Transcript Framework for responsible research

Responsible Conduct of Research:
Research Involving Human Participants
www1.carleton.ca/curo/ethics-and-compliance/ethics
Framework for responsible
research
The Tri-Council (SSHRC, NSERC, and CIHR) funds research
in Canada and as such researchers and institutions are
responsible for the use of those funds and the integrity of
the research.
 Under the RCR policy researchers shall conduct
research with honestly, accountability and be open
and fair.
 Researchers shall follow the requirements of their
institutional policies and professional or disciplinary
standards.
 And, researchers shall comply with applicable laws
and regulations.
Responsible Conduct of
Research
 a. Using a high level of rigour in proposing and performing
research; in recording, analyzing, and interpreting data; and in
reporting and publishing data and findings.
 b. Keeping complete and accurate records of data,
methodologies and findings, including graphs and images, in
accordance with the applicable funding agreement, institutional
policies and/or laws, regulations, and professional or
disciplinary standards in a manner that will allow verification or
replication of the work by others.
 c. Referencing and, where applicable, obtaining permission for
the use of all published and unpublished work, including data,
source material, methodologies, findings, graphs and images.
Responsible research
 d. Including as authors, with their consent, all those and
only those who have materially or conceptually
contributed to, and share responsibility for, the contents
of the publication or document, in a manner consistent
with their respective contributions, and authorship
policies of relevant publications.
 e. Acknowledging, in addition to authors, all contributors
and contributions to research, including writers, funders
and sponsors.
 f. Appropriately managing any real, potential or
perceived conflict of interest, in accordance with the
institution's policy on conflict of interest in research, in
order to ensure that the objectives of the Framework
(Section 1.3) are met.
Breaches of Research
Integrity Policy
 Fabrication: Making up data, source material, methodologies
or findings, including graphs and images.
 Falsification: Manipulating, changing, or omitting data, source
material, methodologies or findings, including graphs and
images, without acknowledgement and which results in
inaccurate findings or conclusions.
 Destruction of research records: The destruction of one's
own or another's research data or records to specifically avoid
the detection of wrongdoing or in contravention of the
applicable funding agreement, institutional policy and/or laws,
regulations and professional or disciplinary standards.
 Plagiarism: Presenting and using another's published or
unpublished work, including theories, concepts, data, source
material, methodologies or findings, including graphs and
images, as one's own, without appropriate referencing and, if
required, without permission.
 Redundant publications: The re-publication of one's
own previously published work or part there of, or data,
in the same or another language, without adequate
acknowledgment of the source, or justification.
 Invalid authorship: Inaccurate attribution of
authorship, including attribution of authorship to persons
other than those who have contributed sufficiently to
take responsibility for the intellectual content, or
agreeing to be listed as author to a publication for which
one made little or no material contribution.
 Inadequate acknowledgement: Failure to
appropriately recognize contributions of others in a
manner consistent with their respective contributions
and authorship policies of relevant publications.
 Mismanagement of Conflict of Interest: Failure to
appropriately manage any real, potential or perceived
conflict of interest, in accordance with the Institution's
policy on conflict of interest in research, preventing one
or more of the objectives of the Framework (Section
1.3) from being met.
So, why an RCR policy?
A Brief History of
Human Research Ethics
Don’t end up on thin ice!
Nazi experiments of WWII
Experiments included
 Experiments on twins: of the 1500 twins used by Josef
Mengele less than 200 survived. These were children.
 Freezing experiments
 Malaria experiments
 Mustard gas experiments
 Sea water experiments (drinking sea water)
 Sterilization experiments
 Incendiary bomb experiments
Nuremberg Doctors’ Trials
 August 19, 1947, the doctors captured by
Allied forces were put on trial in USA vs.
Karl Brandt et al., which is commonly
known as the Doctors’ Trial.
 Several doctors argued in that there was
no international law regarding medical
experimentation they had done nothing
wrong.
Nuremberg Code 1949
 The doctors were found guilty and in response to
this claim of no international law the Nuremberg
Code was introduced as the first international
ethical standard for medical research.
 There were 10 points to the Nuremberg code and it
is the first point that would become the heart of all
research ethics codes.
Free and informed consent
The voluntary consent of the human subject
is absolutely essential.
This means that:
 The person involved should have legal capacity to
give consent.
 They should be so situated as to be able to exercise
free power of choice, without the intervention of any
element of force, fraud, deceit, duress, overreaching, or other ulterior form of constraint or
coercion;
 They should have sufficient knowledge and
comprehension of the elements of the subject matter
involved as to enable him to make an understanding
and enlightened decision.
The Nuremberg Code did not
stop unethical research
 The Tuskegee Experiment
was conducted by the
U.S. Public Health Service
and is “the longest nontherapeutic experiment
on human beings in
medical history.”
