Transcript Ethics

Background of bioethics &
history of research
guidelines
Retha Britz
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Retha Britz Copyright 2013 All
rights reserved for this
presentation
Nuremburg Code (1947)
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Gruesome experiments conducted by Nazi
doctors in German concentration camps
during WW II
22 doctors found guilty of research
misconduct during the Nuremburg Trial
Nuremburg Code followed as a result
10 principles:
Nuremburg Code (1947) (continue)
 Voluntary IC is essential
 Experiment to be for the
good of society
 Based on animal studies
 Avoid physical & mental
suffering and injury
 Pts to be protected against
injury, disability and death
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 Weigh risks against benefits
 No expectation of death or
disability
 Human experimentation to
be conducted only by
scientifically qualified
individuals
 Pts can terminate
involvement
 Investigators can terminate
the experiment if injury,
disability or death is likely to
occur
Some research still conducted without IC despite
strict requirement for it in the Nuremburg Code
Thalidomide studies in late 1950s to determine
safety and efficacy as a sedative
Also used by pregnant woman
10,000 - 20,000
infants globally with severe teratogenic/neuropathy
side effects
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Declaration of Helsinki (1964)
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World Medical Association published DoH
DoH superseded the Nuremburg Code
DoH objective: Interests of science and
society do not take precedence over wellbeing of research pts
Revised 8 times (latest version is 2008)
2008 version currently under revision [2014]
Declaration of Helsinki (2008)
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Research physician to protect the life, health, dignity, integrity,
right to self-determination, privacy and confidentiality of personal
information of research pts
Research must conform to generally accepted scientific
principles: based on animal experimentation
Appropriate caution exercised in conduct of research that may
harm the environment
Study protocol should be available
Protocol submitted to a research EC before study commence
Research only to be conducted by individuals with appropriate
scientific training and qualifications
Declaration of Helsinki (2008) (continue)
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Research in disadvantaged/vulnerable population is only justified if
research is responsive to health needs and priorities of this
population
benefit from results
Assessment of predictable risks and burdens
benefits
should be foreseeable
Trials to be registered in a publicly accessible database
Research physicians to be confident that risks involved have been
adequately assessed and managed
Important that the objective outweigh the inherent risks and
burdens
Voluntary participation
Protect privacy of research pts and confidentiality of their personal
information
Pts to be adequately informed of all aspects of the trial
Declaration of Helsinki (2008) (continue)
 Consent given for collection, analysis, storage and/or
reuse of identifiable human material or data
 No pts in a dependent relationship with the
investigator or consent under duress
 For incompetent potential pts, consent to be
obtained from the legally authorized representative
 In case the incompetent potential pt can give assent,
the physician should seek assent in addition to
consent of the legally authorized representative.
Dissent should be respected
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Declaration of Helsinki (2008) (continue)
 In case physical or mental incapability is a necessary
characteristic of the research population, IC to be
obtained from a legally authorized representative or
EC IC
asap from pt or representative
 Authors, editors and publishers all have
ethical obligations with regards to the
publication of the research results
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Bioethics (1932-1972)
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 US Public Health Services conducted a syphilis study in
Tuskegee to determine the natural Hx of untreated
syphilis
 400 African-American men with syphilis were pts
 200 without syphilis served as controls
 Pts were recruited without IC
 Pts were told that they are treated for “bad blood” and
was left intentionally untreated
 Transport was provided to and from clinics
 Hot meals were provided at the clinic
Bioethics (1932-1972) (continue)
Free medical care for any disease other than medical
care
 Pts were offered a free funeral policy if they agree to a
post mortem
 Pts not aware that they are in a research study
 1945: Penicillin was found to be effective against
syphilis, but it was never offered/administered
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Study was revealed in the New York Times
on 26 July 1972
 The US Government (President Clinton) formally
apologised to the pts and their families in 1997
 74 of the untreated pts were still living
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Belmont Report (1979)
Autonomy, Beneficence & Justice
based on Principle-based ethics (moral theory)
US follows Belmont Report [acknowledge DoH]
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Appearance of Various Guidelines
 1970s: FDA Guidelines and IND Regulations
 1980s: National Codes - European countries
 1990: Japanese GCP Guidelines
 1991: European GCP Guidelines to improve the
process for developing and registering new medicinal products
USA, Europe and Japan Regulatory Authorities and
Pharmaceutical Companies plus observers from Scandinavia,
Australia, Canada and the WHO held a series of meetings to
develop a set of GCP that would facilitate the universal
acceptance of clinical trial data
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ICH GCP (1996)
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April 1996 was the International Conference on
Harmonization (ICH) of Technical Requirements
for Registration of Pharmaceuticals for Human
use
ICH GCP
Purpose of ICH GCP:
To provide a unified standard to facilitate the
mutual acceptance of clinical data by the
Regulatory Authorities
What is GCP?
