Ethics for the Laboratory Physician

Web Teleconference Feb 21 2012JF Magee

Laboratory Medicine/Pediatrics IWK

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

conflict of interest

no conflicts to declare

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

ethics-a history

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

bioethics-a history

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

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

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.

bioethics-a history

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

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

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]

georgetown principles

beneficence an ethical principal which requires

provision of benefits and balancing of benefits and harmNCBHR, 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

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

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

medicine

‘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

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

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

autopsy practice Khong 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 purposesgranted not granted

1999-01 220 26 2001-2 92 21 2002-4 43 110

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%

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).

autopsy practice ethical 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

biological materials ryk 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/

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

biological materials d 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

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

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

biological materials

evidence strong support for biological studies

recommendation initial consent followed by IRB review

if in doubt seek advice NSHEN

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?

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’

Canada National Council on Ethics in Human Research voluntary agreement

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%

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?

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

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

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

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

disclosing adverse eventsPAMAP Model prepare

apologize/express regret

manage the clinical problem

analyze

prevent further harm/eventsapology act of nova scotia 2008

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

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

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

spin

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

questions

who

how

evaluate

evidence that bioethics has improved health outcomes?

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

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