Tuskegee Syphilis Study
 From 1932-1972 the United States Public
Health Service conducted a study of 399
poor, mostly illiterate black sharecroppers
with syphilis.
 The participants believed they were
receiving free medical care and the true
purpose of the study being revealed.
 They were never informed they had
syphilis and were never treated for the
disease.
Purpose and outcomes
 The purpose of the study was to determine if patients
suffering from syphilis were better off not being treated
with present day toxic remedies.
 Patients treatment was intentionally denied and many
were given placebo treatments—in order to observe the
fatal progression of the disease.
 At the end of the study only 74 participants were still
alive:
 28 of the men had died directly of syphilis,
 100 were dead of related complications,
 40 of their wives had been infected,
 19 of their children had been born with congenital
syphilis.
Revelations of similar study
 In 2011 it is revealed that the US government with
the cooperation of the Guatemalan government in
the 1940’s deliberately infected hundreds of
Guatemalans; including prostitutes, mentally ill
patients and prisoners, with gonorrhea and syphilis
to test STD vaccines.
 None of those infected had given their consent.
Recent revelations from Canada
 In 2013 Ian Mosby uncovered an
unethical study involving
Aboriginal nutritional
experiments
 Between the 1940’s and 1950’s,
1300 aboriginal persons were
subjected to experiments – most
were children
 Government officials were aware
of the study
The study included…
 1942: 300 Norway House Cree, of that
group, 125 were selected to receive
vitamin supplements which were withheld
from the rest.
 1947: plans were developed for research
on about 1,000 hungry aboriginal children
in six residential schools in Port Alberni,
B.C., Kenora, Ont., Schubenacadie, N.S.,
and Lethbridge, Alta.
Specific studies
 One school deliberately held milk rations for two years to less
than half the recommended amount to get a 'baseline'
reading for when the allowance was increased.
 At another, children were divided into one group that received
vitamin, iron and iodine supplements and one that didn't.
 One school depressed levels of vitamin B1 to create another
baseline before levels were boosted. A special enriched flour
that couldn't legally be sold elsewhere in Canada under food
adulteration laws was used on children at another school.
 So that all the results could be properly measured, one school
was allowed none of those supplements.
 Many dental services were withdrawn from participating
schools during that time. Gum health was an important
measuring tool for scientists and they didn't want treatments
on children's teeth distorting results.
In summary…
“They knew from the beginning that the
real problem and the cause of
malnutrition was underfunding. That was
established before the studies even
started and when the studies were
completed that was still the problem."
– Ian Mosby
Declaration of Helsinki (1964)
 Revised and amended in 1975, 1983, 1989, 1996,
2000, 2002, 2004 and 2008.
 The World Medical Association established
recommendations guiding medical doctors in
biomedical research involving human participants.
 The Declaration governs international research
ethics and defines rules for "research combined
with clinical care" and "non-therapeutic research."
 The Declaration of Helsinki is the basis for Good
Clinical Practices (GCP) used today.
Some key principles in the
Declaration
 Informed consent
 Minimizing risk
 Adhering to an approved research plan/protocol
 Research protocols should be reviewed by an
independent committee prior to initiation
 Research should be conducted by
medically/scientifically qualified individuals
 Risks should not exceed benefits
Violations continue
 Stanley Milgram’s (1960’s) obedience study.
 The Aversion Project (1971-89)South Africa’s
apartheid army forced cures on white lesbian and
gay soldiers.
 Stanford Prison Experiment (1971)
 Nuu-chah-nulth blood samples (1980’s) British
Columbia aboriginals blood samples were used for
another purpose
The most famous cells in the
world
Henrietta Lacks
Her living cells
HeLa Cells
 In 1951 cancerous cervical cells were removed
from Henrietta Lacks without her consent
 Dr. George Gey successfully created a living line of
cells from this sample
 They were named HeLa, using the first two letters
of her first and last name
Results
 A living cell line meant they could be reproduced
and used in research.
 HeLa cells were used by Jonas Salk to test the first
polio vaccine, the cells have been used in cancer
research, AIDS research, radiation studies, gene
mapping, etc.
 According to author Rebecca Skloot, The Immortal
Life of Henrietta Lacks (2010), "more than 60,000
scientific articles had been published about
research done on HeLa, and that number was
increasing steadily at a rate of more than 300
papers each month.”
 The tissue sample was taken without her consent
and the living cells are a commercial product.
 Henrietta's family did not know until the 1970’s
that she was the source of these cells.
 Her children and grandchildren were asked to
provide blood samples for further studies.
Genome mapping
March 2013: European Molecular Biology Laboratory
published the genome of a line of HeLa cells, making
it publicly available for downloading.
