Researchers initiating clinical trials in Metro South Health must have evidence of Good Clinical Practice (GCP) Training, clinical trial design, resource issues, ethical clearance, research governance authorisation, Metro South Health policies and procedures as a minimum. Information on ethical clearance, principles of research conduct, regulatory considerations and research governance specific to clinical trials are found in this section of the website.

NHMRC have developed learning modules on the Australian clinical trials environment, ethical issues related to clinical trials and governance relevant to clinical trials.   Whether you are a researcher, in a research office or just wanting to find out more about how clinical trials are conducted, these modules use interactive learning, interviews with experts and knowledge reviews to provide an overview of the nature and importance of the clinical trials environment and approval process in Australia.

A Sponsor will generally approach the Metro South Health institution or department to conduct a clinical trial.

There are numerous considerations that should be made when planning a clinical trial – some of these are as follows:

Clinical trial design

• What is the exact research question this clinical trial is intended to answer?
• What is the primary outcome variable? Is this readily measured?
• Is it a direct measure of outcome or do you intend to rely on surrogate endpoints?
• Are these outcomes those specified by guidance documents as the preferred measures for the outcome of interest?
• Is the clinical trial design appropriate?
• Are subject numbers or event numbers sufficient to give adequate statistical power to detect a difference in treatments should one exist, or demonstrate non-inferiority (i.e. can the clinical trial answer the proposed research question or will the data be equivocal)? (This aspect of design represents a genuine ethical consideration undertaken by the Metro South Health Human Research Ethics Committee (HREC) and needs professional statistical consideration).
• Have you considered the ongoing treatment of clinical trial subjects should they respond to the unapproved medical product under investigation? Building in a clinical trial extension provision into the original research project design not only fulfils Good Clinical Practice (GCP) requirements but also can allow such treatment to continue without having to put together another clinical trial proposal after the initial clinical trial ceases. Of course, this is not the only way to provide ongoing treatment post- clinical trial, but is a point to consider in the planning process.

Participant and staff numbers and resources

• Are your clinical trial centre(s) likely to be able to provide an adequate number of participants for the clinical trial?
• Should the clinical trial be extended to additional sites to ensure recruitment? (Dealing with this early on reduces the likelihood of additional Therapeutic Goods Administration Clinical Trial Exemption Form (CTX) or Clinical Trial Notification Form (CTN) ( https://www.tga.gov.au/form/ctn-scheme-forms ) applications being required later on. It also works towards adequate recruitment to satisfy statistical requirements).
• Do you have adequate resourcing, facilities and oversight of the Research Protocol (RP)?

Site master file

The site master file for a clinical trial should contain all the essential documentation:

• For commercially sponsored research projects, sponsoring companies will normally provide the site master file complete with tab separators for ease and consistency of filing.
• For research projects conducted on behalf of smaller companies or for investigator-initiated research projects.
• Financial documentation such as the clinical trial agreement may be filed in a separate location to the site master file or as per sponsor request.
• When performing sponsored clinical trials of pharmaceutical products, the site pharmacy will usually keep investigational product shipping, receipt and accountability documents. The site itself does not have to replicate these documents. However, the records must be made available to sponsors monitors and auditors.

Documentation of investigational site qualifications and training records

The investigator(s) should:

• Maintain an up-to-date Curriculum Vitae (CV) and review as agreed with the sponsor.
• Be qualified by education, training, and experience to assume responsibility for the proper conduct of the research project.
• Meet all the qualifications specified by the applicable regulatory requirement(s). Current medical practitioner registration details and similar documentation should be referenced in the CV.
• Maintain a list of appropriately qualified and board registered persons to whom the investigator has delegated significant research-related duties. The list is in the form of a Delegation Log and delegated duties should be captured and signed and dated by the investigator on a per person basis. The delegation log may be provided by the Sponsor company but for investigator-initiated research project a separate site log should be developed.

Legal requirements

Some legal requirements to consider are:

• Are adequate indemnity provisions in place for the clinical trial, including for the staff involved? Note that some indemnity cover does not include clinical trial related activities or the use of experimental treatments.
  • See Indemnity and Insurance Arrangements for Clinical Trials in the Public and Private Sectors in Australia. Report to the National Health and Medical Research Council (May 2014)
• Do participant informed consent documents contain a full description of the requirements, risks and benefits of clinical trial participation, in plain English, such that participants can make an informed decision?
• Are the investigational products correctly labelled and packaged according to the Pharmaceutical Inspection Convention Pharmaceutical Inspection Co-Operation Scheme?

From: The Australian Clinical Trial Handbook: A simple, practical guide to the conduct of clinical trials to International standards of Good Clinical Practice (GCP) in the Australian context.

Clinical trial resources

Australia’s clinical trials environment is complex, with various responsibilities resting with institutions, private organisations and companies, State or Territory Governments and the Commonwealth Government.

Below is a selection of resources that may be useful when conducting a clinical trial in Metro South Health.

