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Clinical trials ethics review at Macquarie University

Considerations before you apply.

Macquarie University's Human Research Ethics Committee oversees the ethical review of clinical trials conducted at Macquarie University and Macquarie University Hospital and Clinical Services, or by our staff, students and visitors. Our review ensures that every trial protects the safety, rights and wellbeing of participants and is conducted in line with the National Statement on Ethical Conduct in Human Research and the relevant national standards for clinical trials. You can find out more about the strict safety and ethical standards researchers must meet on the Researchers page at Australian Clinical Trials.

What we review

The World Health Organisation (WHO) defines a clinical trial as any research study that prospectively assigns human participants or groups of humans to one or more health-related interventions to evaluate the effects on health outcomes (WHO, 2020).

We review Phase II, III and IV clinical trials. We do not review Phase I (first-in-human) trials, these are reviewed on our behalf by the Bellberry Human Research Ethics Committee. If you are planning a Phase I trial, please contact Bellberry directly.

Fees

Fees apply to clinical trials with an external sponsor, whether commercial or non-commercial.

What the HREC must be satisfied of

Before granting approval for a clinical trial, the National Statement requires that a HREC be satisfied that the protocol conforms to:

GCP compliance

For more information on Good Clinical Practice compliance, see the Australian Clinical Trial Handbook and the Australian Code for the Responsible Conduct of Research.

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?

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.

When submitting your clinical trial, you must provide the following documentation:

  • research ethics application form (HREA) available via the MQ Forms for Research Applications (FoRA) system
  • research protocol
  • participant information and consent forms (PICFs) and participant study summary on Macquarie University letterhead
  • a data management plan
  • a table listing the documents that you are submitting for HREC review
  • if relevant:
    • a standard indemnity
    • an investigator’s brochure
    • any other documents, such as patient cards, advertisements, specifications etc.
    • a radiation risk assessment, for studies exposing participants to a higher than normal radiation doses
    • a scientific review or an approval letter from another Australian HREC, if a phase 1 clinical trial
    • for clinical trials being conducted at Macquarie University Health premises and involving Macquarie University Health patients or staff, they must have institutional endorsement prior to submitting ethics application. The clinical research governance endorsement letter will need to be included.

All new applications will be reviewed at the full HREC meeting. Any subsequent submissions may be reviewed at either the full HREC meeting or the executive meeting.

Ethics approval is granted for a period of 5-years, contingent upon submission of an annual report within three  months of the anniversary of the project approval date. Please note,  site authorisation and/or governance approval is required before commencing any research activities.

HREC Submission Requirements for Clinical Trials

The table below outlines documents that may be required from the Sponsor at the start and throughout the trial for submission to Macquarie University HREC. While not exhaustive, this list serves as a guideline to streamline the submission process and minimise unnecessary submissions.

Document type

Submission requirements

Protocol

A clean, version-controlled, searchable copy containing index and bookmarks is required for the initial submission. Subsequent submission of amendments requires in addition a tracked version.

Protocol Clarification Letters

A description of the rationale for the document and any impact on participants is required.

Participant Information Sheet and Consent Form (PICF)

A clean and version-controlled copy is required for the initial submission. Subsequent submission of updated PICFs requires in addition a tracked version, and a participant summary of changes.

Where the complexity of a PICF warrants a participant summary, this must be included at the beginning of the main PICF.

This includes consent document such as Pregnancy PICF, treatment beyond progression, optional/ unspecified future research PICF etc.

Investigator’s

Brochure (IB)

A clean, version-controlled, searchable copy containing index and bookmarks is required for the initial submission. Subsequent annual submissions of update IBs require in addition a tracked version

If the IB amendment requires updates to PICF, the updated IB and PICF must be submitted together.

Product Information

If an approved drug for an approved indication is used in the study, a Product Information sheet should be provided.

Curriculum Vitae (CV)

A CV is required only for the PI. CVs for other investigators may be requested, where relevant.

Radiation safety report

Required, if applicable. Post-approval, if the radiation risk changes, the HREC must be informed by way of an amendment, the PICF updated, and participants reconsented.

Advertising

A clean and version-controlled copy is required for the initial submission. Subsequent submission of updated material requires in addition a tracked version.

Study specific recruitment material that will be provided to a participant must be reviewed by the HREC and listed as an approved document.

Other participant documents

Other participant facing documents such as surveys, questionnaires, ID cards, etc. are required. Updates must include a tracked and clean copy.

Other HREC approvals or rejections

If the research has been reviewed and approved by another Australian HREC, the initial application is to be submitted as an EAEF (Externally Approved Ethics Form). Correspondence between the other HREC and the researcher and the final approval letter must also be provided. Note: for legacy phase I studies, subsequent amendments should also be submitted to the MQ HREC.

Letters from sponsor

Letters informing the PI of significant changes to the study (e.g. early termination).

HREA

If there is no prior approval in place, the initial application must be submitted via HREA.

Change of PI

The updated PICF including the new PI and the completed CT-SOP-03.

Annual Progress reports

Due annually within 3 months of the anniversary of the initial study approval.

Notification of site closure

Not required unless due to safety issue or early termination.

Note: Final Report acts as notification of site closure in all other cases.

Final report

Due at the end of the project/discontinuation, after the study is closed out at the site. Pending safety, PD, or amendment issues need to be finalised before the final report is submitted.

