Global demand for clinical trial capacity has expanded significantly over the past two decades, with the number of Phase III trials more than doubling since 2000. Australia has emerged as a major destination for clinical research, supported by a strong health and medical research sector and well-established trial infrastructure.
Manufacturers and sponsors looking to conduct trials in Australia need to navigate a layered regulatory framework involving ethics committees, institutional governance processes and oversight by the Therapeutic Goods Administration (TGA).
Although the Australian Government is developing a National One Stop Shop to streamline research approvals, that platform remains in development phase. In the meantime, clinical trials continue to proceed through a multi-stage approval process involving several regulatory and institutional actors.
In this three-part series, we examine the key elements of Australia’s clinical trial regulatory environment.
This Part 1 outlines the principal approval pathways and the roles of key stakeholders.
Clinical trials in Australia
Conducting a clinical trial in Australia requires navigating several distinct regulatory processes, each overseen by different institutions. At a high level, sponsors must:
These processes operate in parallel to ensure that trials are scientifically sound, ethically conducted and appropriately regulated.
Below we step through each of these steps.
Ethics approval
Before a clinical trial can commence in Australia, the protocol must be reviewed and approved by a HREC registered with the National Health and Medical Research Council. The HREC will determine whether the proposed research is ethically acceptable under the National Statement on Ethical Conduct in Human Research. In doing so, the proposal will be considered through the lens of the National Statement’s core values of research merit and integrity, justice, beneficence and respect.
More specifically, the HREC will consider whether the trial is justified by its potential benefit, whether the methodology is appropriate to its aims, whether it is grounded in existing evidence, and whether it will be conducted by researchers with the requisite qualifications, experience and resources. A trial that lacks scientific merit, or is not capable of being conducted with integrity, will not be ethically justifiable simply because participants have consented. HRECs review the protocol and associated trial documents to determine whether the trial is ethically defensible before participants are enrolled.
For eligible multi-centre trials in public health organisations, ethics review may occur under the National Mutual Acceptance scheme.
Site approval
HREC approval does not, of itself, permit a clinical trial to commence at a particular site. Separate institutional authorisation is required from the institution at which the trial is to be conducted, referred to by the TGA as the approving authority.
In granting that authorisation, the institution itself, rather than a regulator, is responsible for considering whether the trial can be conducted appropriately at the site, having regard to matters such as staffing, facilities, resources and local governance requirements. Institutional authorisation will generally only be given following HREC review and the institution being satisfied that the necessary contractual, indemnity, insurance and budgetary arrangements are in place.
This process is distinct from HREC review. While the HREC assesses whether the proposed trial is ethically acceptable, institutional authorisation focuses on whether the site is ready and able to conduct the trial in accordance with the protocol.
TGA oversight of clinical trials involving unapproved therapeutic goods
The TGA’s role in the clinical trial context is not to approve every clinical trial. Rather, its role is to regulate the lawful supply and use of unapproved therapeutic goods in human research.
A therapeutic good will be “unapproved” for this purpose if it is not included in the Australian Register of Therapeutic Goods (ARTG), but also if it is included on the ARTG and is proposed to be used in a way not covered by its existing entry — for example, for a new indication, dosage form, strength, route of administration or other materially different use.
Where a clinical trial involves the supply of such an unapproved therapeutic good, the sponsor must proceed through either the Clinical Trial Notification (CTN) scheme or the Clinical Trial Approval (CTA) scheme before the product can lawfully be supplied for use in the trial (that is, for experimental use in humans in Australia). As set out below, the more novel, technically complex or uncertain the product or protocol, the more likely it is that prior TGA review under the CTA scheme will be required.
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What are the schemes? |
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Under the CTN scheme, the sponsor notifies the TGA of the proposed trial, but the TGA does not evaluate the trial at the time of notification. |
The CTA scheme is for use when prior TGA review and approval of relevant scientific data is required before the trial may commence. |
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Which scheme? |
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The CTN scheme is for use when the HREC has access to appropriate scientific and technical expertise to assess the safety of the product without prior TGA evaluation. |
The CTA scheme is mandatory for certain Class 4 biologicals, subject to limited exceptions, and may also be used where the product is higher risk or the HREC does not have access to the scientific and technical expertise necessary to assess the product’s safety. |
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What is the TGA’s role? |
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Once the CTN has been submitted and the applicable fee paid, and the other required approvals are in place, the unapproved therapeutic good may be supplied for the purposes of the trial. |
For CTA trials, the HREC will review and approve the protocol and monitor the conduct of the trial, however the TGA will also assess the safety of the trial product prior to commencement. The TGA will evaluate data relating to quality, preclinical studies and early clinical safety use, before deciding whether supply should be permitted. |
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For both schemes, the TGA retains an ongoing supervisory role after the commencement of the trial. It may inspect clinical trial sites through its Good Clinical Practice inspection program and also has the power to request information about the conduct of trials. Its focus, however, remains the regulation of the therapeutic good supplied for use in the trial, rather than duplication of the HREC’s ethical review function. |
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Human research that does not involve therapeutic goods are not subject to the CTN or CTA requirements or TGA oversight, although HREC approval is still required.
Wrap up
Conducting a clinical trial in Australia requires more than scientific readiness. Sponsors must also navigate a layered framework of HREC ethics review, individual site governance and approval, and therapeutic goods regulation.
This regulatory architecture is central to Australia’s clinical trial environment and should be understood at the outset of any proposed study.
In Part 2 of this series, we will turn to the key stakeholders in the regulatory framework. In Part 3, we will look at the common ethical and legal issues involved in conducting a clinical trial in Australia.
