Institutional Review Board

Guidelines

​​​​​​​​​​​​​​​​​​​​​​​ ​​​​​​​​​​​​1) General NTU-IRB Guidelines 
1.1 Cross-recognition of NTU-IRB and NHG DSRB ethics review
1.2 NTU-IRB Guidelines
1.3 Minimum Training Requirements

2) HBRA-Related Guidelines

Singapore has enacted the HBRA on 21 Aug 2015 to regulate human biomedical research and the handling of human tissues for use in research. For more information on MOH Guidelines on HBRA - please click here.

 2.1 Does your research fall within the scope of HBRA?
​ 2.2 Prohibition against trading of human tissues
 2.3 Prohibited and Restricted human biomedical research (rHBR)

​​​​ 3) Conduct of Research ​Guidelines

 3.1 Requirements of Witness for appropriate consent taking

 3.2 Requirement for consent for research involving Minors
 3.3 Information to be provided before taking appropriate consent
 3.4 Advertisements/ Notices for recruitment of research participants
 3.5 Guidelines for Advertisements/Recruitment Materials from External Institutions
 3.6 Incident Reporting                                                                                                                                     3.7 Incidental Findings (IFs)
 ​​​3.8 Continuing Reviews(CR)/Study Completion Review​

1) General NTU-IRB Guidelines​​​
 

1.1 Cross-recognition of NTU-IRB and NHG DSRB ethics review(updated 29 Jan 2018)

NTU-IRB and National Healthcare Group (NHG) DSRB have agreed to cooperate and enable cross-recognition of each other's ethics review, thereby eliminating dual reviews of the same research protocol. Collaborative studies involving both NTU and NHG investigators can be reviewed by either Party's IRB, and should be submitted by the Lead PI to their respective institution's IRB. If the collaborative research involves patients/medical/dental records or databases f​​rom NHG institutions, ethics review must be made through NHG DSRB.

NTU-PIs who have obtained DSRB approval are required to notify NTU-IRB by submitting your DSRB approval letter through NORA (choose "NHG DSRB Approved Project" option). NTU-IRB will issue a letter of notification stating that the application has been approved by NHG DSRB and no review is required by NTU-IRB based on the mutual recognition agreement. 

Please click here for a list of FAQs on this cross-recognition.

​1.2 NTU-IRB Guidelines

Exempted From Full IRB Review Expedited Review Full IRB Review
Exempt from Full IRB review form (Biomed/Non Biomed) NTU IRB Application form (Biomed/Non Biomed) NTU IRB Application form (Biomed/Non Biomed)
Review by secretariat and approved by Chair Review by Chair and a member of IRB with the expert domain Review by the Board which meets once a month

  • Vulnerable population (adapted from CITI)

    ·        Children have a wide range of capacity depending on age, maturity and psychological state. There is potential for control, coercion, undue influence, or manipulation by parents, guardians, or investigators, particularly of young children.

    ·        Embryos and Fetuses have absolutely no capacity and are under the direct control of the mother.

    ·        Mentally Disabled Individuals have problems with capacity, which may be continuous or fluctuating, depending on the disability. In addition, they may have limitations on voluntariness because often they are institutionalized or hospitalized, are economically and educationally disadvantaged, and suffer from chronic diseases. As a result, they are potentially subject to control, coercion, undue influence, or manipulation.

    ·        Emergency Situations create a situation where capacity and voluntariness is compromised. There are often limitations to capacity due to the emergency condition. There are often limitations on voluntariness due to time constraints or hospitalization. An example is research on heart attack medications, in which the subjects are asked to consent in the ambulance on the way to the hospital. There is potential for control, coercion, undue influence, or manipulation.

    ·        Hierarchical Social Structures that confront hospitalized patients, nursing home residents, students, prisoners, military personnel, and some ethnic groups create situations where voluntariness can be compromised. There is potential for control, coercion, undue influence, or manipulation.

    ·        Educationally Disadvantaged Subjects may have limitations on understanding of the study they will participate in, and may even be illiterate. The possibility exists for undue influence and/or manipulation.

    ·        Economically Disadvantaged Subjects may be vulnerable due to a limitation on voluntariness. They may enroll in research only to receive monetary compensation (such as in Phase I drug studies), or they may enroll in research to obtain medical care they cannot otherwise afford. There is potential for undue influence or manipulation.

