Who is ultimately responsible for the conduct of a clinical trial?

The Principal Investigator has the primary responsibility for ensuring the ethical conduct of the research study.  This includes protecting human subjects’ rights, safety and welfare, protocol compliance, and adherence to institutional, state and federal regulations and guidance. The PI is responsible for ensuring informed consent is appropriately obtained from each participant and for appropriately maintaining study records. The PI is also responsible for complying with the financial and administrative policies and regulations associated with the award, overall fiscal management of the project, and conflict of interest disclosure.  

The PI oversees all aspects of a clinical trial from protocol design, recruitment, data collection, analysis and interpretation of results, but some tasks can be delegated to other research team members (Co-Investigators and Key Personnel).  The PI is responsible for ensuring that all research team members have appropriate education, training and qualifications to assume delegated study tests. All study team members are responsible for ensuring that the conduct of the study is compliant with institutional, state, federal and industry guidance and regulations.

Sub-Investigator (Sub-I) / Co-Investigator (Co-I)

The Sub-Investigator/Co-Investigator may perform all or some of the PI functions, but they do not accept primary responsibility for the research study.The sub-investigator/co-Investigator is under the supervision of the PI and is responsible for performing study–related procedures and /or to make important study-related decisions in compliance with the ethical conduct of the study.

Regulatory Coordinator

The Regulatory Coordinator is typically responsible for drafting or editing the protocol document and submitting new protocols, protocol amendments, continuing reviews and safety reports to the appropriate IRB for review. They are responsible for maintaining regulatory binders in accordance with sponsor specifications and general industry standards.  They often are the keepers of the delegation of authority log for key personnel involved in the study.

Data Coordinator

The Data Coordinator is responsible for the overall data management of a research study.  Data points for analysis must be extracted from multiple source documents and entered into specific databases.  Data coordinators ensure accurate and timely data entry in electronic databases, electronic case report forms (eCRFs) or paper case report forms (CRF). They work closely with sponsor monitors and resolve any data queries that may be generated. They also work closely with the research team in the study development process to identify key data points for collection and analysis for investigator initiated trials.

Research Coordinator/ Research Nurse

The Research Coordinator/Nurse oversees and coordinates the daily activities of clinical research studies. They work closely with the clinical teams and investigators to ensure that all protocol required procedures and visits occur according to protocol specified guidelines. Research Coordinators/ Research Nurses generally manage participant enrollment and ensure compliance with the protocol and other applicable regulations. This includes but is not limited to; participant recruitment, obtaining informed consent, educating participants on the details of the research study, assessing participant eligibility, facilitating participant care and follow-up per protocol, creating source documentation, assisting in the assessment of toxicities/adverse events and reporting serious adverse events per IRB and sponsor requirements.

The clinical trials toolkit contains useful information and resources for conducting a clinical trial in Australia. 

The Clinical Trials Environment

Overarching Legislation and Guidance

Clinical trials involving the use of unapproved therapeutic goods (i.e. drugs, medical devices and biologicals) are subject to a number of national laws and regulations, including:

The TG Act and regulations establish two schemes for clinical trials involving therapeutic goods that have not received marketing approval for supply in Australia (i.e. they are ‘unapproved’), these are:

Australia’s Therapeutic Goods Administration (TGA) is the body responsible for administering the CTN and CTA schemes. Clinical trials involving the use of approved therapeutic goods outside their marketing authorisation (i.e. ‘off-label’) also need to go through either the CTN or CTA scheme.

Information on these schemes can be found at:

Not all clinical trials need to be conducted under the CTN or CTA schemes. For example clinical trials involving new surgical techniques, or trials involving the use of approved drugs and medical devices within their marketing authorisation, may not require a CTN or CTA application. The decision whether a clinical trial should proceed via the CTN or CTA scheme is initially for the sponsor and, ultimately, for the reviewing Human Research Ethics Committee (HREC).

