A lecture presented by Dr. Ghaiath Hussein in University of Khartoum for the students of the MSc programme in Genetics/Molecular Biology.
Session 1 (Introduction): Definition of ethics, bioethics and medical ethics.
What is an ethical issue?
International approaches to medical ethics
Islamic approaches to medical ethics
Ethical implication of Human genome project,
International ethical & legal issues connected with human genome diversity research,
Genetic studies of ethnic races.
This ppt have a detailed source about the Biosafety issues in Biotechnology and their implements over by the government. It have a topics about the issues in antibiotic resistance gene , GMO crops etc.
Basics of BioSafety
This lesson will define and present information on
methods used to provide biosafety in facilities
where potentially infectious agents are used.
These include:
Containment
Biological safety cabinets
Personal protection equipment
The facility as barrier
Secondary barriers
Ethical implication of Human genome project,
International ethical & legal issues connected with human genome diversity research,
Genetic studies of ethnic races.
This ppt have a detailed source about the Biosafety issues in Biotechnology and their implements over by the government. It have a topics about the issues in antibiotic resistance gene , GMO crops etc.
Basics of BioSafety
This lesson will define and present information on
methods used to provide biosafety in facilities
where potentially infectious agents are used.
These include:
Containment
Biological safety cabinets
Personal protection equipment
The facility as barrier
Secondary barriers
Biotechnology in Food and Agriculture; the Biosafety Issues [Tarek Alfalah, U...UNESCO Venice Office
Workshop on Higher Education and Professional Responsibility in CBRN Applied Sciences and Technology across the Sub-Mediterranean Region
3-4 April 2012. Palazzo Zorzi, Venice
Session 4. Future Directions - Higher Education and Responsible Science
Ethical issues in biotechnology and related areas.
For soft copy of this document please feel free to contact us on info@biotechsupportbase.com or snjogdand@gmail.com
Biotechnology in Food and Agriculture; the Biosafety Issues [Tarek Alfalah, U...UNESCO Venice Office
Workshop on Higher Education and Professional Responsibility in CBRN Applied Sciences and Technology across the Sub-Mediterranean Region
3-4 April 2012. Palazzo Zorzi, Venice
Session 4. Future Directions - Higher Education and Responsible Science
Ethical issues in biotechnology and related areas.
For soft copy of this document please feel free to contact us on info@biotechsupportbase.com or snjogdand@gmail.com
Growth rates for organic packaged food have struggled to return to their pre-recession heights and there are those in the industry that in are search of another label that represents natural, healthy and sustainable food. Could national or even regional branding replace the need for an organic label? We look at what the term organic means for consumers around the world and what its potential replacements are.
Innovation and the Earned Brand is Edelman's global survey of consumer attitudes toward brand innovation. The online survey was fielded between April and May 2015 across 10,000 consumers in 10 countries, with additional qualitative research among millennials in 5 countries.
EMPHNET-PHE Course: Module seven ethical issues in public health research& in...Dr Ghaiath Hussein
This is a series of presentations I gave in the Eastern Mediterranean Public Health Network (EMPHNET)'s Public Health Ethics (PHE) that was held in Amman in June 2014.
This presentation outlines the ethical issues in research, especially the international research in low-middle income countries
This is a presentation I gave to the Research Coordinators in the Federal Ministry of Health, Sudan (04.03.2015).
It included the following topics:
• Overview on the Knowledge Management Cycle and how research fits in it
• Brief historical background on research ethics
• What makes research ethical?
• Definition and examples of scientific misconduct
• How to make your research ethical and avoid scientific misconduct?
Ethical Concerns Regarding Research on Human SubjectsClinosolIndia
Research involving human subjects raises important ethical concerns that need to be carefully addressed to protect the rights, welfare, and dignity of participants. Here are some key ethical concerns regarding research on human subjects:
Informed Consent: Obtaining informed consent is a fundamental ethical principle in research. Participants must be fully informed about the purpose, risks, potential benefits, procedures, and alternatives of the study before voluntarily agreeing to participate. Informed consent should be obtained in a language and format that participants can understand, and they should have the freedom to withdraw from the study at any time without repercussions.
Beneficence and Non-maleficence: Researchers have an ethical obligation to maximize potential benefits and minimize risks and harms to participants. The potential benefits of the research should outweigh any foreseeable risks. Researchers should ensure participant safety, monitor adverse events, and take appropriate measures to mitigate risks.
Privacy and Confidentiality: Participants' privacy must be protected throughout the research process. Personal identifiable information should be kept confidential and handled securely. Data should be anonymized or de-identified whenever possible to ensure participant confidentiality. Researchers should obtain informed consent specifically for data sharing and ensure compliance with applicable data protection regulations.
Protection of Vulnerable Populations: Special protections are required for individuals who may be vulnerable due to age, cognitive impairments, illness, or other factors. Examples include children, pregnant women, prisoners, individuals with disabilities, and economically or socially disadvantaged groups. Additional safeguards should be in place to minimize potential exploitation and ensure their rights and welfare are protected.
Research Ethics Review: Independent research ethics review committees, often called Institutional Review Boards (IRBs) or Ethics Committees (ECs), play a crucial role in evaluating the ethical aspects of research protocols. They assess the study's scientific merit, participant protection measures, and compliance with ethical guidelines and regulations. Research should not proceed without receiving ethical approval from these committees.
Transparency and Integrity: Researchers have an ethical responsibility to conduct research with integrity and honesty. They should accurately report the methodology, results, and limitations of the study, avoiding any fabrication, falsification, or plagiarism. Transparency promotes trust in the research process and allows for scrutiny, replication, and further advancement of knowledge.