Lacks family reaches an
agreement with NIH
 Genome study was taken down from the European Molecular
Biology Laboratory website.
 NIH funded research at the University of Washington was about
to publish a genome sequencing piece on the HeLa cells when
the Lacks family said “not without our consent.”
 the data from the genome studies should be stored in the
institutes’ database of genotypes and phenotypes.
 Researchers who want to use the data must apply for access and
will have to submit annual reports about their research.
 The HeLa Genome Data Access working group at the NIH will
review the applications. Two members of the Lacks family will be
members.
 The agreement does not provide the Lacks family with proceeds
from any commercial products that may be developed from
research on the HeLa genome.
Research Ethics in Canada
The Tri-Council Policy Statement: Ethical Conduct
for Research Involving Humans, 2nd Edition (2010):
Know as the TCPS, the policy applies to all
research institutions (universities, colleges and
hospitals) that are eligible to receive agency
funding.
Core Principles of the TCPS
Respect for Persons
 Respecting a person's autonomy
 Recognizing and respecting diminished autonomy
Concern for Welfare
 Quality of life including physical, mental and
spiritual health, economic and social
circumstances.
Justice
 Fair and equitable treatment
Who ensures ethical research?
 The researcher
 Research Ethics Boards (REBs)
 The public, by making researchers, REB’s
and research institutions responsible for
their actions
Research Ethics Boards
Carleton University has two REBs:
 The Carleton University Research Ethics Board
(everything but psychology)
 The Carleton University Ethics Board for
Psychological Research
What does an REB do?
REBs are mandated to:
 approve
 reject
 propose modifications to
 suspend or terminate
any proposed or ongoing research that is
subject to ethics review.
REB review is required when…
Article 2.1: The following requires ethics review and
approval by an REB before the research commences:
 research involving living human participants;
 research involving human biological materials, as well
as human embryos, fetuses, fetal tissue, reproductive
materials and stem cells. This applies to materials
derived from living and deceased individuals.
Exceptions to REB review
 Publically available information (Article 2.2)
 Observation of people in public places (Article 2.3)
 Secondary use of anonymous data (Article 2.4)
 Quality assurance and improvement studies
(Article 2.5)
 Creative practices (Article 2.6)
Key parts to an ethics protocol
 Project description (must be clear)
 Participants (who are they)
 Recruitment (how will you identify and recruit them)
 Risks (what are the risks of the study to participants)
 Benefits (what are the benefits to participants)
 Consent (how will you secure participant consent)
 Use of data (how will you use the information
participants provide)
Be clear, and concise
 Your project description must avoid all jargon (the
REB is not composed of experts in your field)
 Acronyms must be spelled out once
 Define or clarify your use of terms
 Keep to the point (limit 200 words)
Participants
 Research participants can be a random
sampling of the general population or
specific group.
 The participant group will in part
determine the research method,
recruitment, risks and consent process.
Vulnerable populations
 People without power
 Children
 Those traditionally excluded from research
 The elderly
 The displaced
 Circumstances that make a participant
vulnerable
Recruitment
 By which means will you identify potential
research participants?
 How will you make contact with potential
participants (poster, email, letter)?
 Recruitment is specific to the study and it
must make sense in terms of the study.
Recruitment & risk
 Are potential participants at risk if they
take part in this study?
 Are potential participants a vulnerable
population?
(How do you recruit them and keep them
safe?)
Risk to participants
 Your responsibility as a researcher is to be honest
about the risks to participants, to inform them of
those risks and take steps to minimize the risks.
 Risk can be one or a combination of the following:
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Physical
Emotional
Psychological
Professional
Social
Legal
Spiritual
Reducing risks
Several parts of a study determine the risk:
 What is being done (experiment)
 What is being asked (qualitative)
 The location of the research
 The physical, emotional and mental health of
participants
Benefits of research
 Most research does not directly benefit research
participants.
 Research benefits society as a whole and
contributes to the body of knowledge.
 Risks should not outweigh the benefits.
Informed Consent
The heart and soul of research ethics is full and
informed consent:
 Participants must be informed of everything
that is required of them.
 There can be no undue influence, or threat to
take part in a study.
 No excessive incentive to take part in the study.
Special Considerations
 Do participants have special needs?
Example: Children, seniors, developmentally
challenged persons
 Can the participants give informed consent? If not, who
can?
Consent is ongoing
 Researchers have an obligation to inform participants of all
information relevant to their ongoing participation in the
research
 If a project is modified the researcher must inform the
participant of the change. The participant has the right to
decline further participation or to withdraw from the study.
 A child who reaches the age of consent during a study must
be given the opportunity to consent on their own behalf.
Incidental findings
 A discover is made during the course of the study.