A clinical trial conducted under the CTN or CTA scheme requires approval by a HREC (also known in the US as an Institutional Review Board) that is constituted and operating in accordance with the National Statement on Ethical Conduct in Human Research (National Statement) and which has notified its existence to the National Health and Medical Research Council (NHMRC). Further information on the National Statement and registered HRECs is set out below.

The conduct of clinical trials is also governed by further national laws and guidelines, which are discussed below.

Guideline for Good Clinical Practice (CPMP/ICH/135/95)

The ICH Guideline for Good Clinical Practice (CPMP/ICH/135/95) is an internationally accepted standard for the designing, conducting, recording and reporting of clinical trials.

The TGA has adopted CPMP/ICH/135/95 in principle but has recognised that some elements are, by necessity, overridden by the National Statement (and, therefore, not adopted) and that others require explanation in terms of 'local regulatory requirements'. To the extent that there is a perceived inconsistency between the National Statement and the Guideline for Good Clinical Practice, the TGA recommends that the National Statement take precedence.

For more information see:

• ICH Guideline for Good Clinical Practice (ICH-GCP) (Annotated by the TGA)

The National Statement on Ethical Conduct in Human Research (2007)

The National Statement on Ethical Conduct in Human Research 2007 (updated 2018) (National Statement) consists of a series of guidelines made in accordance with the National Health and Medical Research Council Act 1992. It is intended for use by:

• any researcher conducting research with human participants
• any member of an ethical review body reviewing that research
• those involved in research governance and
• potential research participants.

The National Statement is developed jointly by NHMRC, the Australian Research Council (ARC) and Universities Australia (UA).

Conformance to the National Statement is a prerequisite for receipt of NHMRC or ARC funding.

The National Statement requires that all clinical trials (whether they fall under the CTN or CTA schemes or not) be approved by a properly constituted HREC.

For more information see:

• National Statement on Ethical Conduct in Human Research 2007 (updated 2018)

For information on HRECs and the TG Act:

• The Australian Clinical Trial Handbook

Australian Code for the Responsible Conduct of Human Research

The Australian Code for the Responsible Conduct of Research, 2018 (the Code) guides institutions and researchers in responsible research practices and promotes research integrity. It assists institutions in developing their own employee codes of conduct and procedures for the investigation of allegations of research misconduct by providing a comprehensive framework of acceptable academic standards.

The Code is supported by a series of guides, including the Guide to Managing and Investigating Potential Breaches of the Code.

Institutions and other entities wishing to be eligible to receive NHMRC or ARC funding must abide by the Code and report research misconduct to NHMRC and ARC.

For more information see:

Privacy Act 1988

Clinical trials involve the collection, use or disclosure of personal and ‘sensitive information’ (sometimes all three) or access to personal or sensitive information held by third parties (such as Medicare, a General Practitioner’s surgery, or a public hospital). ‘Sensitive information’ includes medical information as well as information about an individual’s racial or ethnic origin or sexual orientation or practices, among other characteristics.

Clinical trials that require access to personal or sensitive information held by the Commonwealth are subject to the Privacy Act 1988 (Cth). If the sponsor conducting the clinical trial, or the site at which the trial is being conducted, is a Commonwealth agency, medium-large company, a private university or the Australian National University, all activities related to the collection, use or disclosure of personal and sensitive information may be subject to the Privacy Act 1988 (Cth).

Even if the national Privacy Act 1988 (Cth) does not apply to your clinical trial, most States and Territories have their own privacy laws and law protecting medical records.

If your organisation or clinical trial is subject to the national Privacy Act 1988 (Cth) then the reviewing HREC must consider and abide by a series of guidelines developed by NHMRC relating to the use and disclosure of information in medical research. Your trial must also abide by the Australian Privacy Principles.

For more information see:

Other laws

Some clinical trials may be subject to special rules. For example:

Other guidance

Planning a clinical trial

The information below may be helpful if you are thinking about conducting a clinical trial in Australia.

Finding a suitable site and/or Clinical Trial Network partner

The following resources or organisations may help you identify a site at which to conduct your clinical trial or a clinical trial network that could partner with you. Networks are a useful source of contacts, expertise and potential investigators.