Equity and Justice: Research should be conducted in a fair and equitable manner, avoiding any unjust discrimination or exploitation.
نظرية التطور عند المسلمين (بروفيسور محمد علي البار
ويقدم فيها سردا تاريخيا لنظريات نشأة الخلق وخلق آدم وكيف ان نظرية التطور هي نظرية علمية وليس دينية لكن تم استغلالها لمحاربة الكنيسة
Ethical considerations in research during armed conflicts.pptxDr Ghaiath Hussein
My talk @AUBMC Salim El-Hoss Bioethics Webinar Series. In this webinar, we have discussed the following points:
1- How armed conflicts affect the planning and conduct of research?
2- What is ethically unique about research during armed conflicts?
3- How did my doctoral project approach these ethical issues both at the normative and the empirical levels?
4- What are the lessons learned from the conflicts in the middle east (Sudan, Syria, Yemen, etc.) and how do they differ from the situation in Ukraine?
Acknowledgement: This talk is based on my doctoral thesis (http://etheses.bham.ac.uk/8580/), which was fully funded by Wellcome Trust, UK.
Research or Not Research? This Is Not the Question for Public Health Emergencies
November 17, 2021 @ 4:00 pm - 5:00 pm EST
Speaker:
Ghaiath Hussein, Assistant Professor, Medical Ethics and Law, Trinity College Dublin, Ireland
About this Seminar:
Public health emergencies, whether natural or man-made, local or global, in peacetime or during armed conflicts are always associated with the need to collect data (and sometimes biological samples) about and from those affected by these emergencies. One of the central questions in the relevant literature is whether the activities that involve the collection of data and/or biological samples are considered ‘research’, with the subsequent endeavour to define what ‘research’ is and whether they should be submitted for ethical approval or not. In this seminar, I will argue that this is not the central question when it comes to research/public health/humanitarian ethics. Using the findings of a systematic review on the research conducted in Darfur and findings from a qualitative project that aimed at defining what constitutes ‘research’ in public health emergencies I will, alternatively, present what I refer to as the ‘ethical characterization’ of these research-like activities and how they can be ethically guided.
Richard's aventures in two entangled wonderlandsRichard Gill
Since the loophole-free Bell experiments of 2020 and the Nobel prizes in physics of 2022, critics of Bell's work have retreated to the fortress of super-determinism. Now, super-determinism is a derogatory word - it just means "determinism". Palmer, Hance and Hossenfelder argue that quantum mechanics and determinism are not incompatible, using a sophisticated mathematical construction based on a subtle thinning of allowed states and measurements in quantum mechanics, such that what is left appears to make Bell's argument fail, without altering the empirical predictions of quantum mechanics. I think however that it is a smoke screen, and the slogan "lost in math" comes to my mind. I will discuss some other recent disproofs of Bell's theorem using the language of causality based on causal graphs. Causal thinking is also central to law and justice. I will mention surprising connections to my work on serial killer nurse cases, in particular the Dutch case of Lucia de Berk and the current UK case of Lucy Letby.
Deep Behavioral Phenotyping in Systems Neuroscience for Functional Atlasing a...Ana Luísa Pinho
Functional Magnetic Resonance Imaging (fMRI) provides means to characterize brain activations in response to behavior. However, cognitive neuroscience has been limited to group-level effects referring to the performance of specific tasks. To obtain the functional profile of elementary cognitive mechanisms, the combination of brain responses to many tasks is required. Yet, to date, both structural atlases and parcellation-based activations do not fully account for cognitive function and still present several limitations. Further, they do not adapt overall to individual characteristics. In this talk, I will give an account of deep-behavioral phenotyping strategies, namely data-driven methods in large task-fMRI datasets, to optimize functional brain-data collection and improve inference of effects-of-interest related to mental processes. Key to this approach is the employment of fast multi-functional paradigms rich on features that can be well parametrized and, consequently, facilitate the creation of psycho-physiological constructs to be modelled with imaging data. Particular emphasis will be given to music stimuli when studying high-order cognitive mechanisms, due to their ecological nature and quality to enable complex behavior compounded by discrete entities. I will also discuss how deep-behavioral phenotyping and individualized models applied to neuroimaging data can better account for the subject-specific organization of domain-general cognitive systems in the human brain. Finally, the accumulation of functional brain signatures brings the possibility to clarify relationships among tasks and create a univocal link between brain systems and mental functions through: (1) the development of ontologies proposing an organization of cognitive processes; and (2) brain-network taxonomies describing functional specialization. To this end, tools to improve commensurability in cognitive science are necessary, such as public repositories, ontology-based platforms and automated meta-analysis tools. I will thus discuss some brain-atlasing resources currently under development, and their applicability in cognitive as well as clinical neuroscience.
(May 29th, 2024) Advancements in Intravital Microscopy- Insights for Preclini...Scintica Instrumentation
Intravital microscopy (IVM) is a powerful tool utilized to study cellular behavior over time and space in vivo. Much of our understanding of cell biology has been accomplished using various in vitro and ex vivo methods; however, these studies do not necessarily reflect the natural dynamics of biological processes. Unlike traditional cell culture or fixed tissue imaging, IVM allows for the ultra-fast high-resolution imaging of cellular processes over time and space and were studied in its natural environment. Real-time visualization of biological processes in the context of an intact organism helps maintain physiological relevance and provide insights into the progression of disease, response to treatments or developmental processes.
