retha britz copyright 2013 all rights reserved for this presentation 1 background of bioethics &...
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Retha Britz Copyright 2013 All rights reserved for this presentation1
Background of bioethics & history of research
guidelines
Retha Britz
Nuremburg Code (1947)
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:
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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
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
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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)
World Medical Association published DoH DoH superseded the Nuremburg Code DoH objective: Interests of science and
society do not take precedence over well-being of research pts
Revised 8 times (latest version is 2008) 2008 version currently under revision [2014]
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Declaration of Helsinki (2008)
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
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Declaration of Helsinki (2008) (continue)
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
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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)
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
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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
Study was revealed in the New York Times
on 26 July 1972
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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)
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
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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”
SA GCP Glossary p.89
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Ethics in Health Research: Principles, Structures and Processes (2004)
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
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Guiding Principles as per “Blue Book”
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
Publication of results Conflict of interest Safety monitoring Multi-centre studies Standard of care Placebo-controlled studies Ethical review Distributive justice
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Ethics in Health Research: Principles, Structures and Processes (2004) (continue)
Section 4: Ethics Committees Composition and appointment of members Procedures Monitoring Suspension/discontinuation of research Reports to the NHREC etc.
Section 5: Research requiring additional attention
Minors Vulnerable communities Prisoners etc.19
SA GCP (2006)
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
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“”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 efficacy.” ICH GCP 1.12, p.3
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CIOMS Guidelines (1982)
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
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Other useful guidance documents
International Review Board (IRB) Guidebook. Office for the Protection from Research Risks – National Institute of Health, USA, 1993
World Health Organisation 2000. Operational Guidelines for Ethics Committees that Review Biomedical Research. Geneva
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Animal Research
MRC Guideline Book 3: Use of animals in research and training (2004) prescribes: 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
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Animal Research (continue)
Replacement: of sentient animals with non-sentient research models or systems
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
Refinement: of animal sourcing to minimise or remove physical or psychological distress
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References
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.)
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.)
SCHÜKLENK, U. 2005. Module one: introduction to research ethics. Developing world bioethics, 5(1):1-13.
WORLD MEDICAL ASSOCIATION. 2008. Declaration of Helsinki. (59 th WMA General Assembly, Seoul, October.) http://www.wma.net/e/ethicxsunit/helsinki.htm Date of access: 21 May 2010.