National Statement on Ethical
Conduct in Research Involving Humans
Part 12 - Clinical Trials
A clinical trial is a study involving humans to find out whether an intervention, including treatments or diagnostic procedures, which it is believed may improve a person's health, actually does so. A clinical trial can involve testing a drug, a surgical or other therapeutic or preventive procedure, or a therapeutic, preventive or diagnostic device or service. Any intervention, including so-called "natural" therapies and other forms of complementary medicine, can be tested in this way. Other related disciplines also conduct research which involves similar ethical considerations to those raised in clinical trials.
In pharmaceutical and medical device trials there are established codes of good clinical research practice which define clearly what is meant by a clinical trial for those purposes. 12. Clinical Trials has principal application in the context of biomedical clinical trials but should also apply to any other intervention claiming therapeutic benefit, wherever provided or conducted.
12.1 The aims of every trial must be precisely stated in a protocol presented to and approved by a Human Research Ethics Committee (HREC) and every trial must be conducted by researchers with suitable experience, qualifications and competence and, where applicable, adequate training in relevant procedures including the use of any device being trialed.
12.2 An HREC must consider all aspects of the design of a clinical trial and be satisfied that:
(a) the trial is directed to answering a specific question or questions;
(b) there is a scientifically valid hypothesis being tested which
offers a realistic possibility that the interventions being studied will be at least as effective as standard treatment;(c) where the research is therapeutic, and is therefore intended
and likely to be of direct benefit to participants, there is an acceptable balance between the risks and benefits of the trial;
(d) the methodology provides:
(i) a rationale for the selection of appropriate participants;
(ii) an appropriate method of recruitment;
(iii) adequate, understandable information for the purpose of obtaining participant consent;
(iv) a clear description of the intervention and observation to be conducted; and
(v) a sample size adequate to demonstrate clinically and statistically significant effects;
(e) it has access to adequate expertise or advice to consider the safety of the drugs, medical devices or other intervention under investigation; and
(f) it is familiar with the requirements of the Therapeutic Goods Administration (TGA) in relation to unregistered drugs and devices, particularly the Clinical Trial Notification (CTN) and Clinical Trial Exemption (CTX) schemes, where relevant.
12.3 An HREC, before granting approval to a clinical trial, must be satisfied that the protocol conforms to:
(a) this Statement;
(b) the World Medical Association Declaration of Helsinki;
(c) where relevant, the CPMP/ICH Note for Guidance on Good Clinical Practice (CPMP/ICH-135/95) and the ISO 14155 Clinical Investigation of Medical Devices and the requirements of the TGA; and
(d) any requirements of relevant Commonwealth or State/Territory laws.
12.4 The use of a placebo alone or the incorporation of a non-treatment control group is ethically unacceptable in a controlled trial where:
(a) other available treatment has already been clearly shown to be effective; and
(b) there is risk of significant harm in the absence of treatment.
If there is genuine uncertainty about the net clinical benefit of treatment, a placebo controlled trial or a trial with a no-treatment arm may be considered.
12.5 A researcher must inform an HREC of any business or other similar association which may exist between a researcher and the supplier of a drug or surgical or other device to be used in the trial.
12.6 An HREC must examine those aspects of the budgets of clinical trials which raise ethical issues, including capitation fees, payments to researchers, institutions or organisations involved in the research, current and consequential institutional or organisational costs and costs which may be incurred by participants. It should be satisfied that:
(a) payment in money or kind would not cause researchers to apply pressure to individuals so as to obtain their consent to participate;
(b) payment in money or kind could not influence the findings of the research;
(c) there will be disclosure to the research participants of relevant aspects of those budgets; and
(d) funding is sufficient to conduct and complete the trial so that participants are not disadvantaged by premature cessation.
12.7 An HREC must be satisfied, before approving a clinical trial, that arrangements exist to ensure adequate compensation to participants for any injury suffered as a result of participation in the trial.
12.8 An institution or organisation and its HREC must require the researcher:
(a) to conduct the trial in compliance with the approved protocol;
(b) to provide reports of the progress of the trial to the HREC at
a frequency directed by the HREC that is related to the degree of risk to participants, but at least annually;(c) to inform the HREC of, and seek its approval of, amendments to the protocol including any:
(i) proposed or undertaken in order to eliminate immediate hazards to participants;
(ii) that may increase the risks to participants; or
(iii) that significantly affect the conduct of the trial;
(d) to inform the HREC and the TGA of all serious or unexpected adverse events that occur during the trial and may affect the conduct of the trial or the safety of the participants or their willingness to continue participation in the trial;
(e) to inform the HREC as soon as possible of any new information from other published or unpublished studies which may have an impact on the continued ethical acceptability of the trial or which may indicate the need for amendments to the trial protocol;
(f) to inform the HREC, giving reasons, if the trial is discontinued before the expected date of completion; and
(g) in relation to trials with implantable medical devices, to confirm the existence of or establish a system for tracking the participant, with consent, for the lifetime of the device, and to report any device incidents to the TGA.
12.9 The institution or organisation and its HREC must determine the type and frequency of review appropriate to the drug or device being investigated and to the degree of risk to participants provided that the review occurs at least once a year.
12.10 It may be unethical for a researcher to continue a trial if:
(a) there are or have been substantial deviations from the trial protocol;
(b) side effects of unexpected type, severity, or frequency are encountered; or
(c) as the trial progresses, one of several treatments or procedures being compared proves to be so much better, or worse, than other(s) that continuation of the trial would disadvantage some of the participants.
12.11 In a clinical trial, data must be accurately recorded in a durable and appropriately referenced form and:
(a) data management should comply with relevant privacy requirements, including the Standards Australia Personal Privacy Protection in Health Care Information Systems (AS4400-1995);
(b) if data are of a confidential nature, confidentiality must be observed;
(c) data and records must be preserved for such periods and in such manner as prescribed by laws of the Commonwealth,
the relevant State or Territory or national policies or guidelines; and(d) where materials of biological origin are being used in a trial, records should be preserved for such periods as will enable participants to be traced in the event that evidence of late or long-term effects emerge.
12.12 In trials of therapeutic goods, including pharmaceuticals and biological substances the HREC must follow the requirements of the TGA and the CPMP/ICH Note for Guidance on Good Clinical Practice (CPMP/ICH-135/95).
12.13 In medical device trials, the HREC and the researcher must follow the requirements of the TGA (Australian Device Requirement Version 4, DR4, May 1998) and the ISO 14155 Clinical Investigation of Medical Devices on Human Subjects.
[Preamble] [Part 1] [Part 2] [Part 3] [Part 4] [Part 5] [Part 6]
[Part 7] [Part 8] [Part 9] [Part 10] [Part 11] [Part 12] [Part 13]
[Part 14] [Part 15] [Part 16] [Part 17] [Part 18] [Part 19]
[Appendix 1] [Appendix 2] [Appendix 3]