In this webinar we give an overview of advanced applications of the IVM system in preclinical research. IVIM technology is a provider of all-in-one intravital microscopy systems and solutions optimized for in vivo imaging of live animal models at sub-micron resolution. The system’s unique features and user-friendly software enables researchers to probe fast dynamic biological processes such as immune cell tracking, cell-cell interaction as well as vascularization and tumor metastasis with exceptional detail. This webinar will also give an overview of IVM being utilized in drug development, offering a view into the intricate interaction between drugs/nanoparticles and tissues in vivo and allows for the evaluation of therapeutic intervention in a variety of tissues and organs. This interdisciplinary collaboration continues to drive the advancements of novel therapeutic strategies.
A brief information about the SCOP protein database used in bioinformatics.
The Structural Classification of Proteins (SCOP) database is a comprehensive and authoritative resource for the structural and evolutionary relationships of proteins. It provides a detailed and curated classification of protein structures, grouping them into families, superfamilies, and folds based on their structural and sequence similarities.
Introduction:
RNA interference (RNAi) or Post-Transcriptional Gene Silencing (PTGS) is an important biological process for modulating eukaryotic gene expression.
It is highly conserved process of posttranscriptional gene silencing by which double stranded RNA (dsRNA) causes sequence-specific degradation of mRNA sequences.
dsRNA-induced gene silencing (RNAi) is reported in a wide range of eukaryotes ranging from worms, insects, mammals and plants.
This process mediates resistance to both endogenous parasitic and exogenous pathogenic nucleic acids, and regulates the expression of protein-coding genes.
What are small ncRNAs?
micro RNA (miRNA)
short interfering RNA (siRNA)
Properties of small non-coding RNA:
Involved in silencing mRNA transcripts.
Called “small” because they are usually only about 21-24 nucleotides long.
Synthesized by first cutting up longer precursor sequences (like the 61nt one that Lee discovered).
Silence an mRNA by base pairing with some sequence on the mRNA.
Discovery of siRNA?
The first small RNA:
In 1993 Rosalind Lee (Victor Ambros lab) was studying a non- coding gene in C. elegans, lin-4, that was involved in silencing of another gene, lin-14, at the appropriate time in the
development of the worm C. elegans.
Two small transcripts of lin-4 (22nt and 61nt) were found to be complementary to a sequence in the 3' UTR of lin-14.
Because lin-4 encoded no protein, she deduced that it must be these transcripts that are causing the silencing by RNA-RNA interactions.
Types of RNAi ( non coding RNA)
MiRNA
Length (23-25 nt)
Trans acting
Binds with target MRNA in mismatch
Translation inhibition
Si RNA
Length 21 nt.
Cis acting
Bind with target Mrna in perfect complementary sequence
Piwi-RNA
Length ; 25 to 36 nt.
Expressed in Germ Cells
Regulates trnasposomes activity
MECHANISM OF RNAI:
First the double-stranded RNA teams up with a protein complex named Dicer, which cuts the long RNA into short pieces.
Then another protein complex called RISC (RNA-induced silencing complex) discards one of the two RNA strands.
The RISC-docked, single-stranded RNA then pairs with the homologous mRNA and destroys it.
THE RISC COMPLEX:
RISC is large(>500kD) RNA multi- protein Binding complex which triggers MRNA degradation in response to MRNA
Unwinding of double stranded Si RNA by ATP independent Helicase
Active component of RISC is Ago proteins( ENDONUCLEASE) which cleave target MRNA.
DICER: endonuclease (RNase Family III)
Argonaute: Central Component of the RNA-Induced Silencing Complex (RISC)
One strand of the dsRNA produced by Dicer is retained in the RISC complex in association with Argonaute
ARGONAUTE PROTEIN :
1.PAZ(PIWI/Argonaute/ Zwille)- Recognition of target MRNA
2.PIWI (p-element induced wimpy Testis)- breaks Phosphodiester bond of mRNA.)RNAse H activity.
MiRNA:
The Double-stranded RNAs are naturally produced in eukaryotic cells during development, and they have a key role in regulating gene expression .
Seminar of U.V. Spectroscopy by SAMIR PANDASAMIR PANDA
Spectroscopy is a branch of science dealing the study of interaction of electromagnetic radiation with matter.
Ultraviolet-visible spectroscopy refers to absorption spectroscopy or reflect spectroscopy in the UV-VIS spectral region.
Ultraviolet-visible spectroscopy is an analytical method that can measure the amount of light received by the analyte.
Earliest Galaxies in the JADES Origins Field: Luminosity Function and Cosmic ...Sérgio Sacani
We characterize the earliest galaxy population in the JADES Origins Field (JOF), the deepest
imaging field observed with JWST. We make use of the ancillary Hubble optical images (5 filters
spanning 0.4−0.9µm) and novel JWST images with 14 filters spanning 0.8−5µm, including 7 mediumband filters, and reaching total exposure times of up to 46 hours per filter. We combine all our data
at > 2.3µm to construct an ultradeep image, reaching as deep as ≈ 31.4 AB mag in the stack and
30.3-31.0 AB mag (5σ, r = 0.1” circular aperture) in individual filters. We measure photometric
redshifts and use robust selection criteria to identify a sample of eight galaxy candidates at redshifts
z = 11.5 − 15. These objects show compact half-light radii of R1/2 ∼ 50 − 200pc, stellar masses of
M⋆ ∼ 107−108M⊙, and star-formation rates of SFR ∼ 0.1−1 M⊙ yr−1
. Our search finds no candidates
at 15 < z < 20, placing upper limits at these redshifts. We develop a forward modeling approach to
infer the properties of the evolving luminosity function without binning in redshift or luminosity that
marginalizes over the photometric redshift uncertainty of our candidate galaxies and incorporates the
impact of non-detections. We find a z = 12 luminosity function in good agreement with prior results,
and that the luminosity function normalization and UV luminosity density decline by a factor of ∼ 2.5
from z = 12 to z = 14. We discuss the possible implications of our results in the context of theoretical
models for evolution of the dark matter halo mass function.
