Download 40_Krittaecho Siripassorn

Ethical challenges in research
during an epidemic outbreak
Krittaecho Siripassorn, MD
Chair of the IRB of BIDI
Bamrasnaradura Infectious Diseases Institute
Nov 2015
Background
In an outbreak situation
public health authorities undertake a rapid
response to document existence and
magnitude of epidemic and to implement
appropriate measures
timeliness is major requirement, for
research during outbreak
– thus the approval from IRB is an ethical
challenges in this situation
Background
Challenges in reviewing research in disease
outbreak
– Timeliness of IRB reviewing procedure
– Appropriateness of alternative mechanism of IRB
reviewing procedure
– Protection rights and welfare of individuals
– Outbreak investigation/research activities should be in
a timely manner to control the disease
How to comply with ethical requirement that research
be approved by IRB and still enable prompt response
when outbreak occurs
Research VS Public Health Practice
during outbreak
Public Health
Practice
Research
Research VS Public Health Practice
during outbreak
Public Health Practice
Research
 population surveillance, disease control and
prevention, and program development & evaluation
 collection information or human biological
specimens without ICF
 subject to public health laws and regulations, do not
typically undergo prospective ethics review
 Primary intent: “prevent or control disease or injury
and improve health, or to improve a public health
program or service”
Research VS Public Health Practice
during outbreak
Public Health Practice
Data & infromation
Retrospcetive study
of these data might be
difficult to approved
in some case of noncompliance and
substandard ethics
conduct
Research
human biological
specimens without ICF
 Study with Anonymous samples
without personal health information -->
difficult to generate valuable knowledge
 going back to get consent
from sampled individuals, which could
be logistically difficult, and almost
impossible
Example of research product from Public Health Practice
Ribavarin for Px patients infected with SARS
Leong HN. Trop Med Int Health.2004
Booth CM. JAMA 2003
Momattim H. Int J Infect Dis. 2013
Research VS Public Health Practice
during outbreak
Public Health Practice
Research
 require prospective independent review IRB, unless
they meet certain criteria for exemption
 Primary intent: “generate or contribute to
generalizable knowledge”
Research VS Public Health
Practice during outbreak
Public Health Practice
Epidemiologic
research
Research
Clinical trial
Research during outbreak (1)
Epidemiologic
research
Clinical trial
 well-established procedure for ethics review should apply to
all research conducted in a disease outbreak
 Generally, it’s procedure are likely to be blood drawing and
survey completion
 Vulnerable subjects are generally involved and need for
additional safeguard
Research during outbreak (2)
Macklin R, PLoS Negl Trop Dis. 2009
Epidemiologic
research
Clinical trial
 Committees could establish a procedure for disease
outbreak investigations esp. epidemiologic study
 A full, detailed protocol might not be submitted.
 A shorter document should be acceptable describing:
1. Background
2. Objective
3. study procedure
4. informed consent procedures
5. steps to protect the confidentiality of information
obtained from the individuals
Research during outbreak (3)
Macklin R, PLoS Negl Trop Dis. 2009
Epidemiologic
research
Clinical trial
ICF documents of the research during outbreak
 Main content should explain
1. That what they are consenting to is research, and not
routine activities carried out by public health practitioners
during a disease outbreak
2. Whether identifiable information is collected and how it is
collected
It is surely not necessary to include all 26 items listed as
“essential information for prospective research subjects” in the
CIOMS International Ethical Guidelines for Biomedical Research
There was an
announcement of
one MERS patient in
Thailand on June 2015
The case and close contacts
were finally transferred to our
institute (BIDI) for quarantine



Caused by Corona
virus
human to human
transmission with
unknown mechanism
occurred in health care
facilities in several
countries
Serology of healthcare workers
who exposed to a patient with MERS
To evaluate effectiveness of infection controlled
procedure of MERS-CoV in health care workers
who contact the MERS patient by measuring
antibody level to the MERS-CoV
Inclusion:
– Healthcare worker who take care the MERS patient or
Laboratory workers who involves with biological
sample
Study procedure:
– Two blood samplings from each subject (within 14 days
from exposure for the first blood sampling)
Wiboonchutikul S, with permission
IRB reviewing procedure
Draft a concept proposal
Experienced IRB members helped
the PI to develop the full protocol
Writing full protocol on Jul 7, 2015
Contact to all IRB members to
have an Emergency meeting on
Jul 9, 2015
Protocol submission on Jul 8, 2015
Minor revision
Emergency meeting: Jul 9, 2015
Protocol revision submitted on Jul 9, 2015
Primary reviewer reviewed and
approved the corrections
Protocol Approval on Jul 9, 2015
Research during outbreak (2)
Epidemiologic research
Repeated occurrence of
outbreak, eg chloera
Clinical trial
Outbreak with novel
disease-causing agents,
eg. SARS, MerCoV
Clinical trial/research during outbreak
Macklin R, PLoS Negl Trop Dis. 2009
Repeated occurrence of
outbreak, eg chloera
Outbreak with novel
disease-causing agents,
eg. SARS, MerCoV
 exact time of outbreak is unpredictable
 Outbreak area is predictable
 investigators can prepare a “model protocol,” for full
review to the IRB
1. Omitting items that are specific to the time and place of
the predicted outbreak
2. When the outbreak occurs, investigators can complete
the specific information for review by the committee
Clinical trial/research during outbreak
Macklin R, PLoS Negl Trop Dis. 2009
Repeated occurrence of
outbreak, eg chloera
Outbreak with novel
disease-causing agents,
eg. SARS, MerCoV
 exact time of outbreak is unpredictable
 Outbreak area is predictable
 investigators can prepare a “model protocol,” for full
review to the IRB
1. Omitting items that are specific to the time and place of
the predicted outbreak
2. When the outbreak occurs, investigators can complete
the specific information for review by the committee
Clinical trial/research during outbreak
Macklin R, PLoS Negl Trop Dis. 2009
Repeated occurrence
of outbreak




Outbreak with novel
disease-causing agents,
eg. SARS, MerCoV
difficult to study
epidemic was both rapid in its onset
causative agent is initially unknown
no existing approved treatment
protocols are in place
 Evidences of guideline of treatment for MERS generally
based on studies on SARS
 Retrospective studies (n = 6)
 Prospective cohort studies (n = 3)
 Randomized clinical trials (n = 4)
Emergency research ≠ outbreak
Emergency use exemption criteria:
– (1) a life threatening situation and no standard
treatment is acceptable
– (2) insufficient time to convene a quorum for
FB IRB approval
This rule can not generally apply for
research or trial during an outbreak
Take home message
ethical review and approval are needed for
an investigation of a disease outbreak
Timeliness of IRB procedure is a major
challenge for research during outbreak
– Can be improved by a various mechanism
such as model protocol, establishing an IRB
reviewing procedure for disease outbreak
research