“A standard for the design, conduct,
performance, monitoring, auditing,
recording, analyses and reporting of
clinical trials that provides assurance
that the data and reported results are
credible and accurate and that the
rights, integrity and confidentiality of
trial subjects are protected”
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SA GCP Glossary p.89
Ethics in Health Research: Principles,
Structures and Processes (2004)
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Contain the SA National Policy on specific needs in SA
and aims for “enhancing the dignity of South African
citizens”
Intended to be followed by investigators of clinical
research, RECs, administrators, health care
practitioners, policy-makers and community
representatives
The NHA section 72(6)(a) mandates that REC uses
this “blue book”
2004 version currently under revision by the NHREC
Guiding Principles as per “Blue Book”
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Respect and dignity
Relevance of the research
Scientific integrity
Investigator competence
Principal Investigator
responsibility
Informed consent
Privacy and confidentiality
In- and exclusion criteria
Risk and benefits
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Publication of results
Conflict of interest
Safety monitoring
Multi-centre studies
Standard of care
Placebo-controlled studies
Ethical review
Distributive justice
Ethics in Health Research: Principles,
Structures and Processes (2004) (continue)
Section 4: Ethics Committees
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Composition and appointment of members
Procedures
Monitoring
Suspension/discontinuation of research
Reports to the NHREC etc.
Section 5: Research requiring additional
attention
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Minors
Vulnerable communities
Prisoners etc.
SA GCP (2006)
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1st ed. published in 2000
Based on ICH GCP and other guidance documents
such as DoH (2004)
Differences between ICH & SA GCP e.g. section on
Informed Consent
Mainly for researchers conducting clinical trials
No separate guidelines for other researchers
conducting research on/with human
Includes composition of RECs, functioning and
monitoring by RECs
“”Clinical trials" means a systematic study, involving
human subjects that aims to answer specific
questions about the safety or efficacy of or method of
treatment.” NHA, Section 72 (7)
“An investigation in human subjects intended to discover
or verify the clinical, pharmacological, and/or other
pharmadynamic effects of an investigational product,
and or to identify an adverse reaction to an
investigational product and/or to study absorption,
distribution, metabolism and excretion of an IP with
the objective of ascertaining its safety and/or
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efficacy.” ICH GCP 1.12, p.3
CIOMS Guidelines (1982)
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Council for International Organizations or Medical
Sciences Guidelines
Intend to apply DoH in developing countries
Specific attention to large-scale vaccine trials and
medications
Includes section on compensation for injuries related
to research
Shortcomings: Lacks separate section devoted to
risk-benefit ratios
Other useful guidance documents
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International Review Board (IRB) Guidebook. Office
for the Protection from Research Risks – National
Institute of Health, USA, 1993
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World Health Organisation 2000. Operational
Guidelines for Ethics Committees that Review
Biomedical Research. Geneva
Animal Research
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MRC Guideline Book 3: Use of animals in
research and training (2004) prescribes:
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Ethical principles involves
Ethical code of behaviour for researchers,
educators and animal care staff
Human obligation/duties
A legal mandate for animal studies
Ethical review process for animal research
Animal Research (continue)
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Replacement: of sentient animals with non-sentient
research models or systems
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Reduction: of numbers of animals in experiments by
design strategies that facilitates the use of the
smallest number that will allow valid information to
be obtained
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Refinement: of animal sourcing to minimise or
remove physical or psychological distress
References
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DHAI, A., CLEATON-JONES, P. & TSOTSI, N. 2011. The ethics of
research. (In Dhai, A. & McQuoid-Mason, D., eds. Bioethics, human rights and
health law: principles and practice. Claremont: Juta. p. 166-170.)
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MOODLEY, K. 2011. Research ethics and scientific integrity. (In Moodley, K.,
ed. Medical ethics, law and human rights. Pretoria: Van Schaik Publishers. p.
317-337.)
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SCHÜKLENK, U. 2005. Module one: introduction to research ethics.
Developing world bioethics, 5(1):1-13.
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WORLD MEDICAL ASSOCIATION. 2008. Declaration of Helsinki. (59th
WMA General Assembly, Seoul, October.)
http://www.wma.net/e/ethicxsunit/helsinki.htm Date of access: 21 May 2010.