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Guide
for Investigators
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Activities
Requiring Ethics Review
Necessary
Approvals for Clinical Trial
Investigator's Responsibility
Investigator
Code of Practice
Preparation
for an Ethics Review
REC Review Considerations
Types of Review
Review Decisions
Adverse
Event Reporting
Useful
Links & Resources for Investigators
Activities Requiring Ethics Review
| 1. | Research on human subjects including | |
| • | Body tissue, fluid (even 'waste' or 'extra' tissue, fluid) | |
| • | Records, data (applies to prior collected data in a format linking to individual identifiers) | |
| • | Human genome, stem cell, pre-implantation & human embryo research | |
| • | Collection & storage of 'extra' material for future study | |
| 2. | QA activity involving additional risk, burdens, intrusion of privacy & possibly overlap with research | |
| * | Ethics approval is usually not required in a straight forward clinical audit or analysis of existing / secondary data without identifiers traceable to the subjects | |
Necessary Approvals for Clinical Trial
| 1. | Initial and continual ethical approval | |
| • | Ignoring REC requirement may invalidate approval | |
| 2. | Administrative endorsement from | |
| • | Heads of all departments involving in trial | |
| • | Hospital administration to sign contract (Clinical Trial Agreement) with external sponsor | |
| • | Authorities of non-affiliated study sites | |
| • | Education institute if study is part of a student's course work | |
| 3. | Regulatory requirement, e.g. clinical trial certificate | |
| 1. | Plan and execute study to minimize risks to research subjects to the extent possible. | |
| 2. | Apply to the respective REC for review and approval before commencing a clinical research. All investigators should disclose possible conflict of interest. | |
| 3. | Abide by the REC decisions including terms of approval and study oversight requirements. | |
| 4. | Provide fair and accurate information to prospective subjects regarding nature of research and possible alternatives if subject chooses not to participate. Obtain informed consent from each prospective subject or the subject's legally authorized representative unless waived by the REC, and provide each of them a copy of the consent document the content was which has been approved by the REC. If an investigator has economic interest in the research outcome, it should be disclosed as part of the consent process. Recruited subjects should be updated throughout the research of new information that may be relevant to their willingness to continue participation in the research. | |
| 5. | Monitor subjects' safety and well-being throughout study. Any significant adverse events must be reported promptly to the sponsor, REC and HA Legal Services (through hospital administration). | |
| 6. | Ensure safe keeping of study articles. | |
| 7. | Retain essential research documents and records in a secure and safe manner for up to at least 3 years after completion of study or after the last approval of a marketing application for drug trials, or as demanded by applicable local regulations, or by an agreement with the sponsor, whichever is longer. | |
| 8. | Protect the privacy of subjects and confidentiality of data. Keep disclosures to the minimum necessary and anonymize the data whenever possible | |
| 9. | Do not deviate from, or make changes to the study without prior approval from the REC and trial sponsor, except when it is necessary to eliminate immediate hazards to research subjects or when the change involves purely logistical or administrative issues, and to notify them promptly of such changes. | |
| 10. | Report progress of approved research to the REC, in accordance to the schedule and in the manner prescribed by the REC, but not less than once per year. This includes a final report upon study closure. | |
| 11. | The Principal Investigator (PI) in particular has overall responsibility in technical, administrative and fiscal management of study. | |
Preparation for an Ethics Review
| 1. |
The Application Dossier is designed to facilitate ethics review. |
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| 2. | Investigator must prepare the Application Dossier and submit the required number of copies to the respective Cluster REC office. | |
| 3. | Download MS-word file of the updated Application Form from hospital web-page | |
| 4. | All sections of the Application Form should be duly completed | |
| • | Nil entry is required | |
| • | "As per protocol" is not accepted | |
| • | Information is genuine, accurate and layman friendly | |
| • | The declaration section must be signed by all investigators and endorsed by the COS / Head of Department | |
| • | Endorsement from other involved departments | |
| 5. | Indemnity agreement and clinical trial agreement, where applicable, must be signed by appropriate authorities | |
| 6. | Investigators may be asked to provide further information, to clarify the information and to modify the research protocol as seem fit by the REC. | |
| 1. |
Proposed study has a reasonable expectation in improving health, healthcare or furthering knowledge. |
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| 2. | Methodology is scientifically valid and practically feasible. | |
| 3. | Risks to subjects are minimized to the extent possible (by using procedures that are consistent with sound research design and which do not unnecessarily expose subjects to risk). | |
| 4. | Risks to subjects are reasonable in relation to anticipated benefits. | |
| 5. | Subject selection is equitable and scientifically based. | |
| 6. | Adequate informed consent will be sought from each prospective subject or the subject's legally authorized representative (unless qualified for waiver). | |
| 7. | Payment to subject, if any, should not pose an excessive risk of inducement to the economically disadvantaged. | |