Earliest Galaxies in the JADES Origins Field: Luminosity Function and Cosmic ...
Ethical considerations in molecular & biotechnology research
1. PRESENTED FOR UNIVERSITY OF KHARTOUM
MSC PROGRAMME IN GENETICS/MOLECULAR
BIOLOGY
30/04/2014
Presented by:
Ghaiath Hussein, MBBS, MHSc. (Bioethics)
Doctoral Researcher, Uni. Of Birmingham, UK
ghaiathme@gmail.com
2. Outline of today’s session
Introduction: Research and Knowledge Management
Cycle (KMC)
Historical background of research ethics
What makes research ethical?
Examples of ethical issues in biotechnological and
molecular research
How to proceed with our research ethically?
3. What is Research?
“Research” is defined as an undertaking intended to
extend knowledge through a disciplined inquiry or
systematic investigation.
Systematic methodological scientific approach for basic
facts around a certain problem in order to find solutions
based on these facts.
Research on Humans:
The systematic undertaking of activities that involve the
collection of human personal data, measurements, and/or
biological samples for purposes that are not related to
clinical management of a health condition
6. “Good” research: Good Science & Good
Ethics
“Good” Evidence: near-top to
hierarchy of Evidence
Evidence-Based Healthcare:
Better practice that is based on best evidence
Better health status
Better Ethics is Better Health
7. What Makes a Good Research?
Good
science
Good
Ethics
•Problem selection
•SMART objectives
•Proper methodology
•Proper analysis
•Fair subject selection
•Favorable Risk-Benefit Ratio
•Independent Review
•Informed Consent
8. Criteria of “Good” Science Research
Systematic: The research developed, implemented
and reported in a systematic manner.
Methodolic: Adopt & use skillfully the research
methods, materials ,approaches in order to ensure
reliability of the results & findings.
Scientific: The research should be scientifically
sound through utilizing scientific approaches , tools
and techniques.
9. Criteria for Good Ethics:
What Makes Research Ethical?
1. Social or Scientific Value
2. Scientific Validity
3. Fair Subject Selection
4. Favorable Risk-Benefit Ratio
5. Independent Review
6. Informed Consent
7. Respect for the potential and enrolled
subjects
10. What’s Research Ethics?
It is the field of ethics that systematically analyze the ethical
and legal questions raised by research involving human
subjects.
Its main focus is to ensure that the study participants are
protected and, ultimately,
that clinical research is conducted in a way that
serves the needs of such participants and of
society as a whole.
It works when and only when it is applied before the
research is conducted
11.
12. History of Research Ethics
Pre-World War II
Research standards left up to the discretion of the individual
researcher
World War II
Experiments conducted on inmates of Nazi concentration
camps
1945-1949 - Trials in Nuremberg, Germany– physicians
convicted of crimes against humanity
13. Year Benchmark
2013 WMA updates DOH (Brazil)
2010 TCPS updated
2008 WMA updates DOH (Seoul)
2004 WMA updates DOH (Tokyo)
2002 WMA updates DOH (Washington) CIOMS Guidelines updated
2000 WMA updates DOH (Edinburgh)
1998 Tri-Council Policy Statement (TCPS)published in Canada
1996 WMA updates DOH (South Africa)
1993 CIOMS guidelines for biomedical research involving human subjects
1991 US CFR title 45, Part 46 issued CIOMS Guidelines for Epidemiological studies
1989 WMA updates DOH (Hong Kong)
1983 WMA updates DOH (Venice)
1981 US Common rule updated
1979 The Belmont Report
1975 WMA updates DOH (Tokyo)
1966 Dr. Beecher’s Article “Ethics and Clinical Research”
1964 World Medical Association (WMA) published the Declaration of Helsinki (DOH)
1947 The Nuremberg Code
1900 Walter Reed’s ‘consent’ for yellow fever experiments
Pre-1900 Edward Jenner smallpox vaccines
14. 18th and 19th Centuries
James Lind “scurvy study in sailors - Salisbury
Edward Jenner cowpox vaccine test
1897 Giuseppe Sanarelli yellow fever test
1900 Walter Reed established several [first ever]
“safeguards”
Self-experimentation
Only adults would be enrolled in research
Written informed consent
Reimbursement (inducement)
16. International Research Guidelines
Nuremberg Code (1947)
- As a result of WWII Nazi experiments
- First international code in research ethics
Voluntary consent absolutely essential
(restricting research with infants, children,
developmentally challenged, etc.)
Risk/Benefit Analysis essential to ethics review
Scientific Soundness is important to ethics review
17. The Nuremberg Code (1947)
The first provision of the code requires that “the voluntary
informed consent of the human subject is absolutely
essential.” The code provides other details implied by such
a requirement:
Capacity to consent
Freedom from coercion
Comprehension of the risks and benefits involved
Experiment to be conducted by highest qualified persons
The code on the web: http://ohsr.od.nih.gov/nuremberg.php3
18. The Declaration of Helsinki (DOH)
The World Medical Association created the Declaration of
Helsinki in 1964 and amended regularly since 1975
The main issues emphasized were:
“The well-being of the subject should take precedence over
the interests of science and society”
Consent should be in writing
Use caution if participant is in dependent relationship with
researcher
Limited use of placebo
Greater access to benefit
19. World Medical Association WMA (1964)
Respect for Persons – people are not a means
to an end; researchers have duty to protect life,
health, privacy and dignity of research participants
Standard of care must be best available, even
for control group
Proxy consent and assent for vulnerable
populations
20. More than 400 African-
American men with latent
syphilis were followed for the
natural course of the disease
rather than receiving
treatment.