    ·        Marginalized Social Groups may lack influence in society as a result of race, age, disease, or caste systems. These groups often do not have full access to social institutions such as the legal system. There is potential for control, coercion, undue influence, or manipulation.

    ·        Individuals with Incurable or Fatal Diseases often have limitations on voluntariness, and in addition may have problems with capacity caused by disease or medications. These individuals may accept very high risks in desperation for a cure. ​


 ​

​1.3 Minimum Training Requirements  (updated 1 Dec 2017)

​​There is a need for minimum standards in training requirements to ensure the proper and ethical conduct of research on human subjects. This is to enable investigators and study team members to apply these ethical principles in the design, conduct and reporting of your research. For NTU, we have partnered with the Collaborative Institutional Training Initiative (CITI) to offer the web-based training programme to cover various foundational topics on ethical research and human protection. 
Please click here to register for your account using your NTU (or affiliated) email address, and choose one track from the below to register for a course appropriate to your research work. 
Please note that CITI certification is required for all domains in NTU IRB, before the review of your ethics application can proceed.



    2) HBRA-Related Guidelines

    2.1​ Does your research fall within the scope of HBRA? (updated 1 Nov 2017)

    ​​​​​​

    2.2​ Prohibition against trading of human tissues (updated 1 Nov 2017)

     

    Effective 1 Jan 2017, HBRA prohibits commercial trading (i.e. buying and selling) of human tissue, as well as advertisements relating to such trading. This prohibition upholds the principle that human tissue should be obtained only through altruistic donations.

    This may affect you if you make use of human tissue in the course of your work. If you have previously made arrangements to obtain and/or supply human tissue, whether for use in therapy or research, please ensure that your arrangements are not in contravention of the prohibitions in the HBRA. Further information can be found on MOH's website. A guide is available here.

    2.3​ Prohibited and Restricted human biomedical research (rHBR) (updated 1 Nov 2017)

    Prohibited human biomedical research is defined in the Third Schedule of HBRA, and these include:

    1. Human biomedical research involving the development of human-animal combination embryos referred to in paragraph 2(a)(i) or (iii) of the Fourth Schedule beyond 14 days or the appearance of the primitive streak, whichever is the earlier.

    2. Human biomedical research involving the implantation of any human-animal combination embryo into the uterus of an animal or a human.

    3. Human biomedical research involving the introduction of human stem cells (including induced pluripotent stem cells) or human neural cells into the brain of living great apes whether prenatal or postnatal.

    4. Human biomedical research involving the breeding of animals which have had any kind of​ of pluripotent stem cells (including induced pluripotent stem cells) introduced into them.

    Restricted human biomedical research (rHBR) is defined in the Fourth Schedule of HBRA, and these include:

    1. Human biomedical research involving human eggs or human embryos.

    2. Human biomedical research involving —
    (a) the following types of human-animal combination embryos:

    (i) cytoplasmic hybrid embryos;
    (ii) human-animal combination embryos created by the incorporation of human stem cells (including induced pluripotent stem cells);
    (iii) human-animal combination embryos created in-vitro by using —

    (A) human gametes and animal gametes; or
    (B) one human pronucleus and one animal pronucleus;

    (b) the introduction of human stem cells (including induced pluripotent stem cells) into a prenatal animal foetus or animal embryo;
    (c) the introduction of human pluripotent stem cells (including induced pluripotent stem cells) into a living postnatal animal;
    (d) the introduction of human stem cells (including induced pluripotent stem cells) or human neural cells into the brain of a living postnatal animal; or
    (e) any entity created as a result of any process referred to in sub paragraphs (b), (c) and (d).​

    MOH approval must be obtained for all research involving rHBR prior to starting work. PI would have to submit rHBR application together with NTU-IRB approval to MOH via TIARAS. Please inform IRB admin (irb@ntu.edu.sg) for the access to TIARAS system if you are going to conduct any restricted HBRA research.​

    2.4 HBRA contraventions concerning researchers (updated 1 Nov 2017)

    Singapore's Human Biomedical Research Act (HBRA) came into force on 1 Nov 2017. Researchers contravening any part of this legislation may be guilty of an offence and shall be liable on conviction to the following penalties.

