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Ethics Board & Submission_Online_Handouts_Apr2020 1
ETHICS BOARD & SUBMISSION
- DSRB / CIRB
Online Learning ModuleUpdated as of April 2020
Developing Clinical Research Professionals for the Nation
Training Disclaimer
This training and training materials are for educational and
informational purposes only.
This training material should be read in conjunction with the applicable
latest research policy and regulations from the learner’s research
organisation and/or institution, Singapore Regulatory Authority and
Ministry of Health.
Kindly note that all information and opinions presented in this training
and training materials were written to the best knowledge available at
the time of writing.
Ethics Board & Submission_Online_Handouts_Apr2020 2
Developing Clinical Research Professionals for the Nation
• Introduction to Institutional Review Board (IRB)
• Types of IRB in Singapore - CIRB vs DSRB
• Types of IRB review and outcome
Module Outline
Developing Clinical Research Professionals for the Nation
Introduction
Terms are used interchangeably:
Institutional Review Board (lRB)
Institutional Ethics Committee (lEC)
Ethics Committee (EC)
What is an IRB? (ICH GCP 1.31)
• An independent body
• Constituted of medical, scientific and non-scientific members
• Responsibility: Ensure the protection of the rights, safety and
well-being of human subjects
• By reviewing, approving, and providing continuing review of trial
protocol and amendments and of the methods and materials to
be used in obtaining and documenting informed consent of the
trial subjects
Ethics Board & Submission_Online_Handouts_Apr2020 3
Developing Clinical Research Professionals for the Nation
When the research study:
• Involves human subjects (ie. Clinical research)
• Is conducted at institutions or partner institutions under the
IRB’s purview (ie. Uses their facilities)
• Is conducted by, or under the direction of, a employee
under the purview of the IRB/healthcare cluster
• Involves patients from that IRB/healthcare cluster
When is IRB Review required?
Developing Clinical Research Professionals for the Nation
2 Major IRBs in SingaporeReviewing Clinical Research Studies
SingHealth
Centralised Institutional
Review Board
(CIRB)
National Healthcare Group
Domain Specific Review Board
(DSRB)
Ethics Board & Submission_Online_Handouts_Apr2020 4
Developing Clinical Research Professionals for the Nation
CIRB Purview
SingHealth Institutions
under CIRB purview
Partner Institutions
under CIRB purview
1. Singapore General Hospital
2. KK Women’s and Children’s Hospital
3. National Cancer Centre of Singapore
4. National Dental Centre of Singapore
5. National Heart Centre of Singapore
6. National Neuroscience Institute
7. Singapore National Eye Centre
8. Singapore Eye Research Institute
9. SingHealth Polyclinics
10.Bright Vision Hospital
1. Changi General Hospital
2. HCA Hospice Care
3. Singapore Civil Defence Force
4. Duke-NUS (Only applicable for
collaborative research studies with
SingHealth Institutions)
Developing Clinical Research Professionals for the Nation
NHG Institutions
under DSRB purview
Partner Institutions
under DSRB purview
1. Tan Tock Seng Hospital
2. National Skin Centre
3. Institute of Mental Health
4. Khoo Teck Puat Hospital
5. Yishun Community Hospital
6. NHG Polyclinics
1. National University Health System
• National University Hospital
• NUS Yong Loo Lin School of Medicine
• NUS Saw Swee Hock School of Public
Health
• NUS Faculty of Dentistry
• Alice Lee Centre for Nursing Studies
• Ng Teng Fong Hospital
• Jurong Medical Centre
• Jurong Community Hospital
• NUHS polyclinics
2. Agency for Integrated Care
3. Ang Mo Kio Thye Hua Kwan Hospital
4. Dover Park Hospice
5. Singapore Institute of Clinical Sciences
DSRB Purview
Ethics Board & Submission_Online_Handouts_Apr2020 5
Developing Clinical Research Professionals for the Nation
CIRB: Therapeutic Domains
A • Ophthalmology
• Psychiatry
• Neurology/Neurosurgery (including
sleep studies)
• Geriatric Medicine
• Nursing
• Health Service Research
B • Oncology
C • Cardiovascular Science
• Pharmacology
• Emergency Medicine
• Endocrinology
• Diagnostic Imaging
• Respiratory Medicine
D • Obstetrics/Gynaecology
• Anaesthesia (including acupuncture)
• Surgery
• ENT
• Dentistry
E • Gastroenterology
• Renal Medicine
• Rheumatology/lmmunology
• Dermatology
• Paediatric Medicine
• Family Medicine
F • Genetics
• Palliative Medicine
• Haematology (including
haematological malignancies)
• Pathology
• Sports & Rehab Medicine
• Allied Health
• Infectious Disease
Choose the appropriate domain to submit your clinical trial.