Continued after penicillin
available
40 wives infected, 19 children
born with congenital syphilis
TUSKEGEE SYPHILIS STUDY,
ALABAMA ( 1932 – 1972 )
21. The Belmont Report (1979)
1972: the public became aware of the Tuskegee study
1974: the National Commission for the Protection of Human
Subjects of Biomedical and Behavioral Research was established.
1978: the commission submitted its report titled, The Belmont
Report: Ethical Principles and Guidelines for the Protection of
Human Subjects of Research.
Those principles respect for persons, beneficence and justice
are accepted as the 3 fundamental principles for the ethical conduct
of research involving human participants.
22. Council for International Organizations
of Medical Science (CIOMS) Guidelines (1993)
Informed consent
Research in developing countries
Protection of vulnerable populations
Distribution of the burdens and benefits
Role of ethics committees
23. Is it over?... Torvan trial in Kano,
Nigeria
Kano Trovan clinical trials in 1996, on pediatric age
group, during the worst ever meningococcal
meningitis.
Lack of proper Governmental authorization and
informed consent during the studies publicized in
2000, by Washington Post.
Court trial and release of investigation panel reports
stalled in Nigeria.
Suit for 5.8 billion USD moved to the USA and
report leaked there too.
Settlement out of court being discussed.
27. Very wide possibilities…
Identification of the genes responsible for human diseases,
Identification of the mutations underlying a vast number of
phenotypes
health care (medical), crop production and agriculture, non
food (industrial) uses of crops and other products
Examples:
biodegradable plastics, vegetable oil, biofuels), and
environmental uses.
manufacture of organic products (e.g. milk products)
Used to recycle, treat waste, cleanup sites contaminated
by industrial activities (bioremediation), and
to produce biological weapons.
28. Examples of the ethical issues in
research
• BENEFIT/HARM ANALYSIS
• VULNERABILITY (RISK-
VULNERABILITY MATRIX)
• INFORMED CONSENT
• FAIRNESS AND EQUITY IN RESEARCH
PARTICIPATION
• PRIVACY AND CONFIDENTIALITY
• CONFLICT OF INTERESTS (COI)
• INTEGRITY & PUBLICATION ETHICS
29. Benefits
Benefits to research subjects
Direct Benefit
Arising from the intervention being studied
Information that can influence care, e.g., diagnostic
Collateral “indirect” Benefit
Extra supervision from being in the research study (?)
Access to medical care not available for economic reasons
Unplanned or unanticipated benefits
Payments or incentives – benefits?
Benefits to society
• Specific new, effective intervention
• Knowledge which some time in the future may lead to effective interventions
30. Types of Risk…Cont.
Physical (medical) Risks:
1. Therapeutics: (Tuskegee expirement)
2. Preventive: (Trials of polio vaccine)
3. Diagnostic:
Irradiation:
- Teratogenic effect to the fetus.
- Carcinogenic effect.
Samplings:
- Biopsies: tissues that contain genetic information about the
participant.
- Surgical hazards.
- Too risky procedures (under anesthesia)
31. The Forgotten Risks
Social Risks:
Stigma (e.g. research on HIV-AIDS, STDs).
Emotional Risks:
On families when their children were chosen for trial
of new vaccine; research in war.
Psychological Risks:
Questionnaires with sensitive questions to
participants in sensitive positions, as to ask poor
people about their nutrition and houses.
Environmental Risks:
Manipulating environmental factors (Pathogenic
organisms and toxic chemicals).
32. Categorization of Risk
Risk is categorized by severity into:
1. Minimal Risk: As routine blood sample , throat swabs,
vaginal swabs, sputum exams
2. Above Minimal Risk: That can be minimized, and
within the toleration of the participant.
3. Too Risky: The most dangerous type, and the
Researcher should not be allowed to conduct a research
that endangers the life of the participants e.g. live cancer
cells , live virus
33. Clinical Equipoise
Clinical equipoise means a genuine uncertainty on
the part of the expert medical community about the
comparative therapeutic merits of each arm of a
clinical trial.
The tenet of clinical equipoise provides a clear
moral foundation to the requirement that the health
care of subjects not be disadvantaged by research
participants.
34. Minimization of Risk
Adequate facilities ,procedures and personnel for dealing
with emergencies .
Arrangement made for monitoring and detecting adverse
out comes .
All trials should be reviewed by a Data Safety Monitoring
Board (DSMB).
All potential toxins, mutagens or teratogens used should
be justified.
The specialized committees should make a complete risk
assessment for the use of the hazardous substances .
35. Minimization of Risk
For Drugs:
- Registration, its trade name, chemical name and pharmacological
class .
- Recommended dose, form of administration in the study.
- Known or possible interaction with other drugs, side effects and
adverse reactions.
- Placebo should be justified.
For Psychological Risks :
Sensitive questions for sensitive group like those with AIDS,
STDs, T.B, need to be asked by experiences researchers and ask
the help of psychologists may be needed.
Economic Risks :
Traveling cost can be solved out.
Absentees issues should also be solved out.
36. Minimization of Risk
Social Risks:
- The research should have potential to enhance the future
health of the society .
For vulnerable groups :
- Additional safeguards needed to protect there rights and
welfare .
For recruitment materials:
- (posters, newspapers, T.V, videos ……).
Should be acceptable if submitted.
37. Minimization of Risk
Legal :
- The risk should be reasonable in relation to the anticipated
benefits to the subjects or society.
- Privacy of subject should be adequately protected.
- For tissue samples containing genetics information the
subject should have option to withdraw at any time.
39. Definition
Vulnerable: “Vulnerable persons are those who are
relatively (or absolutely) incapable of protecting
their own interests due to insufficient:
power,
intelligence,
education,
resources strength,
or other needed attributes to protect their own interests.”