    Below is a summarised version to guide researchers. For full details on the relevant sections of this legislation, please refer to Singapore Statutes Online

     

    List of Contraventions and Section Reference

     

    S/N List of Contraventions and Section Reference​ Penalties
    1​

    Duties of researchers conducting HBR – Section 22

    • Proposed research has been reviewed and approved (or exempted) by an IRB;
    • Appropriate consent obtained from research subject.
    • Research does not deviate from approved research proposal unless (i) the deviation has been reviewed and approved by IRB, or (ii) is necessary to mitigate an immediate risk of harm to a research subject.
    • Research is immediately discontinued if IRB has withdrawn its approval for the research
    • If consent of research subject is withdrawn, the further participation of the research subject or further use of the individually-identifiable biological material or health information of the research subject should be discontinued immediately.
    • A researcher must ensure that a minor who lacks sufficient understanding and intelligence, or an adult or minor who lacks mental capacity to give consent, must not be a research subject in any biomedical research unless there are reasonable grounds for believing that biomedical research of comparable effectiveness cannot be carried out without the participation of the class of persons to which the minor or adult belongs.

    Fine: not exceeding $50,000.

    Imprisonment: not exceeding 5 years.

    2

    Compelling person to participate in research - Section 26

    • Coercion or intimidation to compel another person against that person's will to participate or continue to participate as a research subject.

    Fine: not exceeding $100,000

    Imprisonment: not exceeding 10 years.

    3

    Duty to protect health information and human biological material against loss, unauthorised disclosure, etc. - Section 27

    • Every person who has obtained individually‑identifiable information or human biological material must take all reasonable steps and safeguards as may be necessary, including rendering information or material non‑identifiable, to protect such information or material against accidental or unlawful loss, modification or destruction, or unauthorised access, disclosure, copying, use or modification.

    Fine: not exceeding $10,000

    Imprisonment: not exceeding 12 months.

    4

    No re-identification of anonymised information or biological material without consent - Section 28

    • No person who is in possession of or in contact with any information or human biological material can take any action to identify the person from whom such information or material was obtained, except with the consent of the research subject.

    Fine: not exceeding $20,000

    Imprisonment: not exceeding 2 years.

    5

    Restrictions on disclosure of information - Section 29

    • Individually-identifiable information obtained from any research subject should not be disclosed, except with the consent of the research subject.

    Fine: not exceeding $20,000

    Imprisonment: not exceeding 2 years.

    6

    Prohibited human biomedical research - Section 30

    • No person can conduct any prohibited human biomedical research specified in the Third Schedule of HBRA.

    Fine: not exceeding $100,000

    Imprisonment: not exceeding 10 years.

     

    7

    Restricted human biomedical research - Section 31

    • No person can conduct any restricted human biomedical research specified in the Fourth Schedule except:
      • Prior IBR approval obtained; and
      • Prior MOH approval obtained.

    Fine: not exceeding $100,000

    Imprisonment: not exceeding 10 years.


    ​​

     

    3) Conduct of Research Guidelines

    3.1 Requirements of Witness for appropriate consent taking (updated 1 Nov 2017)

    Effective 1 Nov 2017, any appropriate consent taking for studies under HBRA must be taken in the presence of a Witness –
    (a) who is 21 years of age or older;
    (b) who has mental capacity; and
    (c) who must not be the same individual taking the appropriate consent.
    Note: The Witness may be a member of the team carrying out the research of which the individual giving the consent is a research subject.

     The Witness must take reasonable steps to ascertain –
    (a) the identity of the individual giving the appropriate consent; and
    (b) that the consent was given voluntarily without any coercion or intimidation.

     Exemption from requirement for Witness where the research is –
    (a) not invasive;
    (b) not interventional; and
    (c) not restricted human biomedical research (rHBR).
    Note 1: Research that comprises solely of a survey or collection of information from research subjects is treated as not invasive and not interventional.
    Note 2: ​Requirement for witness does not apply to any consent taken before 1 Nov 2017. 

    New informed consent form templates that are compliant with HBRA requirements are available for download on NORA.


