Research team Online Handouts Apr2020 - SCRI · ^1 CITI: Collaborative Institutional Training Initiative • NHG requires CITI Investigator’s Course • SingHealth requires CITI

Research team_Online_Handouts_Apr2020 1

RESEARCH TEAM

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.



• Research Team at Trial Site

• Principal Investigator

• Clinical Research Coordinator

• Signature / Responsibility Log

• Training Log

• Change / Addition of PI and Study Team Members

• Study Site Team Communication

Module Outline


Principal

Investigator (PI)

Co-investigators Collaborator Other Members

• Primarily

responsible for

the conduct of

the study

• Leader

• Perform critical

study-related

activities and/or;

• Make important

decisions on

study-related

matters

• E.g. Medical

residents,

Associates

• Assist with study-

related activities

that do not

involve subject

contact

• E.g. scientists,

research fellows,

data analyst

• Clinical

Research

Coordinator

• Study Nurse

• Pharmacist

• Research

Manager

Research Team at Trial Site

Study Team Members

• Any personnel responsible for conducting the trial, obtaining informed

consent, collecting of data or reporting of study information.



Principal Investigator (PI)


Who Can Be A PI?

Qualifications

– Qualified by education, training and experience to assume

the responsibility for the proper conduct of a research study.

Supporting documents required:

1. Curriculum Vitae

2. Research Training Records

3. Medical Qualifications (required by regulatory

authorities)



1. Curriculum vitae (CV)

– CIRB: Updated within the past 2 years

– DSRB: Updated within past 1 year

– Information to be included in CV:

• That he/she is currently a staff of the respective

institution where the research will be conducted

• Strongly encourage PI and research team NOT to

include personal data in the CV

• Any other relevant information required by your

Institution IRB

Principal Investigator


2. Minimal Requirement for Research Training

PI Institution ICH-GCP CITI^1 FCOI^2

Clinical trials

DSRB: NHG, NUHS &

Partner InstitutionsYes No Yes

CIRB: SingHealth &

Partner InstitutionsYes Yes No

Research

studies other

than clinical

trials

DSRB: NHG, NUHS &

Partner InstitutionsNo Yes Yes

CIRB: SingHealth &

Partner Institutions No Yes No

^1 CITI: Collaborative Institutional Training Initiative

• NHG requires CITI Investigator’s Course

• SingHealth requires CITI Biomedical Research Investigators and Key Personnel

^2 FCOI: Financial Conflicts of Interest Course (sub-component of CITI Program)

* Above information were updated as of 22 April 2020. Please refer to your institution IRB for the

latest information.




2. Minimal Requirement for Research Training

• NHG Human Biomedical Research

Essential Research Conduct (HBR ERC)

Course:

o Applicable to all NHG institution staff

involved in studies regulated by the

Human Research Biomedical Research

Act

o Please visit NHG website for more

details on the requirements: https://www.research.nhg.com.sg/wps/wcm/connect/romp/n

hgromp/06+conducting+research/hbr+essential+research+c

onduct+course

• SingHealth Human Biomedical Research

Act (HBRA Training)



3. Medical Qualifications required by regulatory

authorities

Under the Health Products (Clinical Trials) and Medicines (Clinical

Trials) Regulations, a qualified practitioner refers to:

• A registered medical practitioner under the Medical

Registration Act (Cap. 174); or

• A registered dentist under the Dental Registration Act (Cap.

76) whose name appears in the first division of the Register of

Dentists maintained and kept under section 13(1)(a) of that Act.

Medical: https://prs.moh.gov.sg/prs/internet/profSearch/main.action?hpe=SMC

Dental: https://prs.moh.gov.sg/prs/internet/profSearch/main.action?hpe=SDC


https://imsva91-ctp.trendmicro.com/wis/clicktime/v1/query?url=https://www.research.nhg.com.sg/wps/wcm/connect/romp/nhgromp/06%2bconducting%2bresearch/hbr%2bessential%2bresearch%2bconduct%2bcourse&umid=876E3D51-A4F6-B705-8624-F1C0238DC813&auth=6e3fe59570831a389716849e93b5d483c90c3fe4-131b66ea6996b112d16983e005fcc34493492132



Special Considerations

If PI is a Visiting Consultant

If it is a multi-centre study

involving SingHealth and

NHG Institutions

If it is a multi-centre study

within 1 cluster

• Study team should have at

least one full time staff

within the institution

• Approved by institution

to be a PI

Which IRB to submit the

research applications?

Depends on the overall PI’s

cluster (CIRB or DSRB).

Who is the overall PI?

• For commercially-

sponsored trials, the

overall PI is usually

appointed by the sponsor.

• For investigator-initiated

trials, the person who

initiated the trial will be the

overall PI.

• PI for one of the sites will

be the overall PI and the

primary contact person

liaising with the IRB.

