research, NEJM, 1966;274:1354-60 Mc Dermott: ‘medicine has given to society the case for its rights in the continuation of clinical investigation’ Annals of In Med,1967;39-42 Eisenberg: ‘the economic and social costs of disease and death eminently justified human experimentation in spite of the inherent limitations of the informed consent ideal’ Science, 1977;1105-10 Lasagna: ‘for the ethical experienced investigator no laws are needed and for the unscrupulous incompetent no laws will help’ Human Aspects of Biomedical investigation,1971;109 bioethics-a history

10. bioethics-a history • study initiated in 1932, Macon County, Alabama • 400 males recruited • not informed of true nature of their condition or of the study, nor were their partners informed • no treatment for syphilis (even after 1940 when penicillin became available) • study ran until 1972 • 74 still alive • perhaps more than 100 had died directly from advanced syphilitic lesions • compensation authorized for survivors in late 70s • formal apology by President Bill Clinton 1997. Reverby SM. Ed ‘Tuskegee’s Truths’. Chapel Hill, University of North Carolina, 2000

11. regulations • The Declaration of Helsinki : Ethical Principles for Medical Research involving Human Subjects [1975] • The Belmont Report : Ethical Principles and Guidelines for the Protection of Human Subjects of Research [1979] • The Common Rule; Title 45 (Public Welfare), Code of Federal Regulations, Part 46 [Protection of Human Subjects) [1991] • The Council for International Organization of Medical Sciences (CIOMS) in collaboration with the World Health Organization (WHO) [2002] • The ICH Harmonized Tripartite Guideline for Good Clinical Practice (ICH-GCP Guideline) [1996] • Tri Council: Ethical Conduct for Research involving Humans [1970-94]

12. georgetown principles • beneficence • an ethical principal which requires • provision of benefits and • balancing of benefits and harm NCBHR, Canada • non-maleficence • not to inflict evil or harm • to prevent evil or harm • to remove evil • respect for the individual • individuals be treated as autonomous • persons with diminished autonomy are entitled to protection • justice • equals to be treated equally • fairness in distribution • provision of what is deserved

13. summary • medical research has not always been conducted in an ethical manner • ‘society’ has expectations • medical research be conducted • benefit will accrue from such medical research • research be conducted in an ‘ethical manner’ • informed consent is viewed as a ‘self evident moral obligation’ • presently numerous sets of ‘rules’ of ethics now exist

14. profession • an occupation, vocation or career where specialized knowledge is applied. • term usually applied to occupations that involve prolonged academic training and a formal qualification. • "professional activity involves systematic knowledge and proficiency.” • usually regulated by • professional bodies • may set examinations of competence • act as a licensing authority for practitioners • enforce adherence to an ethical code of practice • articulate a commitment to service

15. ‘the work of healing has been wrapped in moral and religious meanings’ Hippocrates do no harm Ayurvedic medicine strive with all being to heal the sick. Islam (Oath of the Muslim Doctor) strive to heal treat patient with respect Thomas Percival medical ethics 1803 Florence Nightingale epidemiologist-1854 American Medical Association adapted percival’s text 1847 a commitment to the highest standards of excellence in the practice of medicine a commitment to sustain the interests and welfare of patients a commitment to be responsive to the health needs of society ABIM Project Professionalism medicine

16. CAP • professional duties consistent with current standards • should not associate with other professionals…. who do not practice in a recognized scientific method • should not direct or supervise a laboratory if he/she lacks experience or adequate training • should complete their medical consults in a prompt, accurate and complete form

17. autopsy practice • organ retention • Bristol inquiry [UK] • 1998 BRI Inquiry (Kennedy) • public alarm of death rate in children undergoing cardiac surgery 1996 • parents concern over the death of her 11 month old daughter in 1992 • public inquiry into surgical management of children with complex cardiac disorders • identified a practice of organ retention following autopsy ‘without the realization of parents’ • viewed as standard of care • Alder Hay referred to as an example • Alder Hay [UK] • 1999 Royal Liverpool Children’s Inquiry (Redfern) • public inquiry into practices of the then Professor of Pathology • inappropriate organ retention • identified tissue museum • Halifax • IWK 1995-8 • same anatomic pathologists as Alder Hay • body parts stored in a warehouse • Melbourne [Aus] • 2000 Royal Children’s and Royal Women’s Hospitals • Sydney [Aus] • 2001 Inquiry into matters arising from post-mortem and anatomical examination practices of the institute of Forensic Medicine

18. autopsy practiceKhong TY et al J Peds and Child Health 2006 • autopsy rates falling • 1999-2001 71.7% • 2001-2 61.5% • 2002-3 50.5% • more detailed consent process • less ‘extensive’ procedures • ‘it is likely that they have introduced choice as evidenced by the increase in the number of external examinations in the later years of this study’ • less likely to submit tissue for research and educational purposes granted not granted • 1999-01 220 26 • 2001-2 92 21 • 2002-4 43 110