    3.2 Requirement for consent of research involving Minors (updated 8 May 2018)

    If your research involves taking consent from a Minor (a person who is below 21 years of age and who has never been married), appropriate consent must be obtained from both the Minor AND at least one adult parent or guardian of the Minor.

    In avoidance of any doubt, parental/guardian consent should be obtained for all research projects involving Minors (21yo below; not married). Where possible, this parental/guardian consent should be taken in the same hardcopy Informed Consent Form (ICF) together with the participant’s consent. If not, a separate hardcopy parental consent form may be obtained. 

    • To facilitate projects in the Social, Behavioural and Educational Research (SBER) domain that are of less than minimal risk (for e.g. online surveys without any sensitive topics or any physical contact) where there is no likelihood of harm, NTU IRB will accept taking parental/guardian consent via "online consent".
        1.  ​"Online consent" could be in the form of emails or web forms seeking parent's/guardian's consent to their child's/ward's participation in a less than minimal risk study.
        2. Names, emails and relationship of parent/guardian should be provided by the Minor (participant) in the usual ICF, and invitations for parental/guardian consent should state that their contact details had been obtained from their child/ward. 
        3. The project Information Sheet and study details (via a website or email) should be provided to the parents/guardians for their review.
        4. Details required from parents/guardians in the online parental consent should include: (1) Name, (2) NRIC number, (3) Email and Telephone number for verification purposes, (4) Relationship to participant, (5) Name of participant.


    • Projects in the Biomedical and Endurance & Human Performance domains are required to obtain parental/guardian consent via the usual hardcopy ICF, and in compliance with HBRA requirements.


    Under HBRA, NTU-IRB can waive this requirement to obtain the appropriate consent of at least one adult parent or guardian for the participation of a Minor if the board is satisfied that -
    (a) the research involves no more than minimal risk to the research subjects; and
    (b) the waiver of parental consent will not adversely affect the rights and welfare of the research subjects; and
    (c) the research may not practicably be carried out unless there is such a waiver, and 

    the research proposal —

    (i) is designed for conditions or for a research subject population for which parental (or guardian) consent is not a reasonable requirement to protect the research subjects (such as neglected or abused minors), and an appropriate mechanism for protecting the minors is substituted; or
    (ii) is of such a private and sensitive nature that it is not reasonable to require permission, (such as adolescents in studies concerning treatment of sexually transmitted diseases); or
    ​(iii) is within the description of such circumstances as may be prescribed.


    ​​​3.3 Information to be provided before taking appropriate consent (updated 1 Nov 2017)

    ​​For HBR, the following information should be provided to the research subject prior to taking appropriate consent:
    (a) the investigational nature of the biomedical research;
    (b) the purpose of the biomedical research;
    (c) the reasonably foreseeable risks, discomforts or inconveniences arising from this biomedical research;
    (d) the benefits which the research subject may reasonably expect from the biomedical research;
    (e) where applicable, whether there are any alternative procedures or treatments available to the research subject, and the potential benefits and risks of such alternatives;
    (f) any compensation and treatment available to the research subject in the event of injury arising from participation in the research;
    (g) any anticipated expenses the research subject is​ likely to incur as a consequence of participating in the biomedical research;
    (h) the extent to which information identifying the research subject will be kept confidential;
    (i) whether individually-identifiable information obtained from the research subject will be used for future biomedical research;
    (j) where applicable, whether biological material taken from the research subject will be destroyed, discarded or stored for future biomedical research;
    (k) whether the participation of the research subject involves information in individually‑identifiable form;
    (l) the circumstances, if any, under which, the research subject will be contacted for further consent, including but not limited to changes in the proposed research, serious adverse events that would lead to a change in the proposed research, the development of capacity by minors to make decisions and any other circumstances which could be specific to a particular research proposal;
    (m) whether the research subject would wish to be re‑identified in the case of an incidental finding if the proposed biomedical research expressly provides for such re‑identification;
    (n) the research subject's right to withdraw his or her consent and the limitations of such withdrawal as specified in that section;
    (o) the person or persons to contact to obtain further information on the biomedical research and to provide feedback in relation to the biomedical research, respectively;
    (p) such ​​​other information as the institutional review board may require;
    (q) such other information as may be prescribed.​​

     

    ​3.4 Advertisements/ Notices for recruitment of research participants (updated 29 Jan 2018)

    Recruiting is part of the informed consent process; therefore the recruitment and advertising methods must be reviewed by NTU-IRB prior to their us​​​​e by an investigator. This review is done to ensure that the information is not misleading to potential research participants, the recruitment is not coercive, and that it accurately describes the likely risks and benefits of study participation. NTU-IRB is particularly cognizant of the special problems of research involving vulnerable populations (e.g. children, prisoners, pregnant women, mentally disabled persons, or economically or educationally disadvantaged persons.)