• Therapeutic Goods Act 1989 (Cth) (TG Act)
• Therapeutic Goods Regulations 1990 (Cth)
• Therapeutic Goods Administration (TGA) Clinical Trial Notification (CTN) / Clinical Trial Exemption (CTX) Schemes
• Guidance for Good Clinical Practice – ICH GCP (Annotated by TGA)
• The National Statement on Ethical Conduct in Human Research
• Guidance for Safety Monitoring and Reporting in Clinical Trials; involving therapeutic goods
• NHMRC Position Statement: Monitoring and Reporting of Safety for Clinical Trials
• Data Safety Monitoring Boards
• Risk-based Management and Monitoring of Clinical Trials involving Therapeutic Goods
• Reporting of Serious Breaches of Good Clinical Practice (GCP) or the Protocol for trials involving therapeutic goods
• Australia Online Forms Website
• Australian Clinical Trials (NHMRC) 
• Clinical Trials Toolkit
• MSH Research Management Policy and Procedures

Please see our Quick links, tools, forms and templates page for additional relevant resources for clinical trials.

Clinical trial registration

Clinical trial registration is the process whereby key details about the design, conduct and administration of planned clinical trials are made available on a publicly accessible database known as a clinical trial registry. In Australia, registration must occur prospectively, that is before enrolment of the first participant. Prospective clinical trial registration is now widely accepted as an essential part of an overall strategy for improving research transparency.

The Declaration of Helsinki, which is the cornerstone document guiding the ethical conduct of research in humans by physicians, now explicitly states that “every clinical trial must be registered in a publicly accessible database before recruitment of the first subject.” This approach is supported by the International Committee of Medical Journals Editors (ICMJE) which includes many of the world’s leading journals. In 2004, ICMJE declared that they would not consider a clinical trial for publication without evidence that it had been registered in a publicly accessible clinical trials registry prior to enrolment of the first participant.

The World Health Organization (WHO) considers the registration of all interventional clinical trials to be “a scientific, ethical and moral responsibility”.

In Australia, the Australian and New Zealand Clinical Trials Registry (ANZCTR) is one of the Primary Registries in the WHO Registry Network (link is external). To register a clinical trial, submit the details directly to Australian and New Zealand Clinical Trials Registry or an alternative ICMJE approved registry.

Clinical trials registration is also important for participant recruitment. Registration allows people interested in participating in a clinical trial to search for relevant clinical trials on a single website. Registration also assists health professionals to identify relevant clinical trials for their patients.

Researchers should register clinical  trials as early as possible and ensure information such as contact details and clinical trial status is kept up to date. To assist people interested in participating in a clinical trial, language used in the general title and the lay summary should be brief, clear, written in plain English and easy to for a lay person to understand.

Ethical clearance - clinical trials requirements

Clinical trials, due to the exposure of humans to as yet unproven treatments, pose additional risks and consequently have tighter controls and reporting requirements than some other research projects.

For medicine and device research: Whether you are a researcher involved in a collaborative clinical trial project, a researcher involved in a commercially sponsored clinical trial, or a contract research organisation, you will need to develop an agreement between the parties involved in the research.  Clinical trial advancement requires assured processes and understanding between the Coordinating Principal Investigator (CPI) (lead) and participating sites. The primary focus is to achieve timely and efficient research governance authorisation for multi-centre clinical trials so that clinical trials can commence as soon as possible following HREC ethical clearance.

A parallel process of research governance authorisation is strongly recommended to ensure timely commencement of a clinical trial at Metro South health that has both ethical clearance and research governance authorisation.

You may also need to arrange for indemnity for your research institution, research premises or ethics committee. Standard templates for clinical trial agreements and indemnities have been developed and should be used wherever possible in order to minimise the need for legal review. For clinical trials and post marketing research, the templates for contracts and indemnities are maintained by Medicines Australia.

Clinical trial specific ethical clearance requirements, in addition to standard submission requirements include:

• brochures for patients
• HREC only indemnities 
• certificate of insurance
• investigators brochure
• Radiation Safety Report – if clinical trial is using ionizing radiation.

Research governance - clinical trials requirements

A parallel process of research governance authorisation is strongly recommended to ensure timely commencement of a clinical trial at Metro South health that has both ethical clearance and research governance authorisation.

You may also need to arrange for indemnity for your research institution, research premises or ethics committee. Standard templates for clinical trial agreements and indemnities have been developed and should be used wherever possible in order to minimise the need for legal review. For clinical trials and post marketing research, the templates for contracts and indemnities are maintained by Medicines Australia.

Commercially sponsored clinical trials

Following feasibility and site selection for a clinical trial there are specific tasks required of the sponsor/contract research organisation, and negotiation of additional assistance may be agreed for the clinical trial. As a sponsor/ contract research organisation, communication with clinical trial site personnel is essential to ascertain local site requirements for research governance.

The Site Specific Assessment (SSA) form, along with the supporting documents, is the vehicle for transferring all essential clinical trial documents from the Principal Investigator/ Clinical Trial Coordinator to the Metro South Health Research Governance Office.

Research governance authorisation requirements

In addition to standard submission requirements include:

• Medicines Australia Standard Indemnity
• Certificate of Insurance
• eCTN acknowledgement
• Copies of Good Clinical Practice (GCP) qualifications of research team