Clinical trials

Ask yourself:

• What is the exact 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? (This of particular relevance if you intend the trial to be part of a marketing submission; see European Union Guidelines adopted in Australia).
• Is the trial design appropriate?
• Are participant numbers or event numbers sufficient to give adequate statistical power to detect a difference in treatments, should one exist, or demonstrate non-inferiority? Or, to put it another way, can the trial answer the proposed research question or will the data be equivocal? (This aspect of design is often overlooked, but represents a genuine ethical consideration undertaken by HRECs and needs professional statistical consideration).
• Have you considered the ongoing treatment of trial participants, should they respond to the unapproved medical product under investigation? Building in a trial extension provision into the original protocol design not only fulfils good clinical practice requirements, but also can allow such treatment to continue without having to put together another trial proposal after the initial trial ceases. Of course, this is not the only way to provide ongoing treatment post-trial, but is a point to consider in the planning process.

Ask yourself:

• Can your trial obtain an adequate number of participants?
• Should the trial be extended to additional sites to ensure recruitment? (Dealing with this early reduces the likelihood of additional CTN applications being required later. It also works towards adequate recruitment to satisfy statistical requirements).
• Do you have adequate resourcing, facilities and oversight of the protocol?

Clinical trials must be designed so that they comply with the principles set out in the following guidelines:

• National Statement on Ethical Conduct in Human Research 2023 (National Statement) – (National Health and Medical Research Council)
• Australian Code for the Responsible Conduct of Research (developed jointly by the National Health and Medical Research Council, the Australian Research Council and Universities Australia)
• if the therapeutic good has not been included on the Australian Register of Therapeutic Goods (ARTG), then it is subject to the Therapeutic Goods Act 1989 (Cth)
• other state or federal legislation as relevant.

Researchers are also subject to professional codes of conduct – such as the Australian Medical Association or the Australian Psychological Association – when they are conducting research.

• Clinical trials of medicines and medical devices also must comply with ICH Guideline for Good Clinical Practice – Integrated addendum to ICH E6(R1).
• Clinical trials of medical devices must also comply with ISO 14155:2020 Medical devices – Clinical investigation of medical devices for human subjects: Good clinical practice (ISO). This standard will be replaced by ISO/CD 14155 which is currently under development.

Researchers must consult these guidelines when preparing their clinical trial submission.

Researchers must design their clinical trial to ensure that it meets the requirements of GCP in addition to the National Statement and other relevant guidelines.

The GCP guidelines detail the requirements for trial documentation, protocol amendments, requirements such as indemnity, reporting lines for adverse events and provision of medical care for trial participants.

The Therapeutic Goods Administration (TGA) has adopted the European Union version of these guidelines in Australia. The TGA advice includes specific comments from the TGA relevant to the Australian context.

The National Statement requires that, before granting approval to a clinical trial, a Human Research Ethics Committee (HREC) must be satisfied that the protocol conforms to:

• the National Statement
• the World Medical Association Declaration of Helsinki
• where relevant, the CPMP/ICH Note for Guidance on Good Clinical Practice, the ISO 14155 Clinical Investigation of Medical Devices and the requirements of the TGA
• any requirements of relevant Commonwealth or state/territory laws eg 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.

The following clinical trials will need to be referred to the insurer via the Office of Risk and Assurance:

• trials involving pregnant women
• trials involving children five years of age or less
• trials involving blood plasma and whole blood products
• first in human phase 1 trials
• any trial which is to be undertaken outside of Australia. Some countries require local insurances and the insurer may arrange cover if a specific request is made and a fee of approximately $4000 plus fronting fees will be charged.

If you are a sponsor conducting a trial at Macquarie University, provide a table listing the documents that you are submitting for HREC review. This will ensure the correct documents are listed on any approval correspondence. Ensure the table documents the name, version number and date of each document you are submitting for review.

Sometimes sponsors contact the HREC requesting the names and contact details of HRECs members. It is a policy of Macquarie University not to provide this information. The HRECs are constituted in accordance with the National Statement.

Consult our fee schedule for the most up-to-date HREC fees applicable to the review of commercially sponsored clinical trials.

Once a clinical trial has received HREC and institutional approval, the trial must be monitored.

The Macquarie University HRECs have adopted the NHMRC guidelines for:

• safety monitoring and reporting in clinical trials involving therapeutic goods
• reporting of serious breaches of GCP or the protocol for trials involving therapeutic goods.

Macquarie University HREC approval is:

• valid for five years
• contingent on submission of annual progress reports.