19. autopsy practiceCartlidge PHT el al. Value and quality of perinatal and infant postmortem exmination:cohort analysis of 400 consecutive deaths BMJ 1996;310:155-158 • all perinatal deaths during a calendar year • assessed ‘quality’ on the basis of the Royal College Guidelines • autopsy rate 53-58% • below standard in 44% of cases • contributory in 17%

20. autopsy practiceMagee JF Drysdale J, ISPD 2010 • a critical appraisal of data obtained from 92 stillbirth autopsies performed at the IWK Health Centre • 2004 consent for ‘full’ autopsy examination in 97% of cases. • 2005 consent in for ‘full’ autopsy examination in 73% of cases. • gross examination of fetus • performed 100% of cases-SNF in 29% of cases • microscopic examination of fetal tissue • performed in 97%-SNF in 16% of cases • cytogenetic studies • performed in 50%-SNF in 15% of cases • radiologic studies • performed in 92% -SNF in 7% of cases • detailed CNS examination • performed in 89%-SNF in 5% of cases • placental examination • performed in 98% of cases-SNF 4% of cases. • average time to produce reports • preliminary 14 days • final reports was 90 days (no CNS) • 170 days (CNS).

21. autopsy practiceethical considerations of the perinatal autopsyTY Khong. J Med Ethics 1996 • consent • who is asked? • who asks? • lack of knowledge in those seeking consent in cases of adult autopsy Chana J et al J Coll Phy Lon 1990 • what constitutes an autopsy • what does consent allow for • who performs the test • what is an acceptable test

22. biological materialsryk ward and the nu’uchalnuth • ryk ward • born UK • grew up NZ • BSc [anthropology, biology, genetics) NZ • Phd [human genetic Ann Arbor] • UBC [faculty position in Medical Genetics] • UBC • 1983 arthritis study-HLA typing • blood samples from the nu’uchalnuth band • later moved to Utah/Oxford (professor of biological anthropology) • kept blood and used them in subsequent studies (migration of aboriginals) • eventually comes to light [1998/9] • nu’uchalnuth • demanded return of samples • demanded codes of behavior • IAH http://www.health-sciences.ubc.ca/iah/ • BC Aboriginal Capacity and Research Development Environment [ACADRE] http://www.health-sciences.ubc.ca/iah/acadre/

23. biological materials • collection and storage of human biological materials has become integral to disease diagnosis and human research • nature of materials is wide ranging • tissue • solid tumor tissue [-70C] • paraffin block • blood samples • NBS blotters • plasma/serum samples • laboratory medical practice requires retention of diagnostic samples-may be viewed as ‘resource’ by research community

24. biological materialsd wendler • systematic review of individuals views regarding consent for research with biological materials • 2483 articles • 31 [views on 33,000 individuals] • 90% want to make their own decision • 80-95%% would donate • 5-10% would not • 6 dealt specifically with residual samples • in 5/6 studies >90% were willing to donate samples for research • in the 6th study 83% were willing to donate

25. biological materialsd wendler • 6 studies • 2 date from the 90s • Start D et al BMJ 1996;313:1366-68 • Hamajima N et al J. Journal Can Res 1998;89:341-6 • 2 published by same group • Lack and Womack • BMJ 2003;327(Aug):262-3 • BMJ 2003;327(Oct):781-2 • ECOG • Malone T et al. JNCI 2002;94:769-771 • 2 consent forms • 89.4% shorter version • 93.7% explicit version • 92.1% for >65 years • 88.7% fro <65 years

26. biological materials • 1990-2000 randomly selected • 1494 donated blood screening for future research on cardiovascular disorders and diabetes mellitus • 2001-attempted re-contact • 1494 • 1409-1342 of whom responded • 93% gave consent for future ‘genetic research’ subject to • IRB approval • 22.3%-to be informed

27. biological materials evidence • strong support for biological studies recommendation • initial consent followed by IRB review if in doubt seek advice • NSHEN

28. biological materials • scenario • 2001 • 13 year old female treated at a pediatric institution with a diagnosis of ARMS (2;13 translocation) • consent obtained for biological study • 2009 • option for new epigenetic study • request to use some of the residual tissue • question • who consented?

29. pediatrics • ‘triadic’ experience • HCW • parents • child • more complex consent process • assent • US National Commission for the Protection of Human Subjects of Biomedical and Behavioral Research’ • the child’s agreement to participate • that assent be obtained from those children whom the local institutional review board [IRB] judged as capable of assenting’ • CanadaNational Council on Ethics in Human Research • voluntary agreement

30. parental viewsFernandez CV, Magee JF Pediatr Blood Cancer 2011 • N=54 (10 with deceased children) • tissue sent anywhere in the world [prefer pediatric aims]-89% • genetic research if it might improve child’s health-76% • research profits used for childhood cancer research-73% • child should confirm consent or reaching majority-98%

31. NBS • consent • screening panel • storage (newborn screening blotters) • how long? • Canada-no uniformity • Quebec-destroy after 1 year unless abnormal • NL, PEI 1-5 years • rest 2-21 years • Germany • all samples destroyed after 3 months • US • Texas-4.5 million samples to be destroyed within 120 days (Dec 23rd 2009) • Minnesota-should all samples be destroyed at 10 years • use for future research?