(CIOMS, 2002)
40. Who is Vulnerable?
M A K I N G U S E O F T H I S D E F I N I T I O N … L E T ’ S
B R A I N S T O R M !
www.amanet-trust.org
41. Who is Vulnerable?
1. WOMEN
Women in the reproductory age group are usually excluded
in drug/vaccine studies where the possible effects on fetus
are not known.
As justice to women, their health conditions should be
addressed through involving them in research.
Types of research that benefit women directly include,
obstetrics and gynecology, sexually transmitted infections,
vitamin studies etc.
42. Who is Vulnerable?
2. PREGNANT WOMEN
Should be awarded special protection because of additional
health concerns during pregnancy and the risk of damage to
the fetus.
Pregnant women must be excluded from research unless the
purpose is to meet the health needs of the mother, and
The fetus will be placed at risk only to the minimum extent
necessary to meet such needs or
The risk to the fetus is minimal
43. Who is Vulnerable?
3. CHILDREN
Particularly vulnerable group. The major ethical issue for
involving children is that parents are the primary decisions
makers for their minor children.
There must be no undue inducement to participate for
parent,
guardian or child, although reimbursement of expenses is
allowed.
A “small gift” to the child after completion of the research is
however acceptable.
44. Requirements for involving
in Research
The purpose of the research is to obtain knowledge
relevant to the health needs of children
A parent or legal representative of each child should give
permission;
The agreement (assent) of each child has been obtained to
the extent of the child`s capabilities; and
A child`s refusal to participate or continue in the research
should be respected.
45. Assessment of Risk in children
Minimal Risk- risk in relation to normal experience of
average, healthy normal children – daily life/routine physical
psychological exams
Minimal Risk varies with age but not social status, illness or
circumstances
Consultation with experts – pediatricians , social workers etc
46. Who is Vulnerable?
4. MENTALLY ILL / MENTALLY HANDICAPPED PERSONS
Is he/she capable of self-determination?
Respect for the immature and the incapacitated may require
protecting them as they mature or while they are incapacitated
(Belmont Report)
It is usually that informed consent will be provided by a
surrogate/ legal representative of that person.
The golden rule for involving mentally ill or handicapped people
is that ; The objections of these subjects to involvement
should be honored, unless the research entails pro-
providing them a therapy unavailable elsewhere.
47. Who is Vulnerable?
5. THE ELDERLY
Old age alone does not render a person incapable of
consenting to health research.
In the absence of any indication to the contrary, elderly
patients are generally assumed to be competent to
consent to research.
However, consideration should be given to the possibility
of mental deterioration, the ability to comprehend, and
the dependence and vulnerability of the elderly
48. Who is Vulnerable?
6. PRISONERS
Prisons are organizational structures exacerbate vulnerability of
the incarcerated individuals.
They have limited economic power, inadequate protection of
human rights, limited availability of health care and treatment
options.
The prison structure makes the incarcerated prisoners confined,
stressed, crowded, psychologically devastated with symptoms
such as psychosis, severe depression, and complete social
withdrawal.
49. Who is Vulnerable?
7. CAPTIVE/DISPLACED/RETURNING POPULATIONS
Have constrained movements and choices
Refugees, those in police custody, and displaced population,
Hospitalized patients, students, institutionalized persons and
military personnel.
Readily available for research activities for extended periods,
enhancing their attractiveness to research enterprise.
Researchers should always have to be sure if participant’s
decision making capacity is not compromised.
50. How to Decide?
Nature and degree of risk
The condition of the particular population involved and,
The nature and level of the anticipated benefits.
Relevant risks and benefits must be thoroughly arrayed in
documents and procedures used in the informed consent
process
51. Assessment of Risk-
Vulnerability
Research Risk depends on both Level of Invasiveness
(physical, psychological or emotional) and Vulnerability of
participants.
Vulnerability is generally a pre-existing condition, in that it
exists regardless of whether the research is conducted or not.
It can be inherent or situational.
52. Tri-Council Policy Statement
Ethics Review (Cont.)
Invasiveness: consider the physical, psychological,
emotional and legal harms that could be caused by
or exacerbated by the research.
Group Invasiveness
Vulnerability Low Medium High
Low Exp. Exp. Full
Medium Exp. Full Full
High Full Full Full
54. Conclusion
Vulnerability is considered to offer better protection, not to
stop
research on the vulnerable
Vulnerable groups should not be denied their right to
participate in relevant research
The risk assessment varies with the degree of vulnerability
56. Definition
“Autonomous authorization of a medical intervention…by
individual patients/participants“
(Beauchamp and Faden, 2004)
It's the practical expression of patient's autonomy, and the
respect for him/her personality
57. Components of FIC:
1. "Disclosure" refers to the provision of relevant
information by the clinician and its comprehension
by the patient.
2. "Capacity" refers to the patient's ability to
understand the relevant information and to
appreciate those consequences of his or her decision
that might reasonably be foreseen.
3. "Voluntariness" refers to the patient's right to
come to a decision freely, without force, coercion or
manipulation.
59. 1. Disclosure
This refers to the process during which physicians
provide information about the proposed research
to the participant.