    NTU-I​RB must review and approve the final copy of advertisements/ notices (including any revisions and modifications to the material) prior to its use, so as to ensure they satisfy the above principles to protect the rights and welfare of the research participants. 

    *This includes advertisements/ notices used for online recruitment

    Advertisements/ Notices sent to NTU-IR​B for review must meet the following requirements:

    (a) ​advertisements must clearly state that volunteers are being recruited to participate in an NTU research project with proper research title and NTU logo.
    (b)​ name and contact details of Principal Investigator (usually a faculty member), and NTU-IRB contact details (Tel: 6592 2495; Email: IRB@ntu.edu.sg) should be provided.
    (c)​ the NTU-IRB project reference number should be stated.
    (d) advertisements should include eligibility criteria.
    (e) advertisements recruiting Minors must explicitly state that parental consent is required for participation (unless NTU-IRB has granted approval for a waiver of parental consent).

    Advertisements/ Notices should NOT contain​ the following:

    (a) ​state or imply a certainty of favourable outcome or other benefits beyond what is outlined in the informed consent form and the application/protocol.
    (b) ​make claims, either explicitly or implicitly, that a procedure or intervention is safe or effective or superior to other standard procedures or interventions.
    ​​(c) use catchy words lik​​e “free” or “exciting.”
    ​​(d) a​dvertisements may state that p​articipants will be paid, but should not emphasize the payment or the amount to be paid (e.g. by suc​h means of larger or bold type).

    ​​​​​3.5 Guidelines for A​dvertisements/Recruitment​ Materials from External Institutions (updated 18 June 2018)

    The following guidelines are intended to offer guidanc​e to researchers from external Institutions on advertising and recruitment of research subjects in NTU community for their studies.

    Once the study has been approved by the respective IRB, the Principal Investigator from the external Institutions should submit the following to NTU-IRB (irb@ntu.edu.sg​) for review:

    (i) IRB approval letter from the respective Institutional Review Board

    (ii) Advertising/recruitment material(s). This needs to be in line with NTU-IRB’s advertising requirements (IR​​B Guidelines - 3.4 Advertisements/Notices for recruitment of research participants​)​

    (iii)  ​Contact details of the external Institutional Review Board that approved the study protocol for our verification

    The ​NTU-IRB Secretariat will review a final version of the advertisement/recruitment materials in order to evaluate the impact of design details such as photographs, images, font sizes, styles and other visual effects before approval can be granted. The NTU-IRB Secretariat will ONLY review the information contained in the advertisement and the mode of its communication as the respective Institutional IRB is expe​cted to rev​iew all the research-related documents and activities and ensure that the rights and welfare of research subjects are protected. The NTU-IRB Secretariat will contact the respective Institutional Review Board and verify the authenticity of the project.  


    3.6 Incident Reporting (updated 20 Apr 2018)


    Fo
    r projects that fall under HBRA, MOH requires Principal Investigators (PIs) to inform their Research Institute, in this case NTU, of any Serious Adverse Events that occur​ during the course of an approved research study. In view of this legislation, NTU-IRB requires PIs to report any incident arising from (a) Protocol Deviation/Non-Compliance, (b) Unanticipated Problem and/or (c) Serious Adverse Events using the Incident Report Form. The categories of incidents to be reported are defined as follow:

    (a) Protocol Deviation/Non-compliance​

    • ​​Changes or departures from the study design/procedures of a research project that are deemed to be under the PI's control but have not been reviewed and approved by the IRB. Such deviations/non-compliance, whether major or minor, are reportable incidents.