• Remaining PIs may be

appointed as the Site-PI

who is responsible for the

conduct of the study in

his/her institution.


Responsibilities of PI

1. Qualifications and Agreements

2. Adequate resources

3. Medical Care of Trial Subjects

4. Communication with IRB/IEC

5. Compliance with Protocol

6. Investigational Product (IP)

7. Randomization Procedures and Unblinding

8. Informed Consent of Trial Subjects

9. Records and Reports

10. Progress Report

11. Safety Reporting

12. Premature Termination or Suspension of a Trial

13. Final Report(s) by Investigator



1. Fulfill the qualifications and agreements

• Qualified by education, training and experience to assume

responsibility for proper conduct of the trial,

• Familiar with the appropriate use of the investigational

product,

• Comply by GCP and applicable regulatory requirements,

• Permit monitoring and auditing by the sponsor,

• Maintain a delegation log of qualified team members.



2. Secure adequate resources

• Demonstrate the potential to achieve the recruitment target

within the agreed timeframe

• Have sufficient time to properly conduct and complete the trial

• Have sufficient qualified staff and adequate facilities

• Ensure study team members are adequately informed of the

protocol, investigational product and duties.

• Supervising study team




3. Medical Care of Trial Subjects

• Responsible for all trial-related medical decisions

• Ensure adequate medical care is provided to the subject for

any trial-related adverse events, including clinically significant

laboratory values, related to the trial.

• To ascertain the reasons of premature withdrawal from

the study while respecting the subject's rights.



4. Communication with IRB

• To obtain IRB written approval prior study initiation:

o Protocol

o Written informed consent form

o Consent form updates

o Subject recruitment procedures (e.g., advertisements)

o Any other written information to be provided to subjects

• To provide an updated copy to IRB:

o Investigator’s Brochure


Initial

Amendment



5. Compliance with Protocol

• Conduct the trial in compliance with the protocol

• Sign the protocol or an alternative contract to confirm the

agreement

• Should not implement any deviation/changes to the

protocol without the sponsor’s agreement and IRB approval

except if:

o Only involves logistical or administrative aspects of the trial,

o To eliminate an immediate hazard(s) to trial subjects. The

implemented deviation/changes should be submitted to the IRB,

sponsor and regulatory authority as soon as possible.

• Document and explain any protocol deviation


logistical / administrative

immediate hazard(s)


6. Investigational Product (IP)

• Maintain IP Accountability Records

• Ensure proper storage as specified by the sponsor and in

accordance with applicable regulatory requirements

• Ensure proper usage in accordance with the approved protocol

• Explain the correct usage of the IP to each subject

• The PI may delegate some or all of the IP accountability duties

to an appropriate pharmacist or study team member under

the PI’s supervision




7. Randomization Procedures and Unblinding

• Follow the trial's randomization procedures

• Ensure the code is broken only in accordance with the

protocol

• Any premature unblinding should be promptly

documented and explained to the sponsor (e.g. accidental

unblinding, unblinding due to a serious adverse event)


randomization


8. Informed Consent of Trial Subjects

• Comply with GCP, regulatory and IRB requirements when

obtaining and documenting informed consent

• Should not coerce or unduly influence the subject to

participate or continue in the trial

• Provide ample time and opportunity for the subject to enquire

about the trial and to decide whether to participate




9. Records and Reports

• Maintain adequate and accurate source documents and

trial records. Source Doc should be attributable, legible,

contemporaneous, original, accurate and complete.

• Ensure accuracy, completeness, legibility and timeliness

of data reported to sponsor in CRFs and reports.

• Data reported on the CRFs should be consistent with the

source documents.

• Amendments should be traceable (initiated, dated,

explained if necessary) and should not obscure the original

entry (i.e., an audit trail should be maintained).

• Maintain Essential Documents.



10.Progress Report

• Submit written summaries of the trial status to the IRB

annually or more frequently as requested.

• Provide written reports promptly to the sponsor, IRB and

institution on any changes that are:

o Affecting conduct of the trial, or

o Increase risk to the subjects.




11. Safety Reporting

• Report all serious adverse events (SAEs) immediately to

the sponsor, unless specified as not needing immediate

reporting in the protocol or other study documents.

• Detailed written reports should be submitted promptly

afterwards.

• For death cases, provide additional requested information (eg,

autopsy reports and terminal medical reports) to the sponsor

and IRB.



12.Premature Termination or Suspension of a Trial

• Inform regulatory authority and institution.

• Inform trial subjects and assure appropriate therapy and

follow-up are provided.

• Provide a detailed written explanation of the termination or

suspension to the sponsor (if PI/IRB terminates the trial)

and/or IRB (if PI/sponsor terminates the trial).




