Research Toolkits | SingHealth Duke-NUS

1. Pre-Study Activities

The pre-study phase encompasses activities required to ensure the study is ready for participant recruitment. This includes obtaining approvals from the Institutional Review Board (IRB) and HSA or MOH (where applicable), as well as establishing study infrastructure by preparing the study site(s), study team(s), and availability of essential documents and systems.

At least 2 months should be allocated for pre-study activities. For restricted Human Biomedical Research (rHBR) or clinical trials where further regulatory approvals are involved, the preparation timeline will be longer. It is important to consider the pre-study processes involved carefully. Inadequate preparation can lead to delays, compliance issues, and potential risks to participant safety. Multi-site considerations for a HBR/Clinical Trial

→ Study Agreements and Contracts

Key agreements such as the Clinical Trial Agreement (CTA), or the Research Collaborative Agreement (RCA), outlines the study scope, budget, payment terms, indemnity, insurance and confidentiality obligations. The negotiation and execution of agreements can be time-consuming and may significantly impact study start-up timelines. As such, early engagement with institutional research offices is essential to facilitate timely review and agreement execution.

→ Considerations for a HBR/Clinical Trial Involving Multiple Sites

For HBR, a multi-Research Institutions (RI) HBR involves the implementation of the same research protocol at 2 or more independent investigational sites [under different RI]. The Lead RI is responsible for the coordination of the common HBR conducted in a multi-RI research.
For cross cluster HBR, the individual RI will still be responsible for the supervision and control of the HBR conducted under its auspices, such as the duties of reporting serious adverse events, suspected offences or contraventions.
For Investigator-initiated clinical Trials (IIT), multiple sponsors (i.e. each institution sponsoring for their own trial sites) for a single protocol are allowed but a lead sponsor will have to be nominated.
For a non-SingHealth institution that wishes to appoint SingHealth as the Research Institution under the regulation of HBRA, the SingHealth Institution involved in the collaboration to contact oric@singhealth.com.sg

Reference:

Oversight Workflow for a Multi-RI Human Biomedical Research (HBR) (Intranet Only)

SingHealth RI Site Qualification Visit Workflow for Non-SingHealth Site (Intranet Only)

HSA Guidance on Multi-sponsor Investigator Initiated Trials

→ IRB and Regulatory (HSA/MOH) Submission and Approval

The research study must be submitted for IRB approval and HSA/MOH approval (where applicable). Approval must be obtained prior to initiation of the research.
For Medical Device studies, a Clinical Research Material (CRM) notification to HSA may be required.

Reference:

Submissions to CIRB: SHS-RSH-CIRB-206 (Intranet Only)

HSA Guidance on Regulatory Requirements for New Applications and Subsequent Submissions

Application of Restricted Human Biomedical Research to MOH: SHS-RSH-ORIC-315 (Intranet Only)

HSA Guidance on Clinical Research Materials

→ Finalisation of Essential Study Documents

Essential study documents such as the study protocol and the informed consent form needs to be customized accurately before submission to the IRB/regulatory authorities for approval.
The informed consent form must accurately describe the study protocol, study procedures and information/explanations according to the essential elements (eg. HBRA section 12 or ICH-GCP 4.8.10 – (a) to (t)). It should contain a unique version footer <Insert Version No - Version Date>.
Information across all essential documents should be consistent. Any change in one document should be appropriately reflected in the other documents as well.
The study protocol should consider the level of safety monitoring and if a Data Safety Monitoring Board is required.

Reference:

Informed Consent Requirements: SHS-RSH-CIRB-219 (Intranet Only)

Data Safety Monitoring Board: SHS-RSH-ORIC-CWP-205 (Intranet Only)

Waiver of Consent - Definition of Greater Public Good

→ Incidental Findings

For a HBR, it is important to establish an Incidental Findings Management Plan for the research. Participants will be asked during the informed consent process to indicate on the informed consent form whether they wish to be notified in the event of an incidental finding. The participant has a choice to indicate "Yes" or "No" on the informed consent form.
Where there are no plans to inform the participant of incidental findings, this information must also be stated in the informed consent form and discussed during the informed consent discussion.

Reference:

Management of Incidental Findings: SHS-RSH-ORIC-CWP-203 (Intranet Only)

→ Tissue Banking Activities

Investigators should determine if the study is a Research Tissue Banking protocol. A Research Tissue Banking protocol is required to be regulated under Human Tissue Framework (HTF).
For setting up of Research Tissue Bank, refer to this link.

2. Study Initiation

A research study can only be initiated after the following are in place:

IRB approval
Regulatory approval (e.g. HSA, MOH – where applicable)
Fully executed agreement(s)/contract(s) by all parties
Study protocol approved by IRB and HSA/MOH (if applicable)
Informed Consent Form approved by IRB and HSA/MOH (if applicable)
Study logistics (e.g. study drugs/medical device, laboratory supplies, etc.) and manpower availability

A Site Initiation Visit (SIV) should then be planned by the study team prior to study recruitment. Additionally, an Investigator Site File (ISF) should be established to store all study-related documents and communications. The Office of Research, Integrity and Compliance (ORIC) has developed a package to assist researchers in the set-up of an ISF. Included in the package are templates and tools to help researchers in record-keeping. Please click here to find out more.

Reference:

Conduct of Site Initiation for Research: SHS-RSH-CTCC-CWP-202 (Intranet Only)

3. Study Conduct

It is imperative that the conduct of research is carried out in accordance with the approval protocol, ethical standards, and regulatory requirements. Proper conduct safeguards participant safety, ensures data integrity, and minimises non-compliance. All study team members must be appropriately trained, delegated, and documented before performing any study-related activities.