60. Eight Required Elements
[45 CFR 46.116(a) & 21 CFR 50.25]
1. Statement that study in research and information on
purposes / duration / procedures / experimental
procedures
2. Reasonably foreseeable risks or discomforts
3. Reasonably expected benefits
4. Alternative procedures
61. Eight Required Elements Cont.
[45 CFR 46.116(a) & 21 CFR 50.25]
5. How confidentiality will be maintained
6. Information on compensation for injuries (unless
minimal risk)
7. Contact persons for information on research, injury,
subject’s rights
8. Voluntary participation, no penalty or loss of benefits for
refusal or withdrawal
62. Six Additional Elements
1. Statement that there may be risks which are unforeseeable
2. Under what circumstances investigator could terminate
subject’s participation
3. Additional costs to subjects
4. Consequences of subject’s withdrawal from research
5. Statement that will be told of new findings
6. Approximate number of subjects in study
63. Forms of Consent
Normally, should be provided by participants
themselves.
• Deferred consent: is where the subject is entered into a
research study and consent is gained from surrogates after a
specified period of time for continuation of the subject’s
inclusion in the trial.
• Prospective informed consent : represents an attempt to
canvass support in advance from a population considered at
risk of developing a serious illness.
• Surrogate consent (SDM): ideally a substituted judgment
made by a person responsible for health care decision-making
for a particular patient under the relevant legislation
64. Waiver of Informed Consent
REC must find and document that the following criteria
have been satisfied:
Poses no more than Minimal risk research
Waiver or alteration will not adversely affect the rights and
welfare of the subjects
Research could not practicably be carried out without the waiver
or alteration
Does not involve a therapeutic intervention
Subjects will be provided with additional pertinent information
All of the above must apply
65. Documentation of Informed
Consent
Written consent document
Language understandable to the subject or the subject’s
Legally Authorized Representative (LAR)
Signed by subject or subject’s LAR
Copy SHALL be given to subject
Opportunity to read before signing
66. Principles for Providing Information to
the Participant:
Make it clear; avoid jargon
Use language appropriate to the patient's level of
understanding in a language of their fluency
Pause and observe patients for their reactions
Invite questions from the patient and check for
understanding
67. Principles for Providing Information
the Participant: Cont.
Invite the patient to share fears, concerns, hopes and
expectations
Watch for patients' emotional response: verbal and non-
verbal
Show empathy and compassion
Summarize the imparted information
Provide contact information (and other resources)
68. 2. Capacity:
Refers to the presence of a group/set of functional abilities a
person
needs to possess in order to make a specific decisions
(Griso and Applebaum, 1998).
These include:
To UNDERSTAND the relevant information
To APPRECIATE the relatively foreseeable consequences
of the various available options available.
69. 3. Voluntariness:
Refers to a participant’s right to make participation
decisions free of any undue influence.
Influences include:
Physical restraint or sedation
Coercion involves the use of explicit or implicit threat to
ensure that the treatment is accepted
Manipulation involves the deliberate distortion or omission
of information in an attempt to induce the subject’s
participation
70. Voluntariness
Free of undue influence
Persuasion: appeals to reason
Manipulation
Coercision: explicit or implicit threats
Force: restraint or sedation
71. MANIPULATION
Distortion of facts or omission
Non-coercive alternation of choices
Undue financial payment
Undue influence, government funding only at grade
eight for hpv
72. Practical Challenges to a "Fully Informed
Consent"
Diagnostic uncertainty
Complexity of medical information
Linguistic and cultural differences
Overworked health personnel
Paternalistic approach in doctor-patient relationship
in developing countries, including Sudan.
73. Informed Consent from Children
Written Parental/Guardian consent only required for
those below the “legal age”
Assumption : best interests of the child should be
regarded
Both parents of the child should sign or just one?
Institutionalised children?
Children without any recognisable legal guardian?
74. Assent
After the age of seven and below legal consenting
age (which is different for different countries
depending on regulations) those who are
competent to understand the opinion of the child
should be respected
“A child’s affirmative agreement to participate in
research. Mere failure to object should not be
construed as assent” Silence Assent
75. Assent
Waiver of parental consent may be granted in
adolescent research in certain circumstances i.e.
drug abuse, sexual behaviour etc.
Assent documents may include – age appropriate
information sheets and forms where applicable
77. Privacy
The right to be left alone and to keep
personal information inaccessible to
others (the condition of limited access
to a person)
78. Privacy
Relates primarily to Process of clinical
examination and collecting data
Often Challenging in Natural Environment
Can inconvenience research participants
Can encounter participants in public
Procedures and processes can compromise privacy
Some institutions and cultures not accustomed to
privacy, or do not value it
79. Infringements of privacy
Infringements is justified under
certain circumstances; if:
1. Necessary for research conduct
2. Doesn’t create harm to
participants
3. There is societal benefit
80. Confidentiality
- The duty to respect the research participant’s
confidence that the researcher/doctor will not
disclose the information he/she received as part of
research of health care.
- How someone will deal with the information that
was disclosed to him in confidence
- Failure to keep private information is an infringements
of confidentiality
- Deliberate
- Accidental
81. Measures to respect confidentiality
Avoid identifiable data
Encode the collected data
Limit access to data
Keep in password-protected PC
Destroy the original copies after analysis, or
publication
Training of research team on confidentiality
Release information without identification
To each of the previous conditions, there are
ethically-acceptable exceptions
82. Breaking Confidentiality
Court order
Communicable diseases
Vulnerable person abuse/neglect
Driving/flying/machine safety
Dangerous patients
84. Important Considerations:
Retention of data after the study is complete
Secondary uses and linkage of data (i.e. databases)
How much personal information is actually
necessary for the study?
86. What is an interest?
• An interest may be defined as a commitment,
goal, or value held by an individual or an
institution.
• Examples include a research project to be
completed, gaining status through promotion or
recognition, and protecting the environment.
Interests are pursued in the setting of social
interactions.
87. What is COI?
• COI exists when two or more contradictory interests
relate to an activity by an individual or an institution.