| 8. | There are adequate provisions for monitoring the data collected to ensure safety of subjects. | |
| 9. | There are adequate provisions for protecting privacy of subjects. | |
| 10. | Foreseeable problems after study completion, such as removal of an effective treatment, are adequately addressed. | |
| 11. | Sponsor provides adequate indemnity. | |
| 12. | When vulnerable subjects will be involved, there are necessary additional safeguards to protect their rights and welfare. | |
Full panel or expedited review
The REC has the authority to approve, require modification (to secure approval), or disapprove research applications. Decision categories include:
| 1. |
Approval: The REC will notify applicant in writing stating the (i) research and protocol approved including consent form and other relevant documents, (ii) terms of approval, (iii) approving authority, and (iv) date of approval. |
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| 2. | Conditional Approval: This is suitable if only minor correctable issues are involved. REC will notify applicant in writing detailing the issues / requirements that the investigator has to address. Research should not commence until all such requirements have been addressed and approved. | |
| 3. | Disapproval: The REC will notify applicant in writing stating the reason for its decision. If this happens, the investigator must not conduct the research. The investigator may resubmit an application to the REC if the reasons given for disapproval can be corrected and addressed, or an appeal be made to the HA REC. | |
| 4. | Suspension or Termination of REC Approval: The REC may suspend or terminate a prior approval if the research is not being conducted in accordance with the requirements set forth by the committee or evidence suggest unexpected serious harm to subjects. | |
Investigators are obliged to monitor participants' safety and well-being throughout study. The PI must coordinate and report any adverse events that may reasonably be regarded as caused by, or probably caused by, the study article to the sponsor (if available), respective REC, regulatory agency (if required by law) and the Legal Services Section of HAHO (when there is potential claim and legal implication). This should be done in a timely fashion, i.e. the more serious an adverse event is, the sooner it should be reported. Note that ICH-GCP specifies immediate reporting of SAE to sponsor (para 4.11.1) and prompt reporting of all adverse reactions that are both serious and unexpected to the REC (para 3.3.8c).
Depending on the seriousness and study relatedness of the adverse events, investigators should decide on the necessity to modify the study protocol, the consent form, and to update participants of the previously unknown / unexpected risk.
An adverse event is serious if it causes
i) death or a life-threatening event
ii) hospitalization or prolongation of hospitalization
iii) persistent or significant disability
or incapacity
iv) congenital anomaly or birth defect, or
v) other harms judged by PI to be serious.
The SAE Report Form requires the PIs to estimate,
at the time of reporting, of the causal relationship between study participation
and the adverse event. The study relatedness of an adverse event increases if
it
i) has a reasonable temporal relationship
to intervention
ii) could not readily have been produced
by the subject's clinical state
iii) could not readily have been due to environmental
or other interventions
iv) follows a known pattern of response to
intervention
and particularly if it
v) disappears or decreases with reduction
in dose or cessation of intervention
vi) recurs with re-exposure
Useful Links & Resources
for Investigators
| Clinical Trial Simulator | |
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| Research Methods Knowledge Base | |
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| Statistics & Research, PS&MD, Hospital Authority | |
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| St. George's Hospital Medical School | |
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| Graphpad.com | |
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| Hospital Authority | |
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| Trent Research & Development Support Unit | |
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| StatSoft | |
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| National Institutes of Health | |
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| National Cancer Institute, U.S. National Institutes of Health | |
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| Lawrence Livermore National Laboratory, Institutional Review Board | |
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| Australian Government National Health and Medical Research Council | |
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| The World Health Organization | |
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| U.S. National Institute for Health | |
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| The Journal of the American Medical Association | |
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| National Academy of Sciences, National Academy of Engineering, Institute of Medicine | |
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| RTI International Office of Research Protection | |
Online Tutorial "Basic Training for Personnel Involved in Human Research" |
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| Advisory Committee on Human Radiation Experiments | |
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| National Institutes of Health | |
NIH Research Training Opportunities: Training in the Responsible Conduct of Research |
Webpage developed and maintained by
Clinical Effectiveness Section,
Clinical Standards & Technology Assessment Department
Quality & Safety Division,
Hospital Authority Head Office
Last update: 3 August 2007