13.Final Report(s) by Investigator

• Inform the institution

• Provide a summary of the trial outcome to IRB

• Provide any reports required by the regulatory authority

• Provide all required reports to sponsor



Clinical Trial & Non-Clinical Trial Studies

Study Roles Institution ICH-GCP CITI FCOI

Co-Investigator

DSRB: NHG, NUHS &

Partner InstitutionsNo Yes Yes

CIRB: SingHealth &

Partner Institutions No Yes No^

Other study

team members

DSRB: NHG, NUHS &

Partner InstitutionsNo No Yes^

CIRB: SingHealth &

Partner Institutions No Yes No^

^For cross cluster studies. If study team member from SingHealth or its partner institutions is involved in the

design, conduct or reporting of research conducted in NHG or its partner institutions, he/she will require to

complete the NHG FCOI training.

An updated SIGNED & DATED CV (no personal data) of all study

team members should be filed in the Investigator Site File.

Training of Other Study Team Members

* Above information were updated as of 22 April 2020. Please refer to your institution IRB for

the latest information.



Clinical Research Coordinator (CRC)

A specialized research professional who

conducts most of the essential study duties at

the clinical research site under the immediate

direction of a PI.

1. In-depth knowledge of GCP, regulatory requirements and protocol

2. Primarily responsible for managing all aspects of the trial.

For example, trial management, IP management, safety and trial

compliance


CRC’s Role & Responsibilities



Signature Sheet

To document the roles, responsibilities and signatures of all

site staff who have been authorised by PI to conduct trial-

related duties

Signature Sheet from HSA website


To document the training received by the study staff to

ensure they are adequately qualified by education, training

and experience to conduct trial-related procedures

Training Log

Training Log from HSA website



Change / Addition of PI

When to appoint a new PI?

– PI resigning from institution

– PI away for an extended duration (eg. maternity leave,

HMDP)

– The criteria to appoint a new PI are differ between the

institutions and the Regulatory Authority

• Check with your institution research office and the

regulatory authority website on the latest criteria.


What are the responsibilities of the new PI?

– Assume all responsibilities of PI for the conduct of the study

– Can only perform the study activities after obtaining approval

from IRB and HSA

What are the qualifications requirements?

– All the qualifications requirements of being a PI as specified

by his/her institutional IRB




What needs to be done?

Obtain approval from:

- Sponsor

- IRB

- HSA

- Grant Bodies

(if applicable)

Inform CRA

Approval obtained

Update study documents

Inform the team



When will there be a change / addition of study team member?

– Study team member leaving the study team / institution

– Study requires the expertise of the new study team member to

perform specific study-related duties

What are the new Study Team Member’s responsibilities?

– New study team member’s roles and responsibilities will be

delegated by the PI

– Can only perform his / her delegated duties after IRB approval

What are the qualifications requirements?

– PI will determine if the new study team member is adequately

qualified to perform the trial related duties

Change / Addition of Study Team Member

Ensure proper handover



What needs to be done after approval was obtained from IRB?

• Obtain the following documents from the new team member and file in

the ISF:

o Copy of signed and dated latest CV

o Relevant training documents (e.g. CITI, GCP certificate)

• Update Signature Sheet

o For staff leaving the study team: Indicate an end date (i.e date when

he/she formally ended his/her duty)

o Include the new study team member in the Signature Sheet with PI

delegated roles and responsibilities

• Update Training Log

o Include the new study team member’s training details

• Signed and dated CVs and GCP &/or CITI Cert

Update Study Documents


Study Site Team Communication



PI / Site PI is primarily responsible for all

communications regarding the trial.

However, CRC is more intimately involved with the

details of the study and usually involved in assisting PI

with the coordination of communication with the rest of

the study team members.

Communications with Study Team


ImportanceTo keep study team members informed of the study updates to

ensure conduct of study is always in compliance to the latest

protocol

Before trial

• Inform study team members about the research trial objective, protocol and

their respective delegated duties and functions

• Disseminate essential study information

During trial

• Update study team members on the study responses, protocol

amendments, deviations, adverse events, new information from sponsor,

specific problem areas

Completion / Termination of trial

• Inform study team members about study completion / termination



Key Takeaways

• Know your responsibilities and take ownership

• Being part of the study team

– Qualifications, training and delegation

• Communication with study team is key to successful

trial implementation


References

• ICH-GCP E6(R2)

• NHG Investigators’ Manual 3rd edition

• NHG Research and Development Office

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

• SingHealth CIRB https://research.singhealth.com.sg/Pages/CentralisedInstitutionalReviewBoard.aspx

• Health Sciences Authority Signature Sheet and Training Log

https://www.hsa.gov.sg/clinical-trials/conducting/template-forms

Thank you for Completing the

Research Team Online Learning!

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

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

https://www.hsa.gov.sg/clinical-trials/conducting/template-forms



Join us at the CRC Level 1 Programme

Get your

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

[email protected]

Gain a more comprehensive introduction to the operations of clinical

trial with practical hands-on training

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


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