For more information see:

Feasibility and Research Governance

Early and thorough planning is essential to timely and efficient clinical trial commencement. Through the development of its national Good Practice Process for Site Assessment and Authorisation Phases of Clinical Trial Research Governance (Good Practice Process), NHMRC demonstrated that significant improvements in clinical trial start up times can be achieved when sponsors, investigators and clinical trial sites communicate effectively and if a proper feasibility assessment is undertaken prior to the submission of documents for ethics and site assessment and authorisation.

Many Australian States and Territories have adopted standard Clinical Trials Research Agreements. Use of these Agreements is a de facto standard in many jurisdictions and is compulsory in others.

For more information see:

Developing a Protocol

Australia’s leading public funder for health and medical research (NHMRC) supports the use of the SPIRIT Statement and Checklist in the development of protocols.

• SPIRIT Statement and Checklist

How to apply for ethics approval

Human research in Australia must be conducted in an ethical and responsible manner. Ethics approval and oversight is provided by Human Research Ethics Committee (HREC) which are often (but not always) located at the site(s) where the clinical trial will take place.

A clinical trials conducted under the CTN or CTA scheme requires approval by a HREC that is constituted and operating in accordance with the National Statement on Ethical Conduct in Human Research 2007, updated (National Statement) and which has notified its existence to NHMRC.

The National Statement requires that all clinical trials (whether they fall under the CTN or CTA schemes or not) be approved by a properly constituted HREC. Conformance to the National Statement is a prerequisite for receipt of NHMRC funding.

NHMRC has developed a national Human Research Ethics Application (HREA) for use by sponsors and researchers conducting any form of human research, including clinical trials. While the HREA is a national form, its acceptance by HRECs may be influenced by the governing rules and policy of the HREC’s host institution, or by a state and territory government.

Before you start to complete an HREA, make sure you ask the ethics office to which you plan to submit it whether they are able to accept the HREA. They may advise you to use another form.

If you are conducting a clinical trial at multiple centres (i.e. at two or more sites, each of which requires separate approval) you may need to submit your ethics application to multiple HRECs. However, under the National Statement, institutions are encouraged to reduce duplicate ethics review and accept the ethics approval of another institution.

Some States and Territories operate their own National Mutual Acceptance scheme for multi-centre human research taking place in public hospitals (see below).

For further information see:

Finding an Ethics Committee

NHMRC maintains a list of HRECs that have notified NHMRC of their existence. These HRECs have declared that they are constituted and operate in accordance with the National Statement.

NHMRC has also ‘certified’ the ethical review process of a number of institutions under its National Certification Scheme of Institutional Processes related to the Ethical Review of Multi-centre research (National Certification Scheme). The National Certification Scheme is a voluntary scheme intended to provide assurance that the policies, processes and procedures of an institution and its HREC comply with an agreed set of national criteria for the conduct of an ethics review of multi-centre human research.

Under the National Approach to Single Ethical Review, institutions are encouraged to accept the ethics review of a NHMRC-certified HREC. Many (but not all) certified institutions are also recognised under the National Mutual Acceptance (NMA) scheme, a system for single ethics review operating in New South Wales, Queensland, South Australia, the Australian Capital Territory and Victoria.

Before you complete your ethics application you should consider which jurisdictions and institutions will need to approve your application, and ask them whether they will accept a single ethics approval under either the National Approach to Single Ethical Review or the NMA scheme.

For further information see: 

Ethics Resources to help you apply

The following resources may assist you to prepare your ethics application and apply for approval:

Insurance and Indemnity, standard fees & funding

Indemnity and insurance requirements for clinical trials both in the public and private sectors vary across Australia and between institutions. However, a number of initiatives have been undertaken to improve constituency and transparency, including the development of standard indemnity forms.

For more information see:

Fees

There are fees associated with conducting a clinical trial in Australia. Fees may be determined at an institutional level or by a regulator (e.g. CTN and CTA application and notification fees).