Documents not requiring HREC submission

  • Insurance certificates (HREC Review Only indemnity applies where   the trial is conducted at, and patients are seen, at MQ)
  • Word/PDF versions of previously approved   screenshots
  • Translation certificates from US/UK   English to Australian/UK English
  • CTN (Clinical Trial Notification)
  • Social media plan/policy   in relation to advertising (not required to be submitted but must be in place)
  • GP letter/letter to   healthcare provider
  • End of study enrolment
  • Change in central lab   details (name or address details), unless PICF amendment is required as a   result of this change
  • Clinical Study Reports
  • IMPD (Investigational   Medicinal Product Dossier)
  • GMP (Good Manufacturing   Practice) compliance certificates
  • IB validation (where the   IB has been reviewed and no update is required, this should be conveyed to   the HREC)
  • IB updates where there   are no patients on treatment with the particular drug and there are no safety   issues requiring prior participants to be contacted
  • Product information sheet   updates
  • Sponsor progress reports   (where there are no safety issues)
  • Sponsor memos (e.g.   protocol clarifications, administrative letters) not affecting participant   safety

The Macquarie University HRECs have adopted the NHMRC guidelines for safety monitoring and reporting in clinical trials involving therapeutic goods.

HREC Submission Requirements: Safety Information

In line with the NHMRC guideline Safety monitoring and reporting in clinical trials involving therapeutic goods the MQ University HREC does not require the submission of individual SAEs, Six-Monthly Line Listings or individual SUSARs.

Document type

What is communicated

Timelines and further review

SSI: Urgent safety measure (USMs)

Reasons for the urgent safety measure; measures taken and further actions planned.

Reported within 72 hours of receipt from the Sponsor. Submitted via an AE form.

The HREC will acknowledge receipt of, but will not approve, USMs.  Submission of any revised trial documentation or new participant facing documents resulting from the SSI should be submitted via an amendment.

SSI: Notification of an amendment

Details of the significant safety issue; further actions planned.

Reported no later than 15 calendar days of the Sponsor becoming aware of the issue.

Submission of any revised trial documentation or new participant facing documents resulting from the SSI should be submitted via an amendment.

SSI: Temporary halt of a trial/early termination of a trial for safety reasons

Reasons for the halt/early termination; the scope of the halt (e.g., suspension of recruitment or cessation/interruption of trial treatment); measures taken and further actions planned.

Reported no later than 15 calendar days of the Sponsor’s decision to halt the trial/terminate the trial.

Where it is necessary to seek ethical review of related actions (e.g., informing participants or arranging continuing care and follow-up), a letter describing these actions should be submitted to the HREC within 15 calendar days of the temporary halt/early termination should be submitted via an amendment

Annual safety report/DSUR

The Executive Summary of safety information produced for international regulators, such as a DSUR, may serve as the annual safety report.

Separate submission of DSUR is not required unless there are updates to the safety risk profile of the study drug which requires action and patient notification.

All other DSUR reports should be submitted with the next annual IB update or study amendment, whichever occurs first.

Report to be submitted via an amendment.

DSMB/IDMC letters, charter, outcomes

Document in format determined by the Sponsor.

Separate submission is not required unless there are updates to the safety risk profile of the study drug which require action and patient notification.

All DSMB/IDMC letters, charters, outcomes should be submitted with the next annual IB update or study amendment, whichever occurs first.

Report to be submitted via an amendment.

Investigator’s Brochure update

Any update/addenda of the Investigator’s Brochure.

Report to HREC within a reasonable timeframe of receipt from the Sponsor submitted via an amendment.

Documents not requiring HREC submission

 
  • Single case AEs, SAE/SARs   and SUSARs (or device/non-therapeutic good trial equivalents)
  • Six monthly line listings

HREC Submission Requirements: Serious breaches

In line with the NHMRC guideline Reporting of Serious Breaches of Good Clinical Practice (GCP) or theProtocol for Trials Involving Therapeutic Goods’ guidelines Serious Breach are defined as follows:

“A breach of Good Clinical Practice or the protocol that is likely to affect to a significant degree:

a) The safety or rights of a trial participant, or

b) The reliability and robustness of the data generated in the clinical trial.”

Submission Type

Required details

Timelines and further review

Serious breaches (for MQ University participants only)

Details of the serious breach including the number of participants affected (if applicable), actions taken to protect participants’ safety, rights and welfare and preliminary corrective and preventative action plan (CAPA).

Reported within 7 calendar days of confirming a serious breach has occurred.  Submitted via AE form.

Upon HREC request, submission of follow up reports may be required to inform the HREC of the CAPA outcomes.

Protocol violations (materially impacting data integrity or the safety, rights or welfare of study participants)

Details of the protocol violation including the number of participants affected (if applicable), actions taken to protect participants’ safety, rights and welfare and preliminary corrective and preventative action plan (CAPA).

Reported within 7 calendars of confirming a serious breach has occurred.  Submitted via AE form.

Upon HREC request submission of follow up reports may be required to inform HREC of the CAPA outcomes.

Documents not requiring HREC submission

 

Protocol deviations, that do not meet the definition of a protocol violation, for example:

  • Scheduling a required   procedure outside the timeframe.
  • Missed assessments that   do not impact on participant safety.
  • Repeat or multiple   protocol deviations may meet the definition of a protocol violation if they   impact on data integrity.