32. medical errorto err is human IOM • error occurs when there is a ‘failure to complete a planned action as it was intended, or when an incorrect plan is used in an attempt to achieve a given aim’ • an error may be an act of commission or omission • medical error is a significant problem • 44-98,000 hospitalized patients die annually in US • negligence is established only in a court of law • perfection is not the standard

33. medical error • how do mistakes occur? • most are not through negligence • incomplete knowledge base • error in perception/judgment • lapse in attention [fatigue] • system failure • individual competence • not possible to quantify the full magnitude of safety challenge • medication error (wakefield et al, 2001) • mortality rates in intensive care (sexton, 2003) • nurse safety practices (zohar, 2007) • non-optimal practice (mcglynn 2005) • terminology • near miss • adverse event

34. medical errorNakleh RE Arch Pathol Lab Med 2008 • error rate in surgical pathology • 1% • 0.26-1.7% • percentage of errors • specimen identification 33% • defective specimens 4-10% • analytic misinterpretation 25% • defective reports 33-40% • interventions • generic-safety culture • specific • factors that could decrease analytic errors rates • standardization of all procedures • ‘safe’ environment-remove distractions like phones • increased automation • decreased use of inconsistent tools • printing/barcoding versus hand writing • reports • synoptic reporting leads to a 24% increase in ‘complete’ reports

35. medical error • do physicians have an ethical duty to disclose information about medical mistakes to their patients? • CMA Code of Ethics • disclosure • CMPA • disclosure • hospital policy • IWK-disclosure • hospital accreditation body • US-disclosure

36. disclosing adverse eventsPAMAP Model • prepare • apologize/express regret • manage the clinical problem • analyze • prevent further harm/events apology act of nova scotia 2008

37. why don’t doctors apologizeJohn Muir, Dalhousie • difficult to admit fault • consequences are substantial • guilt, shame • lawyers advice • not my fault-that of care team/system

38. why doctors should apologize • why disclose • to prevent further harm • patients due information out of respect • maintains trust • acknowledges commitment • shows understanding • reinforces physician integrity • consistent with trend towards transparency • assures patients that they are not at fault • law suit less likely • non disclosure • involves deception and is a breach physicians fiduciary responsibility to patient • undermines trust in physicians and the medical system

39. spinwillowbrook • beecher • 22 studies which he claimed ‘violated basic standards of ethical research with human beings’ • children deliberately exposed to hepatitis (willowbrook, NY) • study followed a successful campaign to eradicate measles infections in the institution • epidemiologic study of hepatitis • strain was mild [no deaths 1953-57] • infections acquired while at institution by patient contact • initially treated patients with gamma globulin-protected for 39 weeks • hypothesis-’vaccinate’ children with mild strain under gamma globulin cover to develop immunity • no IRB approval untrue • no consent untrue

40. Europe 1945-7 Nuremberg 23 Nazi doctors and beaurocrats were tried by the Allies for performing ‘illegal’ experiments on thousands of prisoners court documents identified 1750 prisoners Asia 1933-56 Japanese Experiments in China Shiro Ishii [Unit 731] captives called ‘maruta’ [logs]-identified only by numbers mainly Chinese US, ANZACS 3000 deaths [possibly more] US granted the researchers granted immunity in return for data USSR 1949-trial at Khabarovsk no western media coverage all 12 defendants returned to Jan by 1956 China trial in 1956 all defendants returned to Japan by1964 spin

41. questions • who • how • evaluate • evidence that bioethics has improved health outcomes?

42. not talked about • Screening • Prenatal • Newborn screening • Molecular genetics • DTC (Direct to consumer) • Access • iKT and utilization • QA and patient safety • Conflict of interest • Priority setting and resource allocation • Cost benefit/utility • Opportunity cost • Organizational ethics

43. resources • bioethics and professionalism • ABIM Project Professionalism • CMA Code of Ethics • advances in bioethics [vol 10] • lost virtue-professional character development in medical education • eds. Kenney N et al Elsevier JAI • cambridge textbook of bioethics • Eds. PA Singer, AM Viens • research • ethical and regulatory aspects of clinical research-readings and commentary • eds. Emanuel Ezekiel et al Johns Hopkins University Press • the oxford textbook of clinical research ethics • eds Emanuel Ezekiel, Christine Grady Robert Crouch et al. • nursing ethics • toward a moral horizon-nursing ethics for leadership and practice. Janet Storch, Patricia Rodney, Rosalie Starzomski. Pearson Prentice Hall Toronto • screening • screening-evidence and practice • A Raffel, JA Muir Gray OUP • ethics and newborn genetic screening • eds Mary Ann Baily, TH Murray • molecular genetics • genetics, health care and public policy. Alison Stuart et al. Cambridge Medicine • evidence based decision making • evidence based healthcare and public health 3rd ed. • JA Muir Gray Churchill Livingstone • evidence based health economics-from effectiveness to efficiency in systematic review. Donaldson and Mugford • using research for effective health promotion. Oliver and Peersman