For more information see:

Funding

NHMRC funding supports research across the full spectrum of health and medical research, from basic science through to clinical, public health and health services research. For information on funding eligibility and how to apply for funding click on the link below:

The Australian Research Council (ARC) has funding programs that come under the umbrella of the National Competitive Grants Program (NCGP), which supports the highest-quality fundamental and applied research and research training through national competition.

For more information see:

• National Competitive Grants Program

The Australian Government has a number of initiatives and R&D concessions which may apply to your clinical trial. Refer to the links below for more funding information:

Registration of a trial, trial conduct information and closing the trial

Trial registration

Prospective trial registration is important for patient recruitment and now widely accepted as an essential part of an overall strategy for improving research transparency. HRECs may require evidence of trial registration as a condition of granting ethics approval (National Statement). Trial registration is also a condition of NHMRC-funding and a prerequisite for many medical journals.

Refer to the links below for information on registering a clinical trial:

Conducting Responsible Clinical Trials

The Australian Code for the Responsible Conduct of Research (the Code) guides institutions and researchers in responsible research practices and promotes research integrity.

Researchers and sponsors are also expected to follow Good Clinical Practice and to report any serious protocol and GCP breaches in a timely and transparent manner.

For more information:

Training

A range of training material has been developed for researchers, governance officers and other clinical trial proponents. While some materials are free to use, others are fee-for-service.

Competencies have been developed to have better trained staff involved in the conduct and oversight of clinical trials. For more information:

Safety Monitoring and Reporting in Clinical Trials

Under the National Statement, HRECs are responsible for approving any monitoring and reporting arrangements. Standard reporting frameworks for clinical trials are set out in:

Closing the trial

Closing a clinical trial will require notifying a number of parties, including the approving HREC. If the trial was funded by NHMRC a final report may also need to be submitted.

For further information see:

• NHMRC Reporting
• TGA completion advice

Clinical study report

This document is required for in order to be compliant with GCP standards. For more information link to:

Publishing results

You should have a plan for the dissemination of clinical trial results. The Australian Code for the Responsible Conduct of Research states that researchers have a responsibility to their colleagues and the wider community to disseminate a full account of their research as broadly as possible. Dissemination of findings is also an important ethical matter that will be considered by a HREC.

For more information link to:

Note, some international jurisdictions mandate publication of results and clinical data:

Submitting a report to a marketing authorisation body

• TGA: Prescription medicines registration process
• TGA ARTG market approval

Post completion

Other resources

NHMRC eLearning Modules

The NHMRC eLearning 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.

These modules provide an introduction to the clinical trials environment, clinical research ethics and ethics review and research governance processes.

Useful links to organisations and clinical research networks

• Medicines Australia - Medicines Australia is the national peak body that represents the discovery-driven pharmaceutical industry in Australia
• Medical Technology Association of Australia (MTAA) - MTAA is the national association representing companies in the medical technology industry.
• Australian Clinical Trials Alliance (ACTA) - ACTA is the national peak body to support and represent the networks of clinician researchers that conduct investigator-initiated or "public-good" clinical trials within the Australian health system.

Australian Intellectual Property Toolkit for Collaboration

The Australian IP Toolkit for Collaboration (IP Toolkit) contains guides and tools to help researchers use and manage intellectual property (IP) in collaboration. It can be used by anyone wishing to undertake a collaboration project involving business and research.

The IP Toolkit is a joint project between the Department of Industry, Innovation and Science with IP Australia designed to facilitate, simplify and improve collaboration between researchers and industry.

Working Together – A guide to relationships between health consumer organisations & pharmaceutical companies

The Working Together Guide provides a roadmap that can help to achieve the best outcomes for health consumers, carers and families. The roadmap provides the basic principles and suggestions that can be used as a useful resource that can assist with building and maintaining a valuable collaboration. The guide was developed by the Consumers Health Forum of Australia and Medicines Australia.

Australian clinical trials real stories

Real stories from patients, researchers and health care providers.