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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_Online_Handouts_Apr2020 2
Developing Clinical Research Professionals for the Nation
• 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
Developing Clinical Research Professionals for the Nation
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.
Research team_Online_Handouts_Apr2020 3
Developing Clinical Research Professionals for the Nation
Principal Investigator (PI)
Developing Clinical Research Professionals for the Nation
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)
Research team_Online_Handouts_Apr2020 4
Developing Clinical Research Professionals for the Nation
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
Developing Clinical Research Professionals for the Nation
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.
Principal Investigator
Research team_Online_Handouts_Apr2020 5
Developing Clinical Research Professionals for the Nation
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)
Principal Investigator
Developing Clinical Research Professionals for the Nation
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
Principal Investigator
Research team_Online_Handouts_Apr2020 6
Developing Clinical Research Professionals for the Nation
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.
Developing Clinical Research Professionals for the Nation
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
Research team_Online_Handouts_Apr2020 7
Developing Clinical Research Professionals for the Nation
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.
Responsibilities of PI
Developing Clinical Research Professionals for the Nation
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
Responsibilities of PI
Research team_Online_Handouts_Apr2020 8
Developing Clinical Research Professionals for the Nation
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.
Responsibilities of PI
Developing Clinical Research Professionals for the Nation
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
Responsibilities of PI
Initial
Amendment
Research team_Online_Handouts_Apr2020 9
Developing Clinical Research Professionals for the Nation
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
Responsibilities of PI
logistical / administrative
immediate hazard(s)
Developing Clinical Research Professionals for the Nation
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
Responsibilities of PI
Research team_Online_Handouts_Apr2020 10
Developing Clinical Research Professionals for the Nation
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)
Responsibilities of PI
randomization
Developing Clinical Research Professionals for the Nation
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
Responsibilities of PI
Research team_Online_Handouts_Apr2020 11
Developing Clinical Research Professionals for the Nation
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.
Responsibilities of PI
Developing Clinical Research Professionals for the Nation
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.
Responsibilities of PI
Research team_Online_Handouts_Apr2020 12
Developing Clinical Research Professionals for the Nation
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.
Responsibilities of PI
Developing Clinical Research Professionals for the Nation
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).
Responsibilities of PI
Research team_Online_Handouts_Apr2020 13
Developing Clinical Research Professionals for the Nation
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
Responsibilities of PI
Developing Clinical Research Professionals for the Nation
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.
Research team_Online_Handouts_Apr2020 14
Developing Clinical Research Professionals for the Nation
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
Developing Clinical Research Professionals for the Nation
CRC’s Role & Responsibilities
Research team_Online_Handouts_Apr2020 15
Developing Clinical Research Professionals for the Nation
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
Developing Clinical Research Professionals for the Nation
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
Research team_Online_Handouts_Apr2020 16
Developing Clinical Research Professionals for the Nation
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.
Developing Clinical Research Professionals for the Nation
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
Change / Addition of PI
Research team_Online_Handouts_Apr2020 17
Developing Clinical Research Professionals for the Nation
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
Change / Addition of PI
Developing Clinical Research Professionals for the Nation
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
Research team_Online_Handouts_Apr2020 18
Developing Clinical Research Professionals for the Nation
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
Developing Clinical Research Professionals for the Nation
Study Site Team Communication
Research team_Online_Handouts_Apr2020 19
Developing Clinical Research Professionals for the Nation
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
Developing Clinical Research Professionals for the Nation
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
Research team_Online_Handouts_Apr2020 20
Developing Clinical Research Professionals for the Nation
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
Developing Clinical Research Professionals for the Nation
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!
Research team_Online_Handouts_Apr2020 21
Developing Clinical Research Professionals for the Nation
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
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
Developing Clinical Research Professionals for the Nation
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