• Conflicts of interest are “situations in which financial or
other personal considerations may compromise, or have
the appearance of compromising, an investigator’s
judgement in conducting or reporting research.” AAMC,
1990
88. What is COI? Cont.
• “A conflict of interest in research exists when the
individual has interests in the outcome of the research
that may lead to a personal advantage and that might
therefore, in actuality or appearance compromise the
integrity of the research.”
NAS, Integrity in Scientific Research
89. Levels of COI
• Researchers
• The REB should assess the likelihood that the
researcher’s judgment may be influenced, or
appear to be influenced, by private or personal
interests, and assess the seriousness of any harm
that is likely to result from such influence or
from the mere appearance of undue influence
(TCPS, 200)
90. Levels of COI
Conflicts of Interest by REB Members
• It is of the highest importance that members of
the REB avoid real or apparent conflicts of
interest .
• For example: when their own research projects
are under review by their REB or
• when they have been in direct academic conflict
or collaboration with the researcher whose
proposal is under review.
91. Levels of COI
Institutional Conflicts of Interest
• Situations may arise where the parent organization
has a strong interest in seeing a project approved
before all ethical questions are resolved.
• The REB must act independently from the parent
organization.
• Institutions must respect the autonomy of the REB
and ensure that the REB has the appropriate
financial and administrative independence to fulfill
its primary duties.
92. What comprises COI?
• Stock ownership
• Paid employment Board membership
• Patent applications (pending or actual)
• Research grants (from whatever source)
• Travel grants and honoraria for speaking or
participation at meetings
93. What comprises COI? Cont.
• Gifts Membership of lobbying organizations
• Relationship with the National Research Ethics
Review Committee, or with possible reviewers of the
paper
• Relationship with organizations and funding bodies
Membership of a government advisory board
94. Is it always bad?
COIs may result in:
1. Loss of objectivity
2. Reordering of priorities towards applied
research
3. Degradation of the nature of science as an
open and collegial enterprise
4. Exploitation of trainees
5. Transfer of time and interest to Commercial
ventures
95. • In May 2004, the pharmaceutical giant Pfizer
agreed to pay $430 million to settle a lawsuit by
a former employee turned whistle-blower, who
was joined in the lawsuit by the U.S. federal
government and 11 state governments.
• The lawsuit exposes various marketing practices
by the company Warner-Lambert – later bought
by Pfizer.
96. • Leading academic researchers were
paid to deliver promotional lectures
at educational events and to publish
favorable reports on the off-label use
of its epilepsy drug, Neurontonin.
L. Kowalczyk “Pfizer Drug Strategy Probed: States Question Marketing Tactics
for Neurontin,” Boston Globe, October 18, 2002,
97. Conflicts Can Occur at all Levels of
Research
• In reviews/awarding of grant
• In ethics review of grant
• In recruitment of participants
• In analysis of data
• In presentation of data
98. The Case of Nancy Oliveiri
• In 1996, Olivieri found that the drug she was
researching (deferiprone, active iron-chelating
agent ) at the Hospital for Sick Children in Toronto
was showing unexpected potential risks to some
patients in the trials.
• The drug company sponsoring her research
abruptly terminated the trials and issued warnings
of legal action against Olivieri should she inform
her patients at the Hospital for Sick Children of the
risks, or publish her findings.
99. The Case of Nancy Oliveiri Cont.
• The manufacturer (Apotex) issued more legal
warnings to deter Dr Olivieri from
communicating this second unexpected risk of
L1 to anyone.
• However, she published her findings in the New
England Journal of Medicine and
100. The Case of Nancy Oliveiri Cont.
• She was subsequently dismissed from her
position as Director of the Hospital for Sick
Children Program of Hemoglobinopathies.
• Apotex was planning to donate USD 100 Million
to the University of Toronto
101. The Case of Nancy Oliveiri
• After more than seven years of legal battle, an
independent committee of inquiry into the
matter vindicated Olivieri and concluded that
neither the university nor the hospital
offered her appropriate support in her
conflict with the drug company.
• Olivieri was reinstated to her position at the
Hospital for Sick Children and her actions have
also been vindicated by several other
independent reports.
102. The other side of the story
• Deferiprone is the only effective orally active
iron-chelating agent licensed for the treatment
of patients with thalassaemia major and other
disorders of transfusional iron overload.
• It is the only alternative to deferoxamine—a drug
that has to be given by daily subcutaneous
infusions and fails in many patients worldwide
because of the lack of compliance, high cost,
toxicity, or hypersensitivity.
103. The other side of the story
• No other clinicians using the drug had found
evidence for long-term liver damage and her
interpretation of the data was immediately
questioned in letters to the New England
Journal of Medicine.
• Four of her patients in whom liver fibrosis had
been suggested also had hepatitis C and all five
had iron overload—both causes of liver fibrosis.
105. Practical Steps to resolve
• Disclosure / transparency
• Stringent analysis of COI,
• Review of contracts between funders and researchers
• Close external monitoring
• Blinding of study, when possible
• Restrict review of colleague’s work
• Peer review of manuscripts
107. What is Ethical Review?
It is a process by which research proposals are
reviewed for their compliance and accordance with
the national/international ethical principles &
guidelines for research involving human subjects.
108. Research Requiring Ethics Review
All research involving living human subjects by
collecting identifiable information or materials
including:
Research with human remains, cadavers, tissues,
biological fluids, embryos and fetuses.
Interviews, surveys and questionnaires.
Secondary data analysis of data from living human
subjects.
109. Research exempt from Ethics
Review:
Research about living individuals in the public arena or
artists, based exclusively on publicly available
information.
Participant observation of public demonstrations,
political rallies and public meetings.
Quality assurance studies, performance reviews or
normal educational testing.