01 - Mongal - Human Subjects Approvall

Training Workshop on Household Air Pollution and
Monitoring
March 21-25, 2016
Hotel Holiday Home
Paro, Bhutan
Human Subjects Approval
Mongal Singh Gurung
Member Secretary
Research Ethics Board of Health
Ministry of Health
Content Contributions from:
Lee See Muah, Ruth Macklin with other SERG members, Sheryl Vanderpoel, Dr Lungten Z
Wangchuk and Dr Pakila Drukpa
PresentationOutline
— Need for Ethical Review
— Basic Ethical Principles
— Research Ethics Board of Health (REBH)
WHYISETHICALREVIEWOF
RESEARCHNEEDED?
THETUSKEGEEEXPERIMENT
Ò
From 1932-1972, about 400 African American participants diagnosed
with syphilis were medically followed as part of a US Public Health
Service research study. The participants were provided:
É
free medical examinations
É
free transport to the clinic
É
free hot meals on examination days
É
free treatment for minor ailments
É
free burial
What’s the catch?
TheTuskegeeExperiment
Ò
Ò
Ò
Ò
Palliative treatments were provided initially because no cure was
available.
Only after penicillin became available was there a possibility of real
treatment. Yet, once available, although in the middle of the study,
penicillin was still not provided to the participants!
The experiment was established and conducted in order to study the
natural medical history of syphilis.
Important knowledge was obtained and published in reputable
journals, one such article was titled:
“Tuskegee Study of Untreated Syphilis in the Negro Male”
DoingBadintheNameofGood
v
v
Not until 1997, did the US government offer
an official apology. It was President Clinton
who formally apologized to the surviving
participants and their descendants.
Earlier a Commission had been established
to study the episode, and recommended
monetary compensation to the men who
were still alive, and to the families of those
who had died.
THENAZIEXPERIMENTS
High Altitude Experiments
March 1942 – August 1942
Experiments conducted at a
concentration camp for the benefit of
the German Air Force
Experimental subjects were placed in
the low-pressure chamber and
thereafter the simulated altitude therein
was raised
Many victims died
Freezing Experiments
August 1942 – May 1943
Experiments conducted at a
concentration camp for the benefit
of the German Air Force
Experimental subjects were forced
to remain in a tank of ice water for
periods up to 3 hours
Many victims died
Sea Water Experiments
July 1944 – September 1944
Experiments conducted at a
concentration camp for the benefit
of the German Air Force and Navy
Experimental subjects were
deprived of all food and given only
chemically processed sea water
The experiments caused great pain
and suffering and resulted in
serious bodily injury to the victims
WhatHappenedtotheNazis?
• Some escaped to other countries
including the United States. Many fled
to Brazil.
• 22 Nazi officers were arrested and tried at
the Nuremburg Trials. 12 were
sentenced to death by hanging
The Nuremberg Code
“It took the cruelty described at
Nuremberg to make the world realize it
had to do something that would protect
human subjects from inhumane
research.”
John Bryant (2000), President, CIOMS
AtRavensbruck
• Women were shot or
slashed on the legs.
• The wounds stuffed
with glass, dirt, and
bacteria cultures and
sewn shut
• Then treated with
experimental antiinfective agents.
UNIT731*DURINGTHESECONDSINO-JAPANESEWAR
ANDWORLDWARII
Ò
Ò
"Unit 731 was a covert biological and chemical
warfare research and development unit of the
Imperial Japanese Army that undertook lethal
human experimentation from 1937 until 1945.
It was responsible for some of the most notorious
war crimes carried out by Japanese personnel."
UNIT731*DURINGTHESECONDSINO-JAPANESEWARAND
WORLDWARII
Ò
ü
ü
ü
ü
ü
Vivisection
Vivisection without anesthesia, after infecting them
with various diseases.
limbs amputated to study blood loss. Removed limbs
were sometimes re-attached to the opposite sides.
Some prisoners' limbs were frozen and amputated
Limbs frozen then thawed to study the effects of the
resultant untreated gangrene and rotting.