    (b) Unanticipated Problem

    • A harm that is "not anticipated" when its specificity and/or severity is inconsistent with the risk information (in terms of nature, severity, frequency, and characteristics of the study population) previously reviewed and approved by the IRB.
    • Examples of unanticipated problems include breach of confidentiality, complications arising from the use of medical devices and Unanticipated Problems involving Risks to participants or others (UPR).
    • ​Even if actual harm does not occur, incidents meeting the above definition must be reported to NTU-IRB through the Incident Report Form.

    (c) Serious Adverse Events

    • Any adverse event associated with the research subject's participation in research that results in any of the following:

    i.     death
    ii.    is life-threatening (places the research subject at immediate risk of death from the event as it occurred)
    iii.   requires inpatient hospitalization or prolongation of existing hospitalization
    iv.   results in a persistent or significant disability/incapacity
    v.    results in a congenital anomaly/birth defect or
    vi.   any other adverse event that, based upon appropriate medical judgment, may jeopardize the research subject's health and may require medical or surgical intervention to prevent one of the other outcomes listed in this definition. Examples of such events include allergic bronchospasm requiring intensive treatment in the emergency room or at home, blood dyscrasias or convulsions that do not result in inpatient hospitalization, or the development of drug dependency or drug abuse.

    • In accordance with section 23(3)(b) of the HBRA, PI must inform NTU immediately of any Unexpected Serious Adverse Event.​​
      • For events that involve death or is life threatening, NTU is required to submit all relevant documentation to Director, MOH within 7 days after knowledge of the event. Additional relevant information has to be submitted to MOH within 8 days of recording of such information.
      • ​For events that do not involve death or is not life-threatening, NTU is required to submit relevant information to MOH within 15 days after knowledge of the event.
         

    PI must submit the completed incident form to irb@ntu.edu.sg. NTU-IRB Secretariat will notify the PI of the outcome of the review. 

    For more information, please send your queries to irb@ntu.edu.sg. ​




    3.7 Incidental Findings (IFs (updated 18 June 2018)

    During the course of research involving humans, findings relating to a subject's health may be discovered that is unrelated to the purpose or objectives of the study. These findings are termed "Incidental Findings" (IFs), which may be of clinical significance that could have potential serious implications for the subject's well-being. In general, a research subject should be allowed to consent if he/she wishes to be re-identified in the case of an IF, if the proposed biomedical research expressly provides for such re-identification. Ethical management of IFs is thus necessary and researchers have and obligation to anticipate these findings and make a plan in advance of starting the research, that addresses what, when and how findings will be communicated to the research subjects.

    In line with NTU's policy on IFs, PIs are to determine from the outset on the potential for IFs occurring, and if these will be released to the subjects. The threshold for reporting IFs, which are the potential medical beneficence of the findings versus the need for respect for persons, should be determined. Based on this, a management plan should be developed by the PI, and these are to be submitted to NTU IRB for review and approval.

    [A detailed guideline on this can be found here]  

      


    3.8 Continuing Reviews (CR) / Study Completion Review (updated 18 June 2018)

    Continuing review (CR) is a post-approval review process to evaluate if a research study is being conducted in compliance with the approved protocol. This is necessary to ensure the continued validity of ethics approval and to assure the protection and welfare of research subjects.

    In line with Singapore's HBRA requirements and ethics guidelines, NTU-IRB requires all projects approved under the non-Exempt category (i.e. Expedited/Full Board review) to fulfil the following:

    (i) PIs should submit ​the Continuing Review Form​​ annually or at intervals appropriate to the degree of risk, until the completion of the study.

    (ii) CR is required until the research study is permanently closed to the enrolment of new research subjects, and all research subjects have completed all research-related interventions/study activities and collection, and analysis of individually identifiable data has been completed.

    (iii) Upon completion of studies, PIs should submit the Continuing Review Form​ (by checking the study completion option) at the earliest possible time, but not more than 3 months after study completion.

    (iv) PIs may use the Continuing Review Form​ to report project withdrawals and suspension/termination. This should be reported within 30 calendar days of withdrawal, and 7 calendar days of suspension/termination of the study, respectively.

    (v) Following reviews by IRB, PIs will be notified for CR outcome.

    Note: The NTU-IRB will withdraw the approval or suspend/terminate the study if there is wilful non-compliance to the CR process.

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