 The researcher may be obligated to report those
findings.
 Child abuse
 Fraud
 Health issues
 In some cases a researcher is legally obligated to
disclose (duty to report)
Waiving consent
 In some instances, consent may not be
required:
 Minimal risk research where there is no
adverse effect on the participant
 Prior consent would make it impossible to
carry out the research
 Research does not involve a therapeutic
intervention
Written vs. Oral consent
Written consent is the standard unless there is a
practical or cultural reason to obtain oral consent:
 Telephone survey
 Oral tradition or “word as bond”
 Handshake
 Impractical (interviews with street people)
All consent must be documented.
Anonymity and Confidentiality
 These are not the same thing.
 Anonymity is the identity of the
participant (name, address, work position
and location, physical markers, DNA)
 Confidentiality is about the data and
information the participant provides
Anonymity
 Participants do not have to be anonymous.
 If the participant is well known, or is the
only person who can speak to an issue,
then you cannot reasonably offer
anonymity.
Use of data
 Your commitment to ethical research extends to
the safe and secure storage of data and the
proper use of that data
 Participants need to know what will happen with
their data. (Destroyed, stored for future
research on that topic, or stored and used for
related research
 Data cannot be used for another purpose
without the knowledge and consent of the
participant
Research ethics violations on
the use of data
Three major misuses of data include:
Falsification of data
Fabrication of data
Plagiarism
Falsification of data
Matthew Poore (Advanced Liquid Logic Inc.) engaged in
research misconduct by falsifying data, while conducting
research for National Institute of Allergy and Infectious
Diseases and National Institute of Health.
He knowingly and intentionally falsified reverse
transcription-polymerase chain reaction (RT-PCR) results
by reporting the results from previous experiments as the
actual results, when the experiments had not been
performed. When testing for HIV he also switched two
results from negative to positive and one vice versa.
He has entered a Voluntary Settlement Agreement for
three years and will have to have his research supervised,
and will not serve in any advisory capacity to Public Health
Service.
Plagarism
Pratima Karnik (Case Western Reserve University) engaged in
research misconduct by plagiarizing when conducting research
for The National Institute of Arthritis and Musculoskeletal and
Skin Diseases and National Istitutes of Health.
She plagiarized portions from a research grant application that
she reviewed and other scientific articles.
Dr. Karnik has entered a Voluntary Settlement Agreement where
her research must be supervised, the institution employing her
must submit a certification for all of her applications stating that
there is no plagiarized material and she cannot serve in any
advisory capacity to Public Health Service for two years.
Fabrication
Avi Chaudhuri, of McGill University, misused $159,500 of
research money. He used his McGill purchasing card to buy a
$19,500 mattress designed for people with limited mobility.
Following his mother’s stroke he purchased and shipped the
mattress and his mother to India. He claimed the mattress
was for a study on stroke victims in India.
There was no evidence that Mr. Chaudhuri had ever planned
a stroke study.
During the enquiry Mr. Chaudhuri said the mattress was in a
warehouse in India, but later acknowledged to that it was in
an apartment owned by his family in Calcutta.
Media, research & ethics
 Consider what has happen recently around
research and the media.
 MS liberation method:
Fast tracking clinical research
Is it safe?
Is it effective?
Voice of MS patients
Change your perceptive
 Consider your research project from the
point of view of those you are asking to
take part.
 Consider what the commitment from the
participant is to take part in the study.
 Look at the project through new eyes.
 Ask the questions a participant would ask.
Autism & MMR
 The results of this media investigation
continue to rock the world of research
 Some key elements of this study:
Shoddy research
Manipulation of research results
Abuse of children
Voice of parents
Autism study
 Andrew Wakefield, M.D., UK. Famous for
autistic enterocolitis. Basically he made the
case that the MMR (measles, mumps and
rubella) vaccine cause autism in children.
 In November 2004, Channel 4 in the UK
reported that Dr. Wakefield had applied for a
patent on a single-shot measles vaccine before
his campaign against the MMR vaccine.
 Other researchers could not duplicate his
findings.
Autism study
 On 28 January 2010, found Dr. Wakefield
guilty of approximately three dozen charges,
including 4 counts of dishonesty and 12
counts involving the abuse of developmentally
challenged children.
 His research has been declared fraudulent and
false. He has had his medical license revoked
and all publications on the MMR vaccine
pulled.
 He maintains several thousands of supporters,
especially parents of autistic children.
Why does this matter?
Final word…
“We must not see any person as an
abstraction, instead we must see in every
person a universe with its own secrets,
with its own treasures, with its own
sources of anguish, and with some
measure of triumph.”
- Elie Wiesel, from The Nazi Doctors and the
Nuremberg Code (1995) by George J. Annas &
Michael A.Grodi