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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.



• Introduction to Institutional Review Board (IRB)

• Types of IRB in Singapore - CIRB vs DSRB

• Types of IRB review and outcome

Module Outline


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



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?


2 Major IRBs in SingaporeReviewing Clinical Research Studies

SingHealth

Centralised Institutional

Review Board

(CIRB)

National Healthcare Group

Domain Specific Review Board

(DSRB)



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)


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



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.


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.



• 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


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.



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


“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



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


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



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)


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



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)


• 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)?



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


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.



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


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)



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?


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

https://www.research.nhg.com.sg/sop/process/ROMP/Admin_Intranet_Login

https://ishare.singhealth.com.sg/



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


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



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


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

https://research.singhealth.com.sg/Pages/CentralisedInstitutionalReviewBoard.aspx

https://www.research.nhg.com.sg/wps/wcm/connect/romp/nhgromp/07+resources/nhg+investigator+manual



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)



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




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



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




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.


References

• NHG Investigator Manual 3rd Edition, October 2017

• CIRB


• DSRB

https://www.research.nhg.com.sg

Thank you for Completing the

Ethics Board & Submission Online Learning!


https://www.research.nhg.com.sg/



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Topics Covered

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• Ethics and Study Visits

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