→ Study Delegation

To support oversight by the PI, a site-specific delegation log should be maintained to document the delegation of tasks.
Delegation logs must include only study team members who are formally appointed, appropriately trained and authorised for that site.

→ Study Specific Training

The PI is responsible for ensuring that all study team members are adequately trained on the protocol and study procedures. Evidence of training prior to performance of study tasks should be documented.

→ Informed Consent Process

Informed consent must be obtained from the participant/legal representative before any study activities are performed. Administration of questionnaires is also considered as a study activity.
Use only the latest IRB/HSA-approved consent form.Verify the version and date against the IRB/HSA approval letter(s) prior to use. The use of unapproved or superseded versions is considered as a non-compliance.
Ensure that the informed consent form is personally signed and dated by all required parties.
Document the informed consent process and study participation in the participant's medical records.
Ensure only authorised and IRB approved study team members are delegated to conduct the informed consent process.
Where applicable, ensure that the witness present understands the language in which the informed consent process is conducted in.

Reference:

Process of Obtaining Informed Consent: SHS-RSH-CTCC-CWP-203 (Intranet Only)

Guidance on Remote Consent Process and Documentation for Research (Intranet Only)

→ Safety Reporting & Non-Compliances

All safety events and non-compliances (e.g. Serious Adverse Events (SAEs), protocol deviations or non-compliances) must be reported to the IRB and regulatory authorities (where applicable) within the required timelines.

Reference:

Reporting of Serious Adverse Event: SHS-RSH-CIRB-232 (Intranet Only)

Reporting of Serious Adverse Events to Ministry of Health: SHS-RSH-ORIC-313 (Intranet Only)

Handling Non-Compliance: SHS-RSH-CIRB-228 (Intranet Only)

Reporting of Suspected Offence or Contravention from Human Biomedical Research to Ministry of Health: SHS-RSH-ORIC-312 (Intranet Only)

Infographic - Reporting Workflow for Protocol Deviation and Non-compliance in Clinical Research

→ Data Management & Data Breach

Source data are information in original records and certified copies of original records of clinical findings, observations, or other activities necessary for the reconstruction and evaluation of the study.
All data collected in a research study should have a corresponding source documentation and be maintained to ensure accuracy, completeness, and traceability.
Research data should be collected on a Case Report Form (CRF). The CRF can be in hard copy or in the form of an Electronic Data Capture (EDC) system (e.g. REDCap), using approved and secure data management processes.
For HBR or clinical trials, research data should be disseminated in de-identified form by masking or removing identifiers, while separately and securely maintaining the record linkage key by the PI.
Appropriate safeguards should be in place to protect participant confidentiality, restrict authorised access and support secure storage and handling of research data.
Any research data breach should be managed in accordance with SingHealth’s Data Breach policy. Such events constitute as a non-compliance and require prompt reporting to the Institution’s Research Office, IRB, and ORIC.

Reference:

Management of Source Data and Source Documents in Research: SHS-RSH-CTCC-CWP-204 (Intranet Only)

SingHealth Cluster Research Data Management Policy – Clinical Trial and Clinical Research Data: SHS-MI-R-204 (Intranet Only)

Interim Guidelines for De-identification of Dataset under Human Biomedical Research Act (HBRA): SHS-RSH-HSRC-CWP-202 (Intranet Only)

SingHealth Cluster Research Data Management Policy – Managing Genomic or Nucleic Acid Data Held for Open Access: SHS-MI-R-202 (Intranet Only)

SingHealth Data Breach Management Policy: SHS-GOPS-DPO-202 (Intranet Only)

Policy on the use of FormSG (Intranet Only)

→ Monitoring, Audits and Inspections

Studies may be subjected to monitoring by SingHealth ORIC/authorized parties, audits, or regulatory inspections (e.g. MOH/HSA). These may occur at any time during the study. For audits and inspections, these may even occur after study closure.
Access to all study data (including archived documents) during monitoring, audit and inspection is required.

Reference:

Preparing and Conducting Monitoring Visit: SHS-RSH-ORIC-311 (Intranet Only)

Preparation for Sponsor Audits and Regulatory Authority Inspection for Research: SHS-RSH-CTCC-CWP-205 (Intranet Only)

Research Audit Framework: SHS-RSH-ORIC-301 (Intranet Only)

4. Study Closure

Study closure should only be initiated when all study-related activities, including data collection and follow-up, have been completed.
The PI is required to provide a study closure report to the IRB. Once the study is closed, no further data collection will be allowed.
For clinical trials, the archival duration is at least 15 years or as agreed with the sponsor.
For HBR and other research, data should be archived for a minimum of 6 years after completion of the research study

5. PI Self-Assessment Form (PISAF)

The PISAF is a self-assessment tool to be completed by all PIs involved in research conducted in SingHealth. The PI will self-assess for each of their research study on the extent of compliance in accordance with required law, regulations and institution policies.

Other Resources

Resources/Documents	Descriptions
Legislation-Statutory Acts and Applicable Regulations	Legislation-Statutory Acts and Applicable Regulations
International Compilation of Human Research Standards (2020 edition)	International Compilation of Human Research Standards
International Conference for Harmonisation E6 (R3) Guidelines for Good Clinical Practice (ICH E6 (R3) GCP)	International ethical and scientific quality standards for designing, conducting, recording and reporting trials that involve human participants.
Human Biomedical Research Act, Regulations, Guidance and FAQ	Human Biomedical Research Act, Regulations, Guidance and FAQ
Health Sciences Authority (HSA)	This website provides information on the regulatory requirements and applications for conducting clinical trials in Singapore.