Stomachs surgically removed and the esophagus
reattached to the intestines.
Parts of the brain, lungs, liver, etc. were removed from
some prisoners”*
*Last modified on 18 March 2014 from https://www.mtholyoke.edu/~kann20c/classweb/dw2/page1.html
Vivisectionprocedurewhilepatientisalive,
performedbyShiro Ishiihimself
UNIT731*DURINGTHESECONDSINO-JAPANESEWARAND
WORLDWARII
Ò
ü
ü
ü
Germ warfare attacks
“Prisoners injected with disease, disguised as vaccinations,
to study their effects.
To study the effects of untreated venereal diseases, male
and female prisoners were deliberately infected, often by
rape, with syphilis and gonorrhea, then studied.
Plague fleas, infected clothing, and infected supplies
encased in bombs were dropped on various targets. The
resulting cholera, anthrax, and plague were estimated to
have killed around and possibly more than 400,000
Chinese civilians”*
*Last modified on 18 March 2014 from https://www.mtholyoke.edu/~kann20c/classweb/dw2/page1.html
"Because of their brutality, Unit 731's
actions have since been declared by
the United Nations to have been
crimes against humanity."
*Last modified on 28 April 2010
THETHALIDOMIDESTORY
Ò
Thalidomide was first synthesized in 1954
Ò
Thalidomide was used as a sedative for symptoms of
morning sickness:
Ò
Thalidomide was marketed in Europe in 1957, however
never approved by the US federal authorities
É
“drug of choice for pregnant women”
É
“completely safe’”
WHATWENTWRONG?
Thousands of babies were born with multiple deformities…
The drug had been marketed without completing tests in participants,
never including pregnant women in initial pilot studies and without
completing appropriate tests in animal studies.
20th
CenturyResearchEthicsMilestones
ICH GCP
Common Rule 1991
CIOMS 1982
Consolidated HHS/FDA Regulations
Belmont Report
Declaration of Helsinki
1964
1981
1979
1972 Syphilis Study Exposed
1966 The Beecher Article (NEJM)
Nuremberg
Code
1947
The Thalomide Tragedy
US Human Radiation Experiments
The Nazi Experiments
1932 The Syphilis Study Begins
Trigger Events
Milgram Study
Kefauver-Harris Amendments
Food, Drug and Cosmetic Act 1962
Do we really need to do
research on humans?
Do we really need to do research on humans?
Ò
Is our knowledge of the human body complete ?
Ò
Is our understanding of human disease
comprehensive ?
Ò
Is medical treatment perfect ?
Ò
Is disease prevention absolute ?
Yes,asresearchis
designedto… …lead to generalizable new
knowledge which will
increase our understanding
of ourselves, our
relationship with others as
well as with the natural
world.
Researchisdesignedto:
v
enhance the quality of life (including being free
of disease)
v
alleviate suffering caused by disease and
disability
Hasthependulumswungtoofar?
People are now demanding the right to
be a research participant.
v HIV has changed the face of research
ethics and participation in research
studies
v
Hasthependulumswungtoofar?
Ò
Ò
From burden to benefit
From sacrifice to promise
“I believe the current tendency to see research as
largely beneficial and benign is just as erroneous as
the earlier tendency to view it primarily dangerous
and exploitative”
Robert J Levine, Keynote address,
The XXVIth CIOMS Conference,
February 1992
The Ethical
Dilemma..……
Knowledge
Risks
Complexity in the Guidance of Research Conduct:
Deconstructing that complexity with the Belmont Principles
A. Respect for persons
– Informed Consent , Access to
information
– Privacy of participants,
protection of confidential information
B. Beneficence
C. Justice
A. Respect for person
Information: Moral implications in research
— Information revealed may be extremely disturbing for the participant
(e.g., minors, violence)
— Research may include vulnerable groups, adolescents, trafficked
women
— Information about sexual matters are deeply personal and private
— Information received may be deeply distressing for the research worker
Respect for the person:
Maintaining Confidentiality: Legal implications
— Sensitive information about collateral illegal activities, human
trafficking, drug use may be obtained
— Will the information gathered harm the participants or/and
researchers?
— Statutory duty to inform the authorities
— Court order to compel disclosure
B. Beneficence: Harm and Benefits
— Does the research help participants?
— Can the research be used against participants?
— How is the research beneficial?
– Can the identified gaps be addressed?
Paragraph 5, Helsinki Declaration: …wellbeing of the
participants should take precedence over the interests
of science and society.
Beneficence: not just to participants but to groups
(communities, schools, workplace, hospitals…)
Harm from Stigmatization:
— A stigma is a mark of shame or discredit
— Double stigmatizations:
— Association of AIDS with homosexuality
— Association of AIDS and/or STIs with sex workers
— Association of a husband with sexual violence if wife is interviewed on the
subject
— Association of risky behaviour of teens to a particular school or community
— Association of limitations of employees to a hospital
— Researchers must evaluate whether or not their research could result
in such group harms and, if this is a possibility, minimize this risk
C. Justice
• People should be treated fairly. Selection of research
participants, must be unbiased and fair. Examples of
injustices:
•
Potentially risky research for undesirable
vulnerable groups
• Potentially beneficial research for favoured
groups
The prospect of gaining new scientific knowledge
need not
and
should not
be pursued at the expense of human rights and dignity.
གསོ་བའི་ ཞིབ་འཚ*ལ་ ,ན་.ོད་0མ་གཞག་ བཀོད་ཚ*གས།།
Research Ethics Board of Health
(REBH)
HISTORY
• 1960s ...Department of Health Services
•
•
two basic hospitals [31 hospitals (including 1 indigenous hospital)]
11 dispensaries [235 Basic Health Units and Sub-posts, 52 indigenous
units, and 562 Outreach clinics]
•
•
•
•
1984… Health Information Unit
1995 …Health Research and Epidemiology Unit
1999 …Bhutan HMIS
2001…Health Research Technical and Ethical
Committee
• 2009 … REBH (Officially – January 26, 2009)
ORGANOGRAM
Minister
BMHC
InternalAudit
Secretary
ResearchEthicsBoardof
Health(REBH)
BhutanHealthTrustFund
AFD
ICT
QASD
PPD
DoPH
HealthResearch&
EpidemiologyUnit
(secretariattoREBH)
DMS
March 24, 2016
39
AffiliationofREBH
1.
2.
SIDCER/FERCAP
•
NAREC
FWA(OHRP)
ProtocolManagementinREBH
March 24, 2016
41
StandardOperatingProcedures(SOPs)of
REBH
— 28 Sops
— 5th Revision
— Available online
TypesofReview
— Full Board Review
— Expedited Review
— Emergency Board Meeting
March 24, 2016
43
MeetingSchedules
• Board meetings
• February, April, June, August, October and
December (6/year)
• Protocol assessment time – one month
• Expedited reviews – two weeks
• Emergency meetings (as and when)
Listofdocumentsrequiredtobesubmitted
forinitialreview
— Application Form for Initial Review (It can be
downloaded from http://www.health.gov.bt/357-2/
Also, it’ll be provided on request)
— Research protocol/proposal including the itemized
budget and research project schedule or timeline
(final version) – Please write dated version number
on it
— Research/study tools (e.g. final version of
questionnaire, forms, guides. etc.) – Please write
dated version number on it
Listofdocumentsrequiredtobesubmitted
forinitialreview…continued
— Curriculum Vitae of all investigator(s).
— Informed Consent Form and Information Sheet
both in Dzongkha and English languages – Please
write dated version number on it.
—
For minor subjects (less than 18 years):
Informed Assent Form and Information Sheet both in
Dzongkha and English languages, and
— Informed Consent Form and Information Sheet both in
Dzongkha and English languages for their parents/legal
guardians
—
What is the role of IRB/EC?
THANKYOU