Developing Clinical Research Professionals for the Nation
A • Ophthalmology
• Psychiatry
• Neurology/Neurosurgery
• Genetics
• Geriatric Medicine
• Palliative Medicine
B • Oncology
• Hematology
• Pathology
• Paediatrics
• Respiratory Medicine
C • Cardiovascular Science
• Pharmacology
• Emergency Medicine
• Endocrinology
• Diagnostic Imaging
• Family Medicine (Non
organ/disease specific only)
D • Obstetrics/Gynaecology
• Anaesthesia
• Surgery
• ENT
• Dentistry
• Sports and Rehab Medicine
• Allied Health
E • Infectious Disease
• Gastroenterology
• Renal Medicine
• Rheumatology/lmmunology
• Dermatology
F Population Health (Does not review clinical trial)
• Health Services and Outcome Research
• Education Research
• Research on Prevention and Health
Promotion Programs
• Social and Behavioral Research
• Epidemiological Research
• Community-based Participatory Research
DSRB: Therapeutic DomainsChoose the appropriate domain to submit your clinical trial.
Ethics Board & Submission_Online_Handouts_Apr2020 6
Developing Clinical Research Professionals for the Nation
• There are 3 categories of IRB Review.
(Exempted, Expedited, Full Board Review)
• When drafting the application, you will have to select either:
or
• If the study does not meet the criteria for Exemption, the IRB will
further classify your Non-Exempted study into either:
1. Expedited Review Minimal Risk
2. Full Board Review More than Minimal Risk
(For Clinical Trials)
Exempted Non- Exempted
Types of IRB Review
Developing Clinical Research Professionals for the Nation
Studies under Exempt Category
Category 1 Normal educational practices and settings
Category 2 Anonymous educational surveys, interviews, or
observations
Category 3 Identifiable subjects in special circumstances
Category 4 Collection of existing publicly available or
unidentifiable data, documents, pathological
specimens
Category 5 Evaluation of public benefit or service programme
Category 6 Taste and food evaluation and acceptance studies
• Exemption means exemption from submitting “Continuing Review” application.
• Your study still needs to be submitted to IRB (ie. Initial application) to obtain approval
for “Exemption” from continuing review.
• If there are study amendments that may affect its exempt status, application must be
submitted to IRB for review.
Ethics Board & Submission_Online_Handouts_Apr2020 7
Developing Clinical Research Professionals for the Nation
1. No more than minimal risk to research subjects
2. Research is not classified
3. Identification of subjects and/or their responses does not
reasonably place them at risk or criminal/ civil liability or be
damaging to their financial standing, employability,
insurability, reputation, or be stigmatizing, unless
reasonable and appropriate protections will be
implemented so that risks related to invasion of privacy &
breach of confidentiality are not greater than minimal.
4. Belongs to one of the expedited review categories
Criteria for Expedited Review
Developing Clinical Research Professionals for the Nation
“Probability and magnitude of harm or discomfort
anticipated in the research are not greater in and of
themselves than those ordinarily encountered in daily
life or during the performance of routine physical or
psychological examination or tests.”
[Federal regulations. 45 CFR 46. 102 (i)]
Definition of Minimal Risk
Ethics Board & Submission_Online_Handouts_Apr2020 8
Developing Clinical Research Professionals for the Nation
Category 1 Clinical research study of drugs where an investigational
new drug application is not required, or
Clinical research study of medical device where an
investigational device exemption application is not required
or the medical device is cleared / approved for marketing
and the medical device is being used in accordance with its
cleared / approved labelling.
Category 2 Collection of blood samples by finger stick, heel stick, ear
stick, or venipuncture
Category 3 Prospective collection of biological specimens for research
purposes by non-invasive means
Category 4 Collection of data through non-invasive procedures (not
involving general anaesthesia or sedation) routinely
employed in clinical practice, excluding procedures
involving x-rays or microwaves.
Expedited Review Categories
Developing Clinical Research Professionals for the Nation
Category 5 Research involving materials (data, documents, records, or
specimens) that have been collected, or will be collected
solely for non-research purposes
Category 6 Collection of data from voice, video, digital, or image
recordings made for research purposes.
Category 7 Research on individual or group characteristics or behaviour
(including, but not limited to, research on perception,
cognition, motivation, identity, language, communication,
cultural beliefs or practices, and social behaviour) or
research employing survey, interview, oral history, focus
group, program evaluation, human factors evaluation, or
quality assurance methodologies.
Expedited Review Categories
Ethics Board & Submission_Online_Handouts_Apr2020 9
Developing Clinical Research Professionals for the Nation
Examples of Research Studies
which may qualify for Expedited Review
• Collection of blood samples by venipuncture
• Review of patient’s medical records (with identifiers)
• Collection of biological samples by non invasive means
(e.g. urine, sputum, hair)
• Collection of data through routinely employed non-invasive
procedures (e.g. ultrasound, MRI), excluding procedures
that involve x-rays or microwaves
• Surveys & Interviews (non-anonymous)
Developing Clinical Research Professionals for the Nation
No more than Minimal Risk Greater than Minimal Risk
ECG Electromyography
MRI (without sedation) MRI, IV contrasting agent
Moderate exercise Max treadmill test
Urine collection via fresh catch Urinary catheter
Blood sampling of 3ml/kg/8 week Indwelling IV catheter
Ultrasound Skin biopsy
Routine diagnostic X-ray PET scan; CT scan
Standard psychological testing Extensive psychological testing
*Repetitive procedures and vulnerability may increase risk
Procedures of Minimal Risk
Ethics Board & Submission_Online_Handouts_Apr2020 10
Developing Clinical Research Professionals for the Nation
Example of studies:
• Clinical Trials (e.g. drug / device) evaluating the safety
and efficacy of the investigational drug/device
• Studies that involve invasive procedures
• High risk studies that evaluate new exercise programme
for elderly (for DSRB Domain F)
• All other applications that do not qualify the Exempt or
Expedited criteria
Full Board Review (FBR) (More than Minimal Risk)
Developing Clinical Research Professionals for the Nation
• Studies which require FBR are reviewed at a monthly
domain meeting. A quorum composed of the following
members is present:
o At least 5 members,
o At least 1 member whose primary area of interest is in
a non-scientific area,
o At least 1 member who is independent of the
institution or trial site.
• Only IRB members, who are independent of the
investigator and the sponsor of the clinical trial, will vote
or provide opinion for the review of the trial.
Who conducts Full Board Review (FBR)?
Ethics Board & Submission_Online_Handouts_Apr2020 11
Developing Clinical Research Professionals for the Nation
The FBR board can consist of:
1. Chairman (Scientific)
2. Deputy Chairman (Scientific)
3. Member (Scientific - relevant to Domain)
4. Member (Paraclinical- relevant to Domain)
5. Member (Non-Scientific Layperson – Legal)
6. Member (Non-Scientific Layperson –
Community/Subject advocate)
Example of IRB Board Composition
Developing Clinical Research Professionals for the Nation
Overview of Application Process
Application received by IRB
PI submits IRB application on iSHaRe / ROAM
IRB Secretariat requests for missing documents
& seek clarification
PI / CRC provides missing documents & answer queries
Application ready for IRB Review
Few rounds of
review by the
IRB
secretariat if
responses are
unsatisfactory
Ap
pli
ca
tio
n Application endorsed by Institution Representative (IR)
CRC (with help of CRA) drafts IRB application
Application endorsed by Department Representative (DR)
IRB will only
receive the
application
AFTER DRs
and IRs from all
sites have
endorsed the
application.
Ethics Board & Submission_Online_Handouts_Apr2020 12
Developing Clinical Research Professionals for the Nation
Application ready for IRB Review
Appeal
Process
Exempted
Conditionally
Approved,Until queries are
answered by PI
Re-Tabled for discussion
after PI answer
queriesNot Approved,
Tabled for Full
Board Review for
further discussion
Re
vie
wO
utc
om
e
Expedited
Review
Exemption
Review
Full Board Review (FBR)
Not
Exempted
Approved Approved Not
Approved
Non- Exemption Review
Overview of Application Process
Developing Clinical Research Professionals for the Nation
CIRB
• Submission deadline is the first working day of that same month.
DSRB
• Submission deadline is on the 15th day of the month or the next
earliest working day if that day falls on a weekend.
• With the exception of Biomedical Domain B1 whereby the submission
deadline is on the 1st working day of the month or the next earliest
working day if that day falls on a weekend.
PI should submit new applications with sufficient lead time for the
Department Representative and Institutional Representative to
endorse prior to the submission deadline.
Any submission after the deadline will be reviewed at the next full board
meeting.
Timeline for Submitting IRB Application(For Full Board Review)
Ethics Board & Submission_Online_Handouts_Apr2020 13
Developing Clinical Research Professionals for the Nation
NHG and Partner Institutions
• Submit DSRB application
through Research Online
Administration and Management
system (ROAM)
https://www.research.nhg.com.sg/sop/p
rocess/ROMP/Admin_Intranet_Login
SingHealth and Partner
Institutions
• Submit e-CIRB application
through Integrated System in
Healthcare for Research
(iShaRe)
https://ishare.singhealth.com.sg/
Where do you submit the IRB Application?
Developing Clinical Research Professionals for the Nation
Documents required for IRB Application
1. Completed e-CIRB / ROAM application form
2. Study Protocol
3. Qualifications and training certificates of Study team members
(Example: CVs, CITI and GCP certificates)
4. Informed Consent Form (or application for waiver of consent)
5. Questionnaires, Surveys and other tools to be used in the study
6. Information about the funding of the study
7. Investigator's Brochure and other safety information
8. Recruitment material / Advertisements of the study
9. Publications related to the study
10. Payment to subjects & Payment Schedule
**Ensure all documents have version number and version date
Ethics Board & Submission_Online_Handouts_Apr2020 14
Developing Clinical Research Professionals for the Nation
Other documents may also be required:
1. Data Collection Forms
2. Financial Disclosure Statement
3. Clinical Trial Agreement
4. Letters from other IRBs stating the study failed to obtain
approval previously
5. Translated Informed Consent Document and Translation
Certificates
6. Other documents that the IRB requests
7. Other documents to be provided to subjects
8. IRB review fee (cheque) and cover sheet (only applicable to
industry-sponsored studies)
**It is recommend to collate documents for submission dossier first,
in order to aid completion of IRB application form
Developing Clinical Research Professionals for the Nation
Research Studies must fulfil the following criteria:
• Risk to subjects are minimized and reasonable in relation to
anticipated benefits
• Reasonable selection of subject pool
• Informed consent will be obtained and documented
• Adequate provision for data monitoring to ensure safety,
protection of privacy of subjects and confidentiality of data
collected
• Additional protection for vulnerable subjects
Criteria for IRB Approval
Ethics Board & Submission_Online_Handouts_Apr2020 15
Developing Clinical Research Professionals for the Nation
Resources for IRB Application Process
CIRB Website
https://research.singhealth.com.sg/Pages/CentralisedInstitutionalR
eviewBoard.aspx
DSRB Investigator Manual
https://www.research.nhg.com.sg/wps/wcm/connect/romp/nhgrom
p/07+resources/nhg+investigator+manual
Developing Clinical Research Professionals for the Nation
Outcome of IRB FBR Review
• Types of review outcome:
o Approved
o Conditionally approved
o Re-tabled
o Not approved
• Review outcome by one board/domain is recognized by all
boards/domains
Ethics Board & Submission_Online_Handouts_Apr2020 16
Developing Clinical Research Professionals for the Nation
Approved
o Application was approved as submitted
o No changes are required for submitted documents
o Outcome is valid for 1 year from the date of approval
(refer to the approval letter for the validity date of
approval)
Outcome of IRB FBR Review
Developing Clinical Research Professionals for the Nation
Conditionally Approved
o No major issue
o PI is required to provide clarification or make minor
amendments to the application and/or submitted
documents
o PI’s response will be reviewed through expedited review
o Study will be approved once all issues have been
addressed
o Final outcome is valid for 1 year
Outcome of IRB FBR Review
Ethics Board & Submission_Online_Handouts_Apr2020 17
Developing Clinical Research Professionals for the Nation
Re-tabled for next review meeting
o Significant questions were raised and required further
information from PI or substantial modifications to the
proposal
o PI may be invited for the subsequent meeting
o Independent Consultant may be required to further
evaluate the proposal
o Application will be tabled for the next Full Board
meeting once additional information/amendments has
been obtained
Outcome of IRB FBR Review
Developing Clinical Research Professionals for the Nation
Not Approved
o Does not meet one or more criteria for approval
o Disapproval can only be made through majority vote
during the review meeting and not through expedited
review
o PI may request for appeal by writing in to the IRB
Outcome of IRB FBR Review
Ethics Board & Submission_Online_Handouts_Apr2020 18
Developing Clinical Research Professionals for the Nation
Key Takeaways
• Clinical Trials require IRB Full Board Review.
• Be familiar with the overview of IRB initial application process in
order to plan for and achieve smooth study startup.
• Collate documents for submission dossier to aid in completion of
IRB application form.
• Always refer to IRB website for latest versions of reference
documents and announcements.
Developing Clinical Research Professionals for the Nation
References
• NHG Investigator Manual 3rd Edition, October 2017
• CIRB
https://research.singhealth.com.sg/Pages/CentralisedInstitutionalReviewBoard.aspx
• DSRB
https://www.research.nhg.com.sg
Thank you for Completing the
Ethics Board & Submission Online Learning!
Ethics Board & Submission_Online_Handouts_Apr2020 19
Developing Clinical Research Professionals for the Nation
Join us at the CRC Level 1 Programme
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certificate
NOW!
More information on CRC Level 1 Programme
is available at:
https://www.scri.edu.sg/clinical-research-
coordinator-level-1-programme/
For enquires, please contact
Gain a more comprehensive introduction to the operations of clinical
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Topics Covered
• Overview and Protocol
• Disease and Investigations
• Essentials in Clinical Practice
• Start-up Activities
• Ethics and Study Visits
• Informed Consent
• Site File and Monitoring
• CT Regulations and Safety
• Investigational Product
• Laboratory and Study Supplies
• Study Closure
Developing Clinical